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Regenerative Medicine Brochure - Harvard Apparatus

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your strategic partners in developing<br />

physiologically advanced technologies for<br />

<strong>Regenerative</strong><br />

<strong>Medicine</strong><br />

from Research<br />

to Clinical<br />

Applications<br />

Treatment, Preparation &<br />

Harvesting<br />

Engineering & Modification<br />

Culturing & Growth<br />

Physiological Assessment &<br />

Condition Monitoring<br />

Electrophysiology<br />

&<br />

Cell Biology<br />

Research<br />

<strong>Regenerative</strong><br />

<strong>Medicine</strong><br />

Call to receive other catalogs of interest:<br />

Behavioral<br />

Research<br />

<strong>Harvard</strong><br />

<strong>Apparatus</strong><br />

Pumps<br />

Electroporation<br />

&<br />

Electrofusion<br />

Molecular<br />

Sample<br />

Preparation


Table of Contents<br />

<strong>Regenerative</strong> <strong>Medicine</strong><br />

2Table <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

of Contents<br />

Introduction................................................................................................................................................................................................2-5<br />

Overview of Technical Documents................................................................................................................................................................6-9<br />

New Product Summary & Phases ................................................................................................................................................................10-11<br />

Table of Contents for Phases 1-4 ................................................................................................................................................................12<br />

Phase 1: Preparation & Harvesting Overview<br />

Introduction ........................................................................................................................................................................................13-14<br />

Drug Delivery/Infusion, Nanomite Syringe Pump ....................................................................................................................................15<br />

Stem Cell Cooled Injection, NanoCool Delivery System ............................................................................................................................16<br />

Fast Bolus Injection System ..................................................................................................................................................................17<br />

Pulsatile Perfusion, Pulsatile Blood Pump ..............................................................................................................................................18<br />

Electrospinning, Advanced Polymer Mixing Delivery System......................................................................................................................19<br />

Cell Culture Perfusion, PHD ULTRA Push/Pull Syringe Pump ..................................................................................................................20<br />

Pressure Controlled Injection Pump ........................................................................................................................................................21<br />

Complex Mixture/Dose Delivery, PHD ULTRA Gradient System ................................................................................................................22<br />

Accessories: Syringe Warmers ..............................................................................................................................................................23<br />

Accessories: Microfluidic Valves, Circuits, Chips & Tubing ........................................................................................................................24<br />

Ventilators for All Species ......................................................................................................................................................................25<br />

Phase 2: Engineering and Modification Overview<br />

Introduction ........................................................................................................................................................................................26-27<br />

Cellular Gene Delivery Systems ..............................................................................................................................................................27<br />

• Electroporation, Electrofusion, Cell Injection System, Lipsomat-Liposome Production........................................................................27<br />

Phase 2 Examples................................................................................................................................................................................28<br />

• Molecular Biology, Sample Preparation ........................................................................................................................................28<br />

• Protein-Drug Binding Systems ....................................................................................................................................................28<br />

Phase 3: Culturing & Growth Overview<br />

Introduction ........................................................................................................................................................................................29<br />

InBreath 3D Bioreactor for Hollow Organs Bronchus, Trachea & Blood Vessels ..........................................................................................30-31<br />

LB-2 Lung Bioreactor............................................................................................................................................................................32-33<br />

HPC-3, Hydrostatic Perfusion Chamber for Organ and Tissue ..................................................................................................................34<br />

Cell and Tissue Perfusion, Imaging & Assay Chambers ............................................................................................................................35<br />

Toxin and Chemical Compound Removal, FLOW-Thru Dialyzer ..................................................................................................................36<br />

Phase 4: Physiological Assessment & Condition Monitoring Overview<br />

Introduction ........................................................................................................................................................................................37-38<br />

Blood Gas and Ion Measurements, pH, CO 2<br />

, O 2<br />

, & Glucose Probes ..........................................................................................................39-40<br />

Guide for Advanced Metabolic and Physiological Evaluation of Organisms, Organs, Tissues & Cells using IR Contrast Imaging (IR-CI) ............41-43<br />

Visible Light Imaging, Digital Magnification System..................................................................................................................................44<br />

References ................................................................................................................................................................................................45-46<br />

Contact Us..................................................................................................................................................................................................47<br />

Note: For Research Use Only. Not for use in humans unless proper investigational device regulations have been followed.<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


<strong>Harvard</strong> Bioscience companies have partnered<br />

with leading global scientists to provide specialized<br />

solutions for 110 years… and we are doing it again!<br />

<strong>Harvard</strong> <strong>Apparatus</strong><br />

and the <strong>Harvard</strong><br />

Bioscience family<br />

of companies are<br />

uniquely positioned<br />

to develop advanced<br />

instrumentation to accelerate Tissue Engineering and Cell Therapy<br />

treatments in <strong>Regenerative</strong> <strong>Medicine</strong>. From origins in 1901, <strong>Harvard</strong><br />

Bioscience Companies have worked closely with leading global<br />

researchers across many disciplines to produce clinical and research<br />

equipment with…<br />

– the highest performance<br />

– unmatched quality<br />

– expert support<br />

...necessary to meet the demands of cutting-edge life science techniques.<br />

In keeping with this tradition, we look forward to working with you to<br />

develop and supply the next generation of tools to solve the new challenges<br />

of <strong>Regenerative</strong> <strong>Medicine</strong> from the research lab bench to the patient.<br />

<strong>Harvard</strong> <strong>Apparatus</strong> Provides Equipment and Expertise<br />

for All Phases of <strong>Regenerative</strong> <strong>Medicine</strong> Applications<br />

PHASE 1<br />

PREPARATION<br />

& HARVESTING<br />

Surgical preparation, anesthesia<br />

and ventilation, surgical procedures,<br />

food and drug delivery, animal<br />

and tissue handling, processing<br />

and storage.<br />

PHASE 4<br />

PHYSIOLOGICAL<br />

ASSESSMENT & CONDITION<br />

MONITORING<br />

Validation of growth-phase and<br />

end-stage organ/tissue construct,<br />

Monitoring of organ development<br />

for transplant suitability.<br />

ANIMAL<br />

ORGAN-<br />

TISSUE-CELL<br />

RESEARCH<br />

TRANSITION<br />

Equipment<br />

& Methodologies<br />

HUMAN<br />

ORGAN-<br />

TISSUE-CELL<br />

CLINICAL<br />

PHASE 2<br />

ENGINEERING<br />

& MODIFICATION<br />

Gene delivery and modification,<br />

cell growth, differentiation and<br />

manipulation.<br />

PHASE 3<br />

CULTURING & GROWTH<br />

Scaffold preparation,<br />

decellularizaton and<br />

Recellularization, tissue seeding,<br />

scale-up and growth under<br />

physiological conditions.<br />

Introduction <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 3


Introduction<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

<strong>Harvard</strong> <strong>Apparatus</strong> provides advanced<br />

solutions across the full range of Life Science<br />

& Biomedical Research Techniques Utilized in<br />

<strong>Regenerative</strong> <strong>Medicine</strong><br />

RESEARCH:<br />

COMPOUND SCREENING & DRUG DEVELOPMENT<br />

- Protein-drug and protein-protein affinity assays<br />

- Infusion pumps for drug, anesthesia, or nutritional delivery<br />

- Ion channel and ion transport assays, cellular electrophysiology<br />

- Automated animal feeding stations<br />

- Amino acid analysis<br />

ORGAN FUNCTION MODELING<br />

- Vital sign, Blood Gas and Biopotential Monitoring and Analysis<br />

- Ex-vivo Physiology Workstations<br />

MOLECULAR SAMPLE PREPARATION<br />

- Desalting samples for Mass Spectroscopy analysis of cell signaling molecules<br />

- Isolation of nucleic acid from nuclear membranes<br />

- Trace enrich cell metabolic waste products for ID and eventual removal<br />

CELL ENGINEERING AND GENETIC MODIFICATION<br />

- Electroporation<br />

- Electrofusion<br />

- Pneumatic injection<br />

- Live cell imaging and manipulation<br />

MICROFLUIDICS<br />

- Syringe Pumps with Nanoliter Precision<br />

- Pulsatile Pumps for Physiological Simulation<br />

- Microelectromechanical systems (MEMS)<br />

- Lab-on-a-chip (LOC)<br />

- Micro Total Analysis Systems (µTAS)<br />

TISSUE HARVESTING AND SURGICAL PROCEDURES<br />

- Surgical instruments; operating tables and accessories<br />

SAFETY PHARMACOLOGY<br />

- Isolated organ & tissue perfusion<br />

- Controlled environments for microscope-based screening assays<br />

- Electrophysiological Monitoring<br />

- Telemetric Physiology Monitoring<br />

- Cardiovascular Pressure and Pressure-Volume Analysis<br />

REGENERATIVE MEDICINE AND TISSUE ENGINEERING<br />

- Lung Bioreactor for Rat and Mouse, LB-2<br />

- 3D Bioreactor for Trachea/Bronchus and Blood Vesselsm InBreath<br />

- Organ Decellularization and Matrix/Scaffold Recellularization<br />

- Cell Therapy Injector, NanoCool<br />

- Online Physiological and Metabolic Monitoring<br />

- Equipment for Organ Harvesting, Transport and Transplant<br />

- Anesthesia and Ventilation for Surgery and Recovery<br />

CLINICAL:<br />

- 3D Hollow Organ Bioreactor, InBreath<br />

4<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong> & Tissue Engineering & Cell Therapy<br />

<strong>Harvard</strong><br />

Bioscience<br />

Companies<br />

Phase 1 Phase 2 Phase 3 Phase 4 Phase 5<br />

PREPARATION &<br />

HARVESTING<br />

ENGINEERING &<br />

MODIFICATIONS<br />

CULTURING &<br />

GROWTH<br />

CONDITION<br />

MONITORING<br />

WEBSITE<br />

<strong>Harvard</strong><br />

<strong>Apparatus</strong><br />

Denville<br />

Scientific<br />

Hugo Sachs<br />

Elektronik<br />

Biochrom<br />

Warner<br />

Instruments<br />

Hoefer<br />

BTX<br />

Panlab/<br />

Coulbourn<br />

• Identification<br />

Products<br />

• Ventilators<br />

• Anesthesia<br />

• Surgical Tools<br />

• Infusion Pumps<br />

• Spinner Flasks<br />

• Centrifuge<br />

• Pipetting Systems<br />

• Incubators<br />

• Shakers<br />

• Sterilizers<br />

• Ventilators<br />

• Operating Tables<br />

• Vital Signal Monitors<br />

• Fast Bolus Injections<br />

• Cell Delivery Systems<br />

• Iontophoresis<br />

• Liposome Prep<br />

• Drug Delivery Systems<br />

• Capillary Glass<br />

• Transfection Reagents<br />

• Ligation Kits<br />

• Standards<br />

• Visualization Kits<br />

• DNA Polymerase<br />

• PCR<br />

• Molecular<br />

Spectroscopy<br />

• Protein Analysis<br />

• ds DNA<br />

• Oligonucleotide<br />

Primers<br />

• DNA Melts<br />

• Molecular Analysis<br />

• Amino Acids Analysis<br />

• Cell Imaging<br />

• Molecular Analysis<br />

• Cell Membranes<br />

• Cytoplasm Toxin<br />

Measure<br />

• Cell Signaling<br />

Chemicals<br />

• Blotting<br />

• Electroporation<br />

• Electrofusion<br />

• In-vivo Transfection<br />

• Pneumatic Injection<br />

• 3D Bioreactors<br />

• Toxin & Chemical<br />

Removal<br />

• Perfusion Systems<br />

• Spinner Flasks<br />

• Centrifuges<br />

• Pipetting Systems<br />

• Incubators<br />

• Shakers<br />

• Isolated Organ Baths<br />

• Tissue Baths<br />

• 3D Bioreactors<br />

• Molecular<br />

Spectroscopy<br />

• Media Monitoring<br />

• pH Monitoring<br />

• Spill Sensors<br />

• Perfusion Chambers<br />

• Live Imaging<br />

• Blood Gas<br />

Measurements<br />

• Metabolic Monitoring<br />

• Data Aquisition<br />

and Analysis<br />

• Feedback &<br />

Control Syringes<br />

• Protein Measurements<br />

• ssDNA<br />

• RNA<br />

• Phosphorus<br />

• Enzyme Kinetics<br />

• Electrophysiology<br />

• Cardiopulmonary<br />

Mechanics<br />

• Data Aquisition<br />

and Analysis<br />

• Molecular<br />

Spectroscopy<br />

• Amino Acid Analyzers<br />

• Electrodes<br />

• Amplifiers<br />

• Perfusion Chambers<br />

• Imaging Chambers<br />

• Ion Channel<br />

Monitoring<br />

• Ussing Chambers<br />

• Temperature Control<br />

• Molecular<br />

Sample Preparation<br />

• Electrophoresis<br />

• Affinity<br />

• Ion Exchange<br />

• SEC/GPC<br />

• Filtration<br />

• Dialysis<br />

• Behavioral <strong>Apparatus</strong>:<br />

- Mazes<br />

- Rota Rods<br />

- Treadmills<br />

- Activity Monitors<br />

web:<br />

www.harvardapparatus.com<br />

phone:<br />

+1 508-893-8999<br />

web:<br />

www.denvillescientific.com<br />

phone:<br />

+1 908-757-7577<br />

web:<br />

www.hugo-sachs.de/<br />

phone:<br />

0 76 65 - 92 00-0<br />

web:<br />

www.biochrom.co.uk/<br />

phone:<br />

+44 (0) 1223 423723<br />

web:<br />

www.warneronline.com<br />

phone:<br />

(203) 776-0664<br />

web:<br />

www.hoeferinc.com<br />

phone:<br />

+1 508-893-8999<br />

web:<br />

www.btxonline.com<br />

phone:<br />

+1 508-893-8999<br />

web:<br />

www.panlab.com<br />

phone:<br />

34 934 750 697<br />

web:<br />

www.coulbourn.com<br />

phone:<br />

+1 610-395-3771<br />

Introduction <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 5


Ask about our catalogs,<br />

technical guides, application<br />

notes and bibliographies<br />

Our <strong>Harvard</strong><br />

We have Solutions for<br />

<strong>Harvard</strong> <strong>Apparatus</strong> has the largest global support network of experts, and broadest range of<br />

specialized products to assist you in finding the best solutions for your experimental research.<br />

Technical Documents<br />

For Animal, Organ & Cellular Physiology<br />

and Behavioral Research<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

PHYSIOLOGY<br />

Equipment for virtually any Animal, Organ or Cell Biology<br />

Experiment from animal handling to drug infusion to<br />

physiological monitoring.<br />

BEHAVIORAL<br />

Fully integrated research systems covering a range of<br />

powerful behavioral assays.<br />

For Cell/Tissue Engineering, Imaging and Electrophysiology<br />

MICROSCOPIC LIVE CELL:<br />

IMAGING, INJECTION &<br />

ELECTROPHYSIOLOGY<br />

Amplifiers, imaging,<br />

micromanipulation and perfusion for<br />

the electrophysiological and<br />

neurological sciences.<br />

TRANSFECTION<br />

A comprehensive line of instruments<br />

and accessories for both<br />

electroporation and electrofusion of<br />

mammalian, bacterial, yeast, fungi,<br />

insect and plant cells and tissues.<br />

CELL MODIFICATION<br />

This guide explains Liposomes,<br />

Pneumatic Injection, Iontophoresis,<br />

Electroporation and Mechanical<br />

Injectors.<br />

66<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


<strong>Apparatus</strong> Family:<br />

all <strong>Regenerative</strong> <strong>Medicine</strong> Research Applications<br />

Call 508-893-8999 or email regen@harvardapparatus.com for technical support or to<br />

request a catalog or Technical Application Guide.<br />

Specialized Tools for Model Organisms and Ex-Vivo Physiology<br />

Systems, like the IH-SR for Isolated Heart Perfusion<br />

Technical Documents<br />

MODEL ORGANISMS<br />

Features products used specifically for smaller organisms<br />

including Drosophila, Nematodes, Xenopus and Zebrafish.<br />

Specialized Guides for Bioresearch<br />

EPITHELIAL TRANSPORT<br />

Discusses the theory of operation and<br />

presents the largest collection of<br />

Ussing Systems available.<br />

CELLULAR<br />

ELECTROPHYSIOLOGY<br />

TOOLS<br />

Detailed guide for a range of tools for<br />

cell based electrophysiology assays.<br />

ISOLATED HEART<br />

Detailed system guide for the ultimate ex-vivo perfusion<br />

system for small rodent heart, the IH-SR.<br />

BILAYER WORKSTATION<br />

Focus on the Planar Lipid Bilayer<br />

Workstation as a foundation for drug<br />

screening as well as ion channel<br />

structure and function.<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 77


Ask about our catalogs,<br />

technical guides, application<br />

notes and bibliographies<br />

Our <strong>Harvard</strong><br />

We have Solutions for<br />

<strong>Harvard</strong> <strong>Apparatus</strong> has the largest global support network of experts, and broadest range of<br />

specialized products to assist you in finding the best solutions for your experimental research.<br />

Technical Documents<br />

Advanced Organ, Tissue and Cellular Engineering and Therapy Tools<br />

for <strong>Regenerative</strong> <strong>Medicine</strong><br />

REGENERATIVE MEDICINE<br />

3D Bioreactors for Lung, Trachea/Bronchus & Blood Vessels.<br />

Stem Cell Injection Systems for Fast Bolus Injection,<br />

Pressure-Controlled Fluid Delivery, Active Cooling & Mixing of<br />

Cell Suspensions for Injection, Electrospinning.<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

Smooth High Accuracy Flow, Very High, Very Low<br />

or Physiological Flow Rates<br />

NANO & MICROFLUIDICS, PUMPS & INFUSION<br />

Pulsatile Blood Pumps, Peristaltic Pumps, Syringe Pumps and full line of connectors, tubing and accessories.<br />

88<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


<strong>Apparatus</strong> Family:<br />

all <strong>Regenerative</strong> <strong>Medicine</strong> Research Applications<br />

Call 508-893-8999 or email regen@harvardapparatus.com for technical support or to<br />

request a catalog or Technical Application Guide.<br />

Molecular Biology and Assays, Sample Preparation<br />

and Separations<br />

Technical Documents<br />

1D AND 2D ELECTROPHORESIS, WESTERN BLOT, IMAGING SYSTEMS, PROTEIN BINDING<br />

SYSTEMS, SPE CLEAN-UP, DIALYSIS CLEAN-UP, PCR REAGENTS, INCUBATORS, MIXERS<br />

BIOCHROM: Amino Acid Analyzers, Full Family of Spectrometers<br />

BTX: The In Vivo and In Vitro Experts in Electroporation and Electrofusion<br />

DENVILLE SCIENTIFIC: A Complete Family or PCR, Incubators and Mixers<br />

HOEFER: The Electrophoresis People, Molecular Sample Preparation<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 99


New Product Summay<br />

NEW Systems for <strong>Regenerative</strong><br />

and Tissue Engineering<br />

Our newly developed systems are guided by breakscientists<br />

and surgeons to ensure performance,<br />

Stem Cell Cooled Injection with high viability,<br />

NanoCool Delivery System (p. 16)<br />

Developed in the field, specifically to inject 1 ul to 100 ul of stem cells into live<br />

tissue while maintaining cell viability in an accurate and easy-to-use system.<br />

The NanoCool cools,cells to 18 degrees in the syringe during injections.<br />

Fast Bolus Injection System for rapid, controlled fluid delivery (p. 17)<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

Now a system to deliver pressure-controlled fluid injection to intact organs and<br />

tissues. The system delivers rapid injections while simultaneously monitoring<br />

pressure at the injection site. Measured pressure modulates pump speed for<br />

tight control of delivered injection pulse.<br />

Complex Automatic Mixture/Gradient Delivery & Dosing System (p. 22)<br />

Flow Rate<br />

Stepped<br />

Continuous<br />

Time<br />

Ramped<br />

The <strong>Harvard</strong> <strong>Apparatus</strong> Mixture/Gradient systems allow you to deliver Complex<br />

Mixture and Dosing Protocols by controlling multiple flow streams with variable<br />

% concentration automatically. These serial dilutions or changes are preprogrammed<br />

using easy set-up Pump Methods. Injection can also be initiated<br />

by a triggering event from another device, allowing feedback and control loops<br />

to be easily implemented. For example, a pH sensor could trigger injection of<br />

buffer solution to a mixed drug dose in order to maintain pH at a set level.<br />

InBreathe Hollow Organ 3D Bioreactor, proven through<br />

human transplantation (p. 30-31)<br />

Clinically proven and published bioreactor design used in successful human<br />

transplantation of bronchus. Produced in conjunction with Politecnico Di Milano<br />

and University of Barcelona, the InBreath bioreactor is ideally suited to<br />

regeneration of tubular hollow organs such as trachea/bronchus, blood vessels,<br />

esophagus and intestines.<br />

10 10<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


<strong>Medicine</strong>, Cell Therapy<br />

through research in conjunction with leading<br />

validity and scientific relevance.<br />

Dedicated Lung Bioreactor with online pulmonary monitoring (p. 32)<br />

Proven and published whole organ bioreactor specifically designed in<br />

conjunction with Massachusetts General Hospital for generation of rodent lungs.<br />

Real-time monitoring of respiratory mechanics and Active Ventilation during<br />

growth phase for organ performance validation and successful transplantation.<br />

New Product Summary<br />

Sterilizable pH, CO 2<br />

, O 2<br />

and GLUCOSE SENSORS (p. 39)<br />

Blood gas and metabolite measurements are critical determinants of organ and<br />

tissue viability and performance. These sensors are available in a range of sizes<br />

and configurations as well as bioreactor-integrated forms for online monitoring.<br />

Sterilizable and made of completely inert material, these sensors are ideal for<br />

bioreactor use.<br />

Hand-Held Microscope up to 500X Magnification (p. 59)<br />

<strong>Harvard</strong> <strong>Apparatus</strong> Partners Program<br />

Small, light weight digital microscope for Organ and Tissue preparations,<br />

microsurgery, injection or cannulation. Remotely placed monitor (or PC<br />

Connection) enables simple mounting to bioreactor-based systems.<br />

<strong>Harvard</strong> <strong>Apparatus</strong> is partnering with global scientific partners in academia and<br />

industry to license, co-develop or test device concepts that will accelerate<br />

regenerative medicine, cell therapy and tissue engineering in the research and<br />

clinical marketplace. This proven development model has consistently resulted<br />

in refined, successful and relevant commercial products. For development of<br />

advanced, specialized systems for cell, tissue, organ and in-vivo assays please<br />

contact us. Contact Ron Sostek 508-893-8999 x 1100,<br />

rsostek@harvardapparatus.com<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 11 11


NEW Systems for Advancing <strong>Regenerative</strong><br />

<strong>Medicine</strong> & Tissue Engineering<br />

Phase 1: Treatment,<br />

Preparation & Harvesting<br />

Phase 3: Culturing & Tissue<br />

Growth<br />

Phases<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

1. Identification Products<br />

- Tattoo<br />

- Clips<br />

- RFID<br />

2. Hair Removal Products<br />

3. Surgical Equipment<br />

- Operating Tables & Lights<br />

- Magnification Products<br />

4. Surgical Instruments<br />

- Tools<br />

- Needles<br />

- Sutures<br />

- Catheters<br />

- Sterilization Equipment<br />

5. Anesthesia Equipment<br />

6. Ventilation Equipment<br />

7. Vital-Sign Monitoring<br />

- Capnographs<br />

- Homeothermic Blankets<br />

- Pulse Oximeters<br />

- Blood Pressure<br />

- EKG<br />

- Others<br />

8. Recovery Chambers<br />

9. Infusion Products<br />

- Drug Delivery<br />

- Anesthesia Delivery<br />

- Nutrient Delivery<br />

Phase 2: Engineering &<br />

Modification<br />

1. Cell or Tissue Modification:<br />

In Vivo, In Vitro, Gene Delivery<br />

- Pneumatic Femto Injectors<br />

- Electroporation<br />

- Electrofusion<br />

- Iontophoresis<br />

- Liposomes<br />

- Mechanical Injectors<br />

2. Cell or Tissue Accessories<br />

- Capillary Tubes<br />

- Capillary Pullers<br />

- Capillary Forges<br />

- Homogenizers<br />

- Manipulators<br />

3. Perfusion Chambers<br />

- Imaging Culture Plates<br />

4. Molecular Isolation, Purification Analysis<br />

- Amino Acid Analysis<br />

- Electrophoresis<br />

- Western Blot<br />

- Protein-Ligand Interactions<br />

- Protein-Protein Interactions<br />

- DNA purification Kits<br />

5. Molecular Characterization<br />

- Spectrometers<br />

1. Cell & Tissue Preparation<br />

2. Cell Growth<br />

- Media Infusion Pumps<br />

a. physiological<br />

b. continuous flow<br />

- Imaging Chambers<br />

3. Cell Sorting<br />

- Capillary Glass<br />

- Manipulators<br />

4. Cell Harvesting<br />

5. 3D Organ Bioreactors<br />

6. Spinner Flasks<br />

7. Centrifuges<br />

8. Pipetting Systems<br />

9. Tissue Culture<br />

10. Incubators<br />

11. Shakers<br />

12. Continuous flow pumps<br />

Phase 4: Physiological<br />

Assessment & Condition<br />

Monitoring<br />

Cells<br />

1. Microscopic Imaging & Perfusion<br />

Chambers<br />

2. Microscopic Environmental Controls<br />

3. Electrophysiology Products<br />

4. Condition Monitors<br />

Tissues<br />

5. Isolated Tissue & Perfusion Baths<br />

Organs<br />

6. Lung Regeneration Bioreactor<br />

7. 3D Bioreactors – Hollow Organs<br />

Sensors<br />

8. Ion Sensors<br />

Ammonia, Calcium, Chloride, Ethanol,<br />

Glucose, Lactate, Nitrate, Nitric Oxide,<br />

Nitrite, Peroxide, Potassium,<br />

Sodium, Urea<br />

9. Flow<br />

10. Temperature<br />

11. Pressure<br />

12. Force<br />

13. pH, O 2<br />

, CO 2<br />

12 12<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


PHASE 1: Treatment, Preparation & Harvesting<br />

Introduction to Phase 1 Tools, Equipment<br />

and Systems<br />

Preparation & Harvesting of Cells,<br />

Tissues & Organs<br />

1. Identification Products<br />

- Tattoo<br />

- Clips<br />

- RFID<br />

2. Hair Removal Products<br />

3. Surgical Equipment<br />

- Operating Tables & Lights<br />

- Magnification Products<br />

4. Surgical Instruments<br />

- Tools<br />

- Needles<br />

- Sutures<br />

- Catheters<br />

- Sterilization Equipment<br />

5. Anesthesia Equipment<br />

6. Ventilation Equipment<br />

7. Vital-Sign Monitoring<br />

- Capnographs<br />

- Homeothermic Blankets<br />

- Pulse Oximeters<br />

- Blood Pressure<br />

- EKG<br />

- Others<br />

8. Recovery Chambers<br />

9. Infusion Products<br />

- Drug Delivery<br />

- Anesthesia Delivery<br />

- Nutrient Delivery<br />

Phase 1: Introduction<br />

Phase 1 Catalog and Guides<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

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PHASE 1:<br />

Treatment, Preparation & Harvesting:<br />

An Experimental Example<br />

Phase 1: Experiments<br />

Prepare animal & inject drugs or stems cells<br />

into an organ or tissue to promote regeneration<br />

EXAMPLE: CARDIAC INFARCT AND STEM CELL DELIVERY APPLICATION<br />

EXPERIMENTAL GOAL:<br />

Stem cells are delivered around a cardiac infract (circled). Four to ten injections<br />

of volumes in the 5ul range are delivered. Each injection is delivered over a 3<br />

second period.<br />

INJECT ANESTHESIA:<br />

STEP 1: OPEN CHEST CAVITY<br />

STEP 2: INITIATE INFARCT<br />

STEP 3: INJECT STEM CELLS<br />

STEP 4: CLOSE WOUND AND RECOVERY<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

Step 1<br />

• Hair Clipper<br />

• Micro Vascular<br />

Occluder<br />

• Mouse & Rat ID Tags<br />

• Mouse Ventilator<br />

• Homeothermic Blanket<br />

• Sugical Tools<br />

Step 2, 3 & 4<br />

• Stem Cell Delivery Pump<br />

• Fiber Optic Illuminator<br />

• Rat Ventilator<br />

• Hot Bead Sterilizer<br />

• Capnograph<br />

• Recovery Chamber<br />

• Bag Restrainers<br />

• Magnifying Glasses<br />

14 14<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


NEW Nanomite for Limited Volume Drug Delivery<br />

Hand Held or Stereotaxic Mounted<br />

Superior volume delivery<br />

Nanomite<br />

Figure 1: The blue line above, clearly shows the high accuracy and smooth<br />

flow of the Nanomite injection compared to two optimal hand injections.<br />

Flow ramping injections for optimal<br />

spatial cell delivery<br />

The Nanomite does all the work.<br />

You need only to target the area<br />

of interest and step on the foot<br />

pedal.<br />

• Entire flow method recalled and performed<br />

• High accuracy and precision cell delivery<br />

system from 1.3pl to 100 µl injections with<br />

unmatched performance from up to a<br />

1 ml syringe.<br />

• Can be combined with our micro needles down<br />

to gauge 37.<br />

• Cells dispensed and next injection ready<br />

Features & Benefits<br />

• Light weight makes it ideal for hand-held<br />

stereotaxic injection<br />

• Easy-to-use LCD color touch screen with<br />

GUI interface<br />

• Multiple methods storage makes running<br />

simple or complex methods easy<br />

• High performance in a small package<br />

• Better performance than manual injections<br />

• Version for automatic infusing and withdrawing<br />

• Hand-off injections use foot-pedal activation<br />

Figure 2: Tissue creates backpressure but flow is gently ramped so tissue has<br />

a chance to expand to accommodate liquid displacement. You program a<br />

volume and time to be delivered, Nanomite does the rest.<br />

Specifications<br />

# of Syringes 1<br />

Accuracy ±0.5%<br />

Cable Length 6 ft (1.8 m)<br />

Cable Length<br />

Controller Dimensions 4-1/2 x 9 x 4-1/2 in (11.4 x 22.9 x 11.4 cm) (H x W x D)<br />

Flow Rate Maximum<br />

1900 µl/min<br />

Flow Rate Minimum<br />

3.3 nl/hr<br />

Injector Head/Actuator 7 x 1-3/8 x 2 in (17.8 x 3.5 x 5.1 x cm) (L x H x W)<br />

Pump Function Infusion, withdrawal, volume dispense or continuous pumping modes<br />

Reproducibility ±0.1%<br />

Syringe Diameter (Max) 6.00 mm<br />

Syringe Size<br />

Maximum<br />

1 ml<br />

Minimum 0.5 µl<br />

Syringe Types<br />

1700 , 7000 , 700 and 1000 Hamilton syringes, or any<br />

other syringe manufacturer with known ID in mm<br />

Order # Product<br />

70-3601 Nanomite, Infuse/Withdraw<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

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NEW NanoCool Injector: Fixed 18°C for Optimal<br />

Cell Viability or Drug Delivery<br />

20% increase in survivability, 76% Lower O 2<br />

consumption<br />

rate at 18 vs. 37 degrees Celcius<br />

16NanoCool<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

16<br />

NanoCool Cell Delivery System<br />

• 18˚C syringe and eppendorf<br />

• Flow ramping to reduce injection site blowback<br />

• Programmed methods for automatic recall of<br />

entire cell delivery system. Up to 100 methods<br />

stored for recall<br />

• 2 year warranty. Certified with CE, UL,<br />

CB Scheme<br />

• High accuracy delivery between 1.3 pl/min<br />

to 68ml/min<br />

• Preprogrammed bolus injection mode, just<br />

specify injection size and time of dispense<br />

• Foot pedal start keeps hands free<br />

When injecting stem cells viability<br />

of cells can be a major issue. The<br />

<strong>Harvard</strong> <strong>Apparatus</strong> NanoCool is<br />

the only cooled cell injection<br />

system with optional<br />

cooled and oxygenated vortex<br />

mixer. The injection system and<br />

sample vortex holder are held at<br />

18°C. The cell delivery is totally<br />

integrated in it operation through<br />

the NanoCool’s microprocessor<br />

system: power, temperature<br />

injection volumes and flow<br />

ramping are all controlled by the<br />

NanoCool’s program. Keeping the<br />

cells at 18°C instead of 37°C<br />

reduces O 2<br />

consumption of cells<br />

by an average of 76%. The chart<br />

below shows the different organ<br />

utilization curves.<br />

NanoCool Hand-held<br />

or Stereotaxic<br />

Mounted Injector<br />

Temperature effect on O 2<br />

Consumption by Organ Cell Type<br />

Organ Temperature<br />

Oxygen Change in O 2<br />

Comsuption Consumption<br />

% Change<br />

Kidney 37 to 18 3.7 to 0.9 2.8 75.7<br />

Liver 37 to 18 3.0 to 0.6 2.4 80<br />

Heart 37 to 18 2.4 to 0.7 1.7 70.8<br />

Brain 37 to 18 1.9 to 0.4 1.5 78.9<br />

Muscle 37 to 18) 0.8 to 0.2 0.6 75<br />

Skin 37 to 18 0.4 to 0.1 0.3 75<br />

Specifications<br />

Accuracy ±0.5%<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com<br />

Alarms<br />

Average Linear Force<br />

Syringe Diameter (Max)<br />

Syringe Size<br />

Maximum<br />

End-of Run alarm and over pressure alarm<br />

11 to 12 lbs<br />

6.00 mm<br />

1 ml<br />

Minimum 0.5 µl<br />

Syringe Types<br />

Foot-Pedal<br />

NanoCool Touch<br />

Screen Controller<br />

Figure 1: IR Temperature<br />

Image NanoCool at 18°C.<br />

1700 , 7000 ,700 and 1000 Hamilton syringes, or any<br />

other syringe manufacturer with known ID in mm<br />

Injector Head/Actuator 7 x 1-3/8 x 2 in (17.8 x 3.5 x 5.1 x cm) (L x H x W)<br />

Order # Product<br />

70-3040 NanoCool Injector Infusion/Withdrawal<br />

Programmable Single Syringe


Fast Bolus Injector for Cell Therapy<br />

Figure 1: Bone Marrow Aspiration & infusion Needles<br />

Fast Bolus Injector<br />

Fast Bolus Injector<br />

• Inject a fast bolus of large or small volumes in<br />

a second; up to 12X faster than standard pumps<br />

• The highest accuracy and precision available<br />

• Programmable with multiple methods<br />

• Easy-to-use icon interface<br />

• CE, ETL, CSA, UL and CB scheme Global<br />

compliance<br />

• Delivery from picoliter to hundreds of Ml/min<br />

For delivery of fast infusion or bolus injections into Liver, Kidney or Bone<br />

the Fast Bolus Injector makes it easy. The Fast Bolus Injector can mount a<br />

40 ml syringe or larger and accurately inject 100 nl or 100ul per injection with<br />

the push of a foot pedal. This high linear force pump can pump up to 85<br />

to 433 pounds of force, easily tp inject viscous materials cell suspensions<br />

or pastes.<br />

Also a full selection of research surgical products are available: Bone<br />

aspiration and infusion needles, syringes, surgical equipments,<br />

anesthesia circuits, surgical drapes and sponges, ventilators capnographs and<br />

pulse oximeters, catheters, sutures, bone drill and more.<br />

Bolus Delivery Programming, it is as easy as setting the amount to be delivered<br />

and the time frame you want to deliver i.e 5ul in three seconds.<br />

Human Bone Marrow–Derived Mesenchymal Stem Cells for Intravascular<br />

Delivery of Oncolytic Adenovirus 24-RGD to Human Gliomas, [Cancer Res<br />

2009;69 (23):8932–40] .<br />

Multiple methods can be stored and recalled via touch of a button, making the<br />

Fast Bolus Injector the ultimate, easy to use syringe pump. Methods can be<br />

emailed and downloaded from your PC into the pump. Share a method with a<br />

colleague or duplicate a complex experimental set-up with an e-mailed method.<br />

Figure 2: Bone Marrow Injection Sites.<br />

Specifications<br />

Accuracy ±0.50%<br />

Reproducibility ±0.05%<br />

Syringes (Min./Max.)<br />

Flow Rate:<br />

Display<br />

Minimum<br />

Maximum<br />

Connectors:<br />

0.5 µl / 140 ml<br />

1.56 pl/min using 0.5 µl syringe<br />

215.8 ml/min using 140 ml syringe<br />

4.3" LCD Color Display with Touchpad<br />

Non-Volatile Memory Stores all settings<br />

# Syringes/Pump 2,4,8,10 (1.4 Liters capacity)<br />

Linear Force (Max)<br />

Pusher Travel Rate:<br />

Minimum<br />

Maximum<br />

34 kg (75 lbs) @ 100% force selection<br />

0.18 µm/min<br />

190.80 mm/min<br />

Dimensions 10.16 x 30.48 x 21.59 cm (4 x 8.5 x 12 in) (H x W x D)<br />

Weight<br />

Regulatory Certifications<br />

4.5 kg (10 lbs)<br />

Order # Product<br />

70-3045 Fast Bolus Injector<br />

CE, UL, CSA, CB Scheme, EU RoHS<br />

Figure 3: Catheter placed into right<br />

hepatic vein.<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 17 17


Pulsatile Blood Pump for Generation<br />

of Physiological Flow<br />

Pulsatile Blood Pump<br />

Figure 1: A Novel Culture System Shows that Stem Cells Can be Grown in 3D<br />

and Under Physiologic Pulsatile Conditions for Tissue Engineeringof Vascular<br />

Grafts,Oscar Abilez, et al Journal of Surgical Research 132, 170–178 (2006)<br />

doi:10.1016/j.jss.2006.02.017.<br />

Pressure and Flow Curves Using <strong>Harvard</strong> <strong>Apparatus</strong> Model<br />

1421 Pulsatile Blood Pump in Isolated Perfusion of Left<br />

Lower Lobe of Dog Lung<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

Pulastile Blood Pump<br />

• Pulsatile output truly simulates the ventricular<br />

action of the heart<br />

• Minimal hemolysis<br />

• Models for mice to large animals<br />

• Ideal for moving emulsions, suspensions, and<br />

non-Newtonian fluids such as blood<br />

It truly simulates the pumping action of the heart. It features silicone rubbercovered<br />

heart-type ball valves and smooth flow paths which minimize<br />

hemolysis. Only inert materials like silicone rubber, acrylic plastic, and Teflon<br />

contact the fluid. The pumping head is easy to take apart and reassemble and<br />

can be sterilized.<br />

Outstanding Performance<br />

The pulsatile output closely simulates the ventricular action of the heart. This<br />

action provides physiological advantages in blood flow for perfusion in<br />

cardiovascular and hemodynamic studies. It is ideal for isolated organ<br />

perfusion, whole body perfusion, blood transfers, hydration/dehydration<br />

procedures and blood cellular profile studies.<br />

Pump Mechanism<br />

A positive piston actuator and ball check valves provide the proportioning<br />

action. The product of stroke rate times stroke volume is an accurate indicator<br />

of the flow rate. Positive piston action prevents changes in flow rates,<br />

regardless of variations in resistance or back pressure. The piston always<br />

travels to the end of the ejection stroke, independent of the volume pumped.<br />

The Pump completely empties at each cycle.<br />

Figure 2: Pa = Pulmonary, Artery, Pressure; Pv = Pulmonary, Venous, Pressure;<br />

Qpa = Pulmonary Artery Blood Flow. Istrumentation: Pressure (Statham), Flow<br />

(Blotronex Electromagnetic Flowmeter, Recording (Electronics for <strong>Medicine</strong>.<br />

Note: The above data is supplied through the courtesy of Cardiorespiratory<br />

laboratory Columbia-Presbyterian Medical Center New York, New York, Dr.<br />

Alfred P. Fishman, Director.<br />

Specifications<br />

Accuracy ±0.35%<br />

Reproducibility ±0.05%<br />

Syringes (Min./Max.)<br />

Flow Rate:<br />

Display<br />

Minimum<br />

Maximum<br />

Connectors:<br />

0.5 µl / 140 ml<br />

1.56 pl/min using 0.5 µl syringe<br />

220.97 ml/min using 140 ml syringe<br />

4.3" LCD Color Display with Touchpad<br />

Non-Volatile Memory Stores all settings<br />

# Syringes/Pump 2,4,8,10 (1.4 Liters capacity)<br />

Linear Force (Max)<br />

Pusher Travel Rate:<br />

Minimum<br />

Maximum<br />

34 kg (75 lbs) @ 100% force selection<br />

0.18 µm/min<br />

190.80 mm/min<br />

Dimensions 10.16 x 30.48 x 21.59 cm (4 x 8.5 x 12 in) (H x W x D)<br />

Weight<br />

Regulatory Certifications<br />

4.5 kg (10 lbs)<br />

CE, UL, CSA, CB Scheme, EU RoHS<br />

18 18<br />

Order # Product<br />

55-3305 Pulastile Blood Pump<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


Electrospinning of Novel Scaffold Fiber Materials<br />

Syringe Pump<br />

Polymer<br />

solution<br />

Pipette<br />

Jet<br />

Figure 3: Photograph of a meniscus of<br />

polyvinyl alcohol in aqueous solution showing<br />

a fibre being electrospun form a Taylor cone.<br />

Electrospinning<br />

Taylor cone<br />

High Voltage Supply<br />

Figure 1: Schematic of the Electrospinning setup.<br />

Collector Screen<br />

(Rotating or Stationary)<br />

Figure 4: Advanced<br />

Polymer Mixing<br />

Delivery System<br />

A B C D E<br />

Figure 2: (A) Vessel Scaffold, (B) Scaffold for Muscle, (C) Tissue Scaffold, (D) Bone Scaffold, (E) Organ Scaffolds.<br />

Electrospinning<br />

In 1934, a process was patented by Formhals, wherein an experimental design<br />

was outlined for the production of polymer filaments using electrostatic force.<br />

When used to spin less than 100 micron Fibers to micron fibers, the process is<br />

termed “electrospinning.” The electrospinning method uses a high voltage to<br />

create an electrically charged jet of polymer solution or melt, which then dries<br />

or solidifies to leave a polymer fiber. This is accomplished by first mounting a<br />

syringe into a syringe pump capable of delivering a constant pressure and<br />

smooth flow to a pulled spray nozzle. One electrode is placed into this spinning<br />

solution/melt while the other is placed onto a grounded collector, most often a<br />

metal wire mesh. The driving force is provided by a high voltage source<br />

generating up to 30kV of positive or negative polarity through the electrode<br />

located at the nozzle<br />

tip. When an electric<br />

field is subjected to<br />

the end of the nozzle<br />

tube a charged is<br />

induced on the<br />

surface of the liquid.<br />

A mutual charge<br />

repulsion causes a<br />

force directly<br />

opposite to the<br />

surface tension, such<br />

that as the intensity<br />

of the electric field is<br />

increased, the<br />

hemispherical surface of the fluid at the nozzle tip elongates into a conical<br />

shape known as the Taylor cone. With increasing field, a critical value is<br />

attained when the repulsive electrostatic force overcomes the surface tension<br />

and a charged jet of fluid is ejected from the tip of the Taylor cone. The jet<br />

undergoes a whipping process during which the solvent evaporates and the<br />

remaining charged polymer fiber randomly lays itself on the grounded metal<br />

collecting screen. By adjusting the flow of the fluid from the pump and the<br />

magnitude of the electric field, the spinning rate can be controlled.<br />

Variables:<br />

1. Molecular Weight, Molecular-Weight Distribution and Architecture<br />

2. Solution Properties: Viscosity, Conductivity, Surface Tension<br />

3. Electric Potential, Flow Rate, Collection Screen<br />

4. Distance between capillary and collection screen<br />

5. Ambient Parameters: temperature, humidity, chamber air velocity<br />

6. Motion of the Target Screen (collector) and chamber Air Velocity<br />

The <strong>Harvard</strong> <strong>Apparatus</strong> Family of Pumps is<br />

well-suited for electrospinning:<br />

• Regulatory compliance ensuring electrical<br />

currents do not damage pumps with an option<br />

for a custom grounding cable for added user<br />

protection<br />

• Deliver the smoothest and most accurate flows<br />

so that uniform fibers are created without<br />

droplet formation<br />

• Programmable flow rates with automatic time<br />

control; timed length of spin, optimization<br />

protocols can be created, powerful enough for<br />

viscous solutions, highest accuracy at the<br />

lowest (nanoliter) flow rate range<br />

• Rugged design with 2 year warranty and<br />

global support<br />

Order # Product<br />

70-3007 PHD ULTRA Programmable Syringe Pump<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 19


Continuous Flow for Nutrient Delivery Systems<br />

PHD ULTRA Push-Pull<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

PHD ULTRA Push-Pull<br />

Programmable Syringe Pump<br />

• Compensating Flows<br />

- The control of continuous infusion and<br />

simultaneous withdrawal of liquids while<br />

monitoring fluid levels<br />

• Perfusion Across Tissue Beds<br />

- Directional control of pulseless flow across<br />

a tissue bed using switching valves<br />

• Continuous Flow with High Accuracy and<br />

Smooth Flow<br />

- Pump Any Volume Large or Small with<br />

Smooth, Non Pulsating Flow<br />

• Continuous Accurate Flow for High<br />

Pressure systems<br />

- Unlike peristaltic pumps, syringe pumps can<br />

pump against high pressures<br />

• Easily Sterilized Flow Path<br />

- By replacing syringe and tubing with a<br />

sterilized set, this pump can maintain it’s<br />

sterility<br />

Figure 1: Pressure-driven flow was continous using a programmable push-pull<br />

syringe pump (<strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA). Media was equilibriated with<br />

10% or 21% O 2<br />

in a gas exchanger made with gas-permeable silastic tubing.<br />

The continuous flow pump can provide low pulsation, high accuracy and<br />

precise delivery of flow to any reactor set-up. When you are trying to provide<br />

low shear stress, non pulsing flow during the adhesion step of regeneration of<br />

cell deposition for tissue or organ development, the syringe pump provide the<br />

continuous Flow compensation of a peristaltic, with higher accuracies and<br />

precisions. These flows can be cooled or heated with in –line heaters or<br />

coolers, These pumps have a rugged construction which allows the to work for<br />

long periods of time with high reliability. These pumps come with a two year<br />

warranty as a testament to their durability.<br />

Order # Product<br />

70-3009 PHD ULTRA Push-Pull Programmable Syringe Pump<br />

20<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


Pressure Controlled Injection System<br />

Pressure 1<br />

Pressure 2<br />

Figure 1: Pressure Delivery Injection System<br />

Pressure 3<br />

•Directly measure pressure at site of injection<br />

•Simultaneously measure overall system pressure<br />

•Option for holding injection pressure constant<br />

for defined time period<br />

The system is specifically designed for repeatable, pressure controlled<br />

injections into intact organs. However a wide range of settings and accessories<br />

makes the system appropriate for virtuallly any semi-rigid substrate and certain<br />

hollow-body systems.<br />

Order # Product<br />

Pressure-Controlled Injection System Parameters Controller<br />

77-0000 ML866 POWERLAB 4/304 Channel w/LABCHART Software<br />

to Measure System Pressure after Syringe<br />

72-4496 Research Grade Blood Pressure Transducer,<br />

115VAC/60Hz, with 6 ft cable<br />

Blister Pressure Measurement<br />

72-9845 1F SGL Pres CTH 120 cm No Rep<br />

Syringe Pump Capacity 2X up to 140 ml Syringes Max Flow Rate<br />

with 2X 140 ml Syringes is 3.68 ml/sec per Syringe or 7.36 ml/sec<br />

70-3007 PHD ULTRA I/W Programmable<br />

70-3033 PHD ULTRA Analog Central Imput<br />

Pressure 4 Pressure 5<br />

Figure 2: System components include a syringe pump, injection<br />

pathway, pressure measurement hardware, and data acquisition<br />

and feed back system. Injection parameters are programmed<br />

while pressure is continuously monitored. Real time pressure<br />

feedback modulates syringe pump to keep pressure constant.<br />

Order # Product<br />

Constant Pressure Injection<br />

73-1523 PLUGSYS Minicase Type 609<br />

73-2806 SCP PLUGSYS Servo Control F/Perfusion with Interface<br />

Cable for PHD ULTRA Control<br />

73-0065 TAM-A HSE PLUGSYS Transducer Amplifier Module<br />

Type 705/1, Analog Display<br />

72-9843 Pressure Catheter to Tam Cable<br />

Accessories<br />

72-2673 Y-Connector FLL/FLL/MLL (Rotating), Package of 25<br />

72-14553-WAY FLL-FLL-FLL "T" CONNECTOR, POLYPROPYLENE, PK/25<br />

73-0500 Lab Stand w.Heavy Triangular Base Plate 8 mm OD Rod,<br />

30 cm Long. Also includes Acrylate. Block Clamp (73-0566)<br />

W/8 & 10 mm Opening<br />

72-9523 MLL to MLL Connector<br />

77-0156 Manual Press Cal Kit<br />

Pressure Delivery Injection System <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 21


Complex Mixture/Dose Delivery System<br />

Mixture/Dose Delivery System<br />

Flow Rate<br />

Stepped<br />

Continuous<br />

Ramped<br />

Time<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

Figure 1: Stepped, Continuous, and Ramped gradient.<br />

The new <strong>Harvard</strong> <strong>Apparatus</strong> Syringe Pump Gradient System has the ability to<br />

easily program step and continuous concentration gradients from two or three<br />

solvents (Figure 1). The <strong>Harvard</strong> <strong>Apparatus</strong> syringe pumps are highly published<br />

for their superior flow accuracy and precise flow performance from ul/min to<br />

hundreds of ml/min . Figure 2 shows the shows the flow at 1000 and 500<br />

ul/min. In both stem cell bolus injections and 3D reactor perfusion stream<br />

dosing, the <strong>Harvard</strong> <strong>Apparatus</strong> Gradient systems allows you to automatically<br />

deliver injections fluids or perfusion flow streams that can have variable %<br />

concentration automatically. These serial dilutions or solution changes are<br />

preprogrammed or signaled and initiated by an I/O event. In the case of<br />

injections you could automatically change the amount of cells in every injection<br />

by programming an increase in the concentration of cell solution in each<br />

injection, or by simply selecting a new pre-established method. In perfusions, a<br />

pH probe could signal for a different % composition of the perfusion stream, or<br />

dose a perfusion stream automatically. This could provide more buffering<br />

capacity or adjustment solution to the perfusion stream completely unattended.<br />

This new capability of <strong>Harvard</strong> <strong>Apparatus</strong> syringe pumps to completely deliver<br />

% composition changes automatically with high accuracy and precision flow<br />

provides a new economical tool to advance experiments and eliminate manual<br />

input for complex solution changes.<br />

- Enzyme studies<br />

- Reaction dosing solutions<br />

- Drug infusion experiments<br />

- Nutritional infusion experiments<br />

- Mixing polymer in electrospinning<br />

- Chromatography & FIA systems<br />

Figure 2: 1000 nl/min & 500 nl/min with 250 µl syringe Measured on a Sensirion<br />

Flow Sensor (PHD ULTRA)<br />

Figure 3: The following screen shows the set-up for a gradient.<br />

Order # Product<br />

70-4101 PHD ULTRA Gradient System 1 Master/1 Satellite with Stand<br />

70-4102 PHD ULTRA Gradient System 1 Master/2 Satellites with Stand<br />

70-4106 PHD ULTRA Gradient System 1 Master/1 Satellite without Stand<br />

70-4107 PHD ULTRA Gradient System 1 Master/1 Satellite without Stand<br />

22<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


Accessories<br />

Syringe and In-Line Temperature Controllers<br />

Specifications<br />

Heater Resistance<br />

Voltage Requirement<br />

18 Ω<br />

Variable to 12 V maximum<br />

Temperature Range Ambient to 65°C<br />

Temperature Accuracy<br />

Cable Length<br />

Warranty<br />

Syringe warmer<br />

mounted on a<br />

support stand<br />

Syringe warmer on<br />

a syringe pump<br />

SWS-10, SWS-60 & SWS–140<br />

Syringe Warmers<br />

• Independent temperature control for<br />

individual syringes<br />

• Designed for use on a syringe pump<br />

or support stand<br />

• Accommodates 10, 60 and 140 cc syringes<br />

• Scale marking ports permit volume<br />

monitoring during use<br />

• Can be powered from 12 volt battery for<br />

sensitive electrophysiology applications<br />

±1°C<br />

2.4 m<br />

One year<br />

Syringe Warmer Model Specifications<br />

Model Weight Length OD ID Syringe Type<br />

SWS-10 32.7 g 38.2 mm 22.2 mm<br />

SWS-60 76 g 83.7 mm 35.0 mm<br />

Order # Model Product<br />

16.2 mm<br />

Dickerson<br />

29.1 mm<br />

Dickerson<br />

64-1584 SWS-10 Syringe Heater for 10 cc Syringes<br />

64-1560 SWS-60 Syringe Heater for 60 cc Syringes<br />

64-1585 SWS-140 Syringe Heater for 140 cc Syringes<br />

64-1545 TC-124A Temperature Controller, 120 VAC US<br />

64-1545E TC-124AE Temperature Controller, 240 VAC Europe<br />

64-1655 TC-144 Temperature Controller<br />

64-1606 BAC-1 Battery Adapter Cable<br />

Becton<br />

Becton<br />

SWS-140 192 g 109.5 mm 51.0 mm 41.4 mm Monoject<br />

SC-20 Dual In-line Solution<br />

Heater/Cooler<br />

• Heats and cools from 0° to 50°C<br />

• Compatible with Warner Series 20 Chambers<br />

• Optimized for use with the CL-100 Bipolar<br />

Temperature Controller<br />

In-line solution heating has proven to be one of the most effective methods of<br />

maintaining the temperature of perfusion solutions. The SC-20 Dual In-line<br />

Solution Heater/Cooler utilizes Peltier thermoelectric devices to regulate<br />

temperature both above and below ambient levels.<br />

The SC-20 is designed to thermally regulate one or two solutions at the same<br />

temperature. Solution temperature can be maintained at 0°C at flow rates of 2<br />

ml/min., 5°C at 5 ml/min., or as high as 50°C at 5 ml/min.<br />

An integral water jacket is used to remove excess heat from the SC-20 peltier<br />

device. Running water either from a tap or a large reservoir can be used. Flow<br />

rates as low as 4 liters per hour are sufficient to maintain cooling efficiency.<br />

The SC-20 can be used with either one or two discrete perfusate solutions, or<br />

with a solution/gas combination. When coupled with a PHC Series Imaging<br />

Chamber Heater/Cooler Jacket, the SC-20 provides an effective means of<br />

temperature control in a Warner chamber, even in the absence of solution flow.<br />

Each SC-20 is supplied with a TA-29 Thermistor Cable Assembly for monitoring<br />

the bath temperature during use, 10 feet of PE-160 tubing and 10 feet of 1/8" I.D.<br />

x 1/4" O.D. Tygon tubing.<br />

Specifications<br />

Minimum Temperature 0°C (2 ml/min. max flow)<br />

Maximum Temperature 50°C<br />

Maximum Flow Rate at 5°C 5 ml/min.<br />

Accuracy<br />

±0.1°C<br />

Internal Dead Volume 330 µl<br />

Perfusion Lines<br />

Type 316 Stainless Steel, 0.032 in ID x 0.062 in OD<br />

Water Jacket Ports<br />

Type 316 Stainless Steel, 0.12 in ID x 0.147 in OD<br />

Controller<br />

Model CL-100 Bipolar Controller<br />

Physical Dimensions:<br />

Body (D x L)<br />

21 x 165 mm<br />

Weight<br />

109 g<br />

Cable Length<br />

1.9 m<br />

Connector Type<br />

15 pin Male “D”<br />

Warranty<br />

One year<br />

Order # Model Product<br />

64-0353 SC-20 Solution Heater/Cooler Two Line<br />

64-0352 CL-100 Bipolar Temperature Controller<br />

Replacement Parts<br />

64-0107 TA-29 Cable with Bead Thermistor for Heater Controllers<br />

Accessories <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 23


Accessories<br />

Micro Valves & Micro Connectors<br />

Accessories<br />

Valves/Controllers<br />

(Fluids & Pressure) & Glass<br />

or Plastic Fluidic Chips<br />

In-Line PEEK cartridge for<br />

Toxic removal<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

• Fast<br />

• Cost-effective<br />

• Preparation of microfluidic volumes<br />

Until now, commercially available options for preparing microliter volumes have<br />

suffered major drawbacks, including high back pressure, clogging, leakage and<br />

limited surface chemistry options. New CapTite cartridges offer customizable<br />

packing and re-use, for easy sample preparation in both prototypes and highthroughput,<br />

automated systems.<br />

Micro Fluidic Circuits & Chips<br />

• Compact components for 360 µm, 1/16,<br />

and 1/32 inch in tubing<br />

• Fast, breadboard-based design<br />

• Leak-free high pressure setups<br />

Routing fluids can be one of the most time-consuming tasks of microfluidics<br />

research. CapTite microminiature components take the pain out of<br />

constructing setups. Based on components developed by Sandia National<br />

Laboratories, these compact components for 360 µm and 1/16 in tubing are<br />

designed for leak-free connectivity, even at high pressures.<br />

Manifold/Connectors,<br />

Needles & Tubing<br />

Tubing, Connectors and Manifolds<br />

<strong>Harvard</strong> <strong>Apparatus</strong> has a wide range of tubing, connectors and manifolds so<br />

you can create the fluid pathway to meet your specific requirements. We offer<br />

many types of tubing of different materials and sizes. Our fluid manifolds start<br />

at 2 channels and go all the way up to 24 channels. We have a multitude of<br />

connectors that allow you to complete the fluid connections and complete your<br />

system. Please call our technical support staff for additional information.<br />

Microfluidic Construction Kit<br />

Qty Order # Model Product<br />

Single User Kit<br />

72-0426 C360-KIT1 Microfluidic Construction Single User Kit<br />

for 360 µm capillary tubing<br />

Kit Components: Includes Tools A, B, C, D, E (1 each)<br />

75 72-0431 C360-100 One-Piece Fitting<br />

10 72-0433 C360-101 Plug<br />

5 72-0438 C360-203 Tee Interconnect<br />

5 72-0443 C360-204 Cross Interconnect<br />

10 72-0449 C360-300 Luer-Lock Adapter<br />

25 72-0448 C360-400 Bonded Port Connector<br />

2 72-0445 C360-500 Selector Valve<br />

2 72-0430 LS-600 Breadboard<br />

Interface Kit<br />

72-0427 C360-KIT2 Microfluidic Construction Interface Kit for<br />

360 µm capillary tubing<br />

Kit Components: Includes Installation Tools A, B, D, E (1 each)<br />

50 72-0431 C360-100 One-Piece Fitting<br />

5 72-0433 C360-101 Plug<br />

5 72-0438 C360-203 Tee Interconnect<br />

5 72-0443 C360-204 Cross Interconnect<br />

10 72-0449 C360-300 Luer-Lock Adapter<br />

2 72-0445 C360-500 Selector Valve<br />

2 72-0430 LS-600 Breadboard<br />

24<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


<strong>Harvard</strong> <strong>Apparatus</strong> Ventilators & Anesthesia<br />

The World’s Most Published Ventilation Systems for<br />

Stem Cell Harvesting<br />

Look for the complete line of products in the NEW Havard <strong>Apparatus</strong><br />

Animal, Organ and Cell Physiology catalog.<br />

• ANESTHESIA<br />

• CIRCUITS<br />

• SCAVENGERS<br />

• DEWARS<br />

• INFUSION PUMPS<br />

• ANIMAL PREPARATION<br />

TOOLS<br />

• ID SYSTEMS<br />

• HAIR REMOVAL<br />

• RESTRAINERS<br />

• ANIMAL TEMPERATURE<br />

CONTROL<br />

• MAGNIFICATION<br />

PRODUCTS<br />

• OPERATING TABLES<br />

• OPERATING LIGHTS<br />

• RECOVERY CHAMBERS<br />

• SURGICAL TOOLS<br />

Minivent for Mice<br />

Inspira for Mice up to Cats<br />

683 for Mice & Rats<br />

• SUTURES AND NEEDLES<br />

• SCAPELS<br />

• FORCEP<br />

• STERILZERS<br />

• VITAL SIGN MONITORS<br />

• BLOOD FLOW<br />

• CAPNOGRAPH<br />

• EEG<br />

• GLUCOSE<br />

• HEART RATE<br />

• O 2<br />

• OXIMETERS<br />

• pH<br />

• PULSE RATE<br />

• TEMPERATURE<br />

Accessories <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

Anesthesia Machine<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 25


PHASE 2: Engineering & Modification<br />

Phase 2: Introduction<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

Introduction to Phase 2 Tools, Equipment<br />

and Systems<br />

Cell, Tissue Engineering, Modification,<br />

Preparation & De-Cellularization<br />

1. Cell or Tissue Modification:<br />

In Vivo, In Vitro, Gene<br />

Delivery<br />

- Pneumatic Femto Injectors<br />

- Electroporation<br />

- Electrofusion<br />

- Iontophoresis<br />

- Liposomes<br />

- Mechanical Injectors<br />

2. Cell or Tissue Accessories<br />

- Capillary Tubes<br />

- Capillary Pullers<br />

- Capillary Forges<br />

- Homogenizers<br />

- Manipulators<br />

PLI-100A femtoliter cell injector<br />

3. Perfusion Chambers<br />

- Imaging Culture Plates<br />

4. Molecular Isolation,<br />

Purification Analysis<br />

- Amino Acid Analysis<br />

- Electrophoresis<br />

- Western Blot<br />

- Protein-Ligand Interactions<br />

- Protein-Protein Interactions<br />

- DNA purification Kits<br />

5. Molecular Characterization<br />

- Spectrometers<br />

Phase 2 Catalog and Guides<br />

26<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


PHASE 2: Engineering & Modification<br />

<strong>Harvard</strong> <strong>Apparatus</strong> is the Leader in Femoliter to Microliter<br />

Cell Injection & Transfection Products for Optimal Cell and<br />

Tisssue Engineering<br />

PLI-100A: CELL INJECTION SYSTEM<br />

ELECTROPORATION HIGH-THROUGHPUT<br />

IN VIVO, IN VITRO<br />

ASK FOR A<br />

FREE GUIDE<br />

Send email to:<br />

regen@harvardapparatus.com<br />

LIPOSOMAT-LIPOSOME PRODUCTION<br />

ELECTROFUSION & ELECTROPORATION<br />

Phase 2: Introduction <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 27


PHASE 2:<br />

Engineering & Modification,<br />

Application Examples<br />

Phase 2: Examples<br />

A Range of Application Areas for Phase 2<br />

Tools, Equipment and Systems<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

MOLECULAR BIOLOGY<br />

• Electrophoreses (1D,2D)<br />

• Molecular Biological<br />

Sample Prep Tools<br />

- Chromatographic<br />

- Dialysis<br />

- Equilibrium Dialysis<br />

PROTEIN-DRUG BINDING STUDIES<br />

• No Force Flow<br />

• O 2<br />

Pressure CO 2<br />

• pH Calcium Urea<br />

• Temperature, Lactate & More<br />

SAMPLE PREPARATION<br />

• Spectrometers<br />

• HTS Plate Readers<br />

• Amino Acid Analysis<br />

ASK FOR A FREE GUIDE<br />

Send email to:<br />

regen@harvardapparatus.com<br />

28<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


PHASE 3: Culturing & Growth<br />

Introduction to Phase 3<br />

Tools, Equipment & Systems<br />

This section contains systems and tools for the regeneration and growth of engineered or natural scaffolds and cellular<br />

constructs. Complete bioreactor systems typically include one or more growth chambers for the construct as well as fluid<br />

handling pathways for culture media perfusion and cell seeding. Probes for monitoring physiological parameters are typically<br />

included, though these are discussed in more detail among the Phase 4 products.<br />

Cell Culturing & Tissue Growth<br />

1. Cell & Tissue Preparation<br />

2. Cell Growth<br />

- Media Infusion Pumps<br />

a. physiological<br />

b. continuous flow<br />

- Imaging Chambers<br />

3. Cell Sorting<br />

- Capillary Glass<br />

- Manipulators<br />

4. Cell Harvesting<br />

5. 3D Bioreactors<br />

6. Spinner Flasks<br />

7. Centrifuges<br />

8. Pipetting Systems<br />

9. Tissue Culture<br />

10. Incubators<br />

11. Shakers<br />

12. Continuous flow pumps<br />

Phase 1 Catalog and Guides<br />

Phase 3: Introduction <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 29


InBreath 3D Bioreactor for Hollow Organs,<br />

Bronchus, Trachea & Blood Vessels<br />

Proven through Research and Human Clinical Transplantation<br />

InBreath<br />

from the culture compartments. The connection between the motion unit and<br />

the culture chamber allows the first to remain in the incubator for the whole<br />

culture period, moving the chamber independently every time is needed (i.e.<br />

sampling, medium exchange). An external control unit regulates and monitors<br />

rotation. Autoclavability, ease of handling under sterile conditions, reliability<br />

and precision ensure the full compatibility of the device with the GLP rules<br />

(Good Laboratory Practice).<br />

Benefits & Features<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

• Facilitates cell seeding procedures on both<br />

sides of a 3D tubular matrix, ensuring<br />

homogeneous plating<br />

• Proven Design - demonstrated regeneration of<br />

human bronchus and successful human<br />

transplantation with positive clinical outcome;<br />

as recently published by Macchiarini et al<br />

(2008) Clinical transplantation of a tissueengineered<br />

airway, The Lancet, Volume 372,<br />

Issue 9655<br />

• Allow seeding and culturing of different cell<br />

types on either side of the tubular scaffold<br />

• Enhance oxygenation of the culture medium<br />

and mass transport (oxygen, nutrients and<br />

catabolites) between the medium and the<br />

adhering cells<br />

• Stimulates the cells with hydrodynamic stimuli,<br />

favoring the metabolic activity and the<br />

differentiation process<br />

• Allows the achievement and maintenance of<br />

sterility and other criteria of Good Laboratory<br />

Practice (GLP), simplicity and convenience<br />

• Permits the possibility of automation and<br />

scale-up/-out<br />

In Breath is a rotating, double-chamber, bioreactor designed for cell seeding<br />

and culturing on both surfaces of a tubular matrix and includes rotational<br />

movement of the scaffold around its longitudinal axis. A polymeric culture<br />

chamber houses the biologic sample and the medium for the whole culture<br />

period. Cylindrical scaffold holders are constructed with working ends of<br />

different diameters - to house matrices of diverse dimensions - and a central<br />

portion of smaller diameter to expose the luminal surface of the matrix for cell<br />

seeding and culturing. A co-axial conduit links the inner chamber to the<br />

external environment through an appropriate interface at the chamber wall.<br />

This provides access to seed and feed the luminal surface of the construct.<br />

Secondary elements moving with the scaffold holder induce continuous mixing<br />

of the culture medium to increase oxygenation and mass transport. The<br />

cell/matrix construct is moved by a DC motor (0-5 rpm adjustable) separated<br />

Easy-to-use Controller<br />

• Compact design for remote placement<br />

(i.e. outside the incubator)<br />

• The rotational speed can be controlled from<br />

0 to 5 rotations per minute<br />

• Motor overload indicator for safe operation<br />

• CE certified<br />

Purpose-Built Reactor Chamber<br />

(Custom configurations available)<br />

• Reactor container and spindle are made of<br />

Polysulphone, Teflon and 316 Stainless Steel<br />

allowing for:<br />

- sterilization<br />

- chemical inertness<br />

- biological compatibility<br />

- transparent for excellent visualization<br />

• Chamber has quick-fit spindle for easy removal<br />

of the spindle and organ construct for analysis<br />

or dissambly<br />

• Rotating spindle assures even exposure to<br />

nutrient media<br />

• Integrated ports on spindle allow access to<br />

internal (lumen) surface of organ<br />

• Compact dimensions allow placements of<br />

multiple units within standard incubator<br />

• Offset cover allows for oxygenation of sample<br />

by non sheering ambient air contact<br />

• Quick release and disassembly of parts makes<br />

sterilization easy<br />

30<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


InBreath 3D Bioreactor for Hollow Organs,<br />

Bronchus, Trachea & Blood Vessels<br />

(continued)<br />

InBreath<br />

Though it integrates several sophisticated features, the design of the InBreath<br />

is straightforward producing a very effective 3D Bioreactor.<br />

Figure 1: Tissue-specific tissue spindles ensure proper fit to the rotating core<br />

for even exposure to bathing media.<br />

Figure 2: Sealable access port through<br />

the chamber wall creates a conduit to the<br />

hollow-milled tissue spindle enabling<br />

clean access to the bronchial lumen for<br />

seeding, in this case, with endothelial<br />

cells from the host.<br />

Note: Images Courtesy of P. Macchiarini,<br />

University of Barcelona and S Mantero,<br />

Politecnico di Milano<br />

Specifications<br />

Rotational Speed<br />

Diagnostics<br />

Materials<br />

Validation<br />

Power<br />

0 - 5 RPM<br />

Positional Monitoring<br />

Polysulphone, Teflon, 318 Stainless Steel<br />

CE<br />

100 - 240 VAC, 50/60 Hz<br />

Figure 3: The semi-circular<br />

“half pipe” chamber floor<br />

creates a shallow well for<br />

external seeding, |here with<br />

host chondrocytes derived from<br />

bone marrow stem cells of the<br />

host. Mixing posts on the<br />

rotating tissue spindle maintain<br />

cells in suspension for even<br />

deposition on the bronchial<br />

surface. (Figure 3)<br />

Order # Product<br />

73-4145 InBreath 3D Bioreactor for Hollow Organs, Bronchus,<br />

Trachea & Blood Vessels<br />

InBreath <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

References: Macchiarini et al (2008) Clinical transplantation of a tissueengineered<br />

airway, The Lancet, Volume 372, Issue 9655<br />

Note: For Research Use Only. Not for use in humans unless proper<br />

investigational device regulations have been followed.”<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 31


NEW LB-2 Bioreactor for Mouse and<br />

Rat Lung Regeneration<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

LB-2 Bioreactor<br />

LB-2 Bioreactor<br />

For regeneration and respiratory monitoring of Mouse and<br />

Rat Lungs from decellularized scaffolds<br />

Benefits & Features:<br />

• Proven design – demonstrated regeneration of<br />

rat lung with physiological performance and<br />

subsequent transplantation, as recently<br />

published by Ott et al, 2010, Regeneration and<br />

orthotopic transplantation of a bioartificial lung<br />

, Nature <strong>Medicine</strong>, Volume 16 No 8, pgs 927-933<br />

•Active control of both airway ventilation and<br />

vascular perfusion during regeneration<br />

•On-line monitoring of respiratory mechanics and<br />

vascular physiology<br />

•Self-contained bioreactor specially designed for<br />

unique lung physiology<br />

Physiological maintenance and monitoring:<br />

The LB-2 provides an optimal, physiologically relevant environment for organ<br />

growth as well as the ultimate foundation for real-time monitoring of<br />

respiratory mechanics. The complete range of pulmonary monitoring parameters<br />

are fully integrated into the bioreactor to enable physiological monitoring during<br />

organ generation and end-stage validation for transplant.<br />

• Airway Flow<br />

• Airway Pressure<br />

• Intrapleural Pressure<br />

• Tidal Volume<br />

• Filtration Coefficient<br />

• Minute Volume<br />

• pH, pO 2<br />

, pCO 2<br />

• Pulmonary Resistance • Temperature<br />

• Pulmonary Compliance • Lung Weight<br />

• Pulmonary Artery Pressure<br />

• Pulmonary Venous (Left Atrial) Pressure<br />

• Vascular Resistance<br />

The LB-2 represents the evolution of legendary <strong>Harvard</strong> <strong>Apparatus</strong> - Hugo Sachs<br />

Elektronik perfusion technology from acute ex-vivo perfusion to Bioreactor<br />

based Organ Regeneration. Over 60 years of whole organ physiological<br />

perfusion experience are at the core of this first commercially available<br />

bioreactor for Lung Regeneration.<br />

Like all <strong>Harvard</strong> <strong>Apparatus</strong> - Hugo Sachs Elektronik perfusion systems, the LB-2<br />

provides unmatched physiological maintenance and monitoring capabilities<br />

thanks to the patented Solid State Physiological Perfusion Circuit (S2P2C)<br />

technology. In the LB-2, this means rigidly milled pathways, directly into the<br />

Perspex structure, for both vascular perfusion and airway ventilation. The result<br />

is precisely repeatable non-turbulent perfusion and respiration characteristics.<br />

This combined with the naturally excellent thermal properties of Perspex,<br />

creates a system that allows control, maintenance, and monitoring of vascular<br />

and respiratory mechanics during regeneration in a way that is more<br />

physiologically relevant than any conventional bioreactor.<br />

System Accessories:<br />

• Small Animal Ventilator<br />

• Pulsate Blood Pump<br />

• Syringe Pump<br />

• Transducers<br />

• Amplifiers<br />

• Data Acquisition and Analysis<br />

References: Ott et al (2010) Regeneration and orthotopic transplantation of a<br />

bioartificial lung, Nature <strong>Medicine</strong>, Volume 16 No 8<br />

32<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


NEW LB-2 Bioreactor for Mouse and<br />

Rat Lung Regeneration (continued)<br />

The LB-2 is a Complete Lung Bioreactor for all phases of<br />

Lung Regeneration<br />

Phase 1: Decellularization<br />

Figure 1: Perfusion decellularization of whole rat lungs. (a) Photographs of a<br />

cadaveric rat lung, mounted on a decellularization apparatus allowing antegrade<br />

pulmonary arterial perfusion. pa, pulmonary artery; pv, pulmonary vein; tr, trachea;<br />

RUL, right upper lobe; RML, right middle lobe; LL, left lobe. Freshly isolated lung<br />

(left), after 60 min of SDS perfusion (middle), and after 120 min of SDS perfusion<br />

(right). The lung becomes more translucent as cellular material is washed out first<br />

from apical segments, then from the middle segments and finally from the basal<br />

segments.<br />

Phase 4: Transplantation<br />

Figure 3: Orthotopic<br />

transplantation and in<br />

vivo function. (a)<br />

Photograph of left rat<br />

chest after anterior<br />

thoracotomy, left<br />

pneumonectomy, and<br />

orthotopic<br />

transplantation of a<br />

regenerated left lung<br />

construct. Recipient left<br />

pulmonary artery (A),<br />

left main bronchus (B)<br />

and left pulmonary vein<br />

(V) are connected to<br />

regenerated left lung<br />

pulmonary artery (a),<br />

bronchus (b) and<br />

pulmonary vein (v).<br />

White arrowheads, the<br />

recipient’s right lung<br />

(infracardiac and right lower lobe); black arrowheads, the regenerated left lung<br />

construct. (b) Radiograph of rat chest after left pneumonectomy and orthotopic<br />

transplanation of a regenerated left lung constuct. White arrowheads, recipient’s<br />

right lung; black arrowheads, regenerated left lung construct. (c) Results of blood<br />

gas analyses showing decrease in arterial oxygen tension (PaO2) after left<br />

pneumonectomy and partial recovery after orthotopic transplantation of a<br />

regenerated left lung construct. Baseline, single lung, 10 min and 30 min<br />

measurements were obtained with the rat intubated with the extubated and<br />

breathing room air without support of a ventilator. Upper P values compare single<br />

lung ventilation to 5 min, and 30 min time points after transplantation at 5 min,<br />

30 min and 6 h time points after operation. Error bars, s.d.<br />

Phase 2: Regeneration<br />

Phase 3: Validation<br />

Figure 2: In vitro functional testing of regenerated lung constructs. (a)<br />

Photographs of regenerated lung contructs attached to the isolated lung<br />

apparatus) pa, pulmonary arterial cannula; pv, pulmonary venous cannula; tr,<br />

trachea) in expiration (left) and inspiration (right; RUL, right upper lobe; RML, right<br />

middle lobe). (b) Bar graphs showing results of blood gas analyses of pulmonary<br />

venous effluent of native lung, HUVEC- and A549-seeded lung groups showed gas<br />

exchange function; pO2/FiO2 ratio and pCO2 did not differ between native and<br />

H-FLC-seeded lungs. (c) Line chart showing the dynamic pressure/volume<br />

relationship during five respiratory cycles of native, decellularized and regenerated<br />

lungs. Corresponding compliance values (ml/cm H2O/s are shown in boxes. (d) Bar<br />

graph comparing vital capacity of native (black), H-A549-seeded lung (gray) and H-<br />

FLC-seeded, regenerated lung (red). Error bars, s.d.<br />

Order #<br />

Product<br />

73-4213 LB-2 Basic Unit for Lung Bioreactor, Size 2<br />

Note: Images and data courtesy of H. Ott, Massachusetts General Hospital<br />

LB-2 Bioreactor <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 33


HPC-3, Hydrostatic Perfusion Chamber for Organ<br />

and Tissue Decellularization<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

HPC-3<br />

Detergent or enzyme based decellularization of tissues and organs can be a<br />

cumbersome process, with multiple bottles of different solutions all leading to<br />

the tissue through a convoluted tubing network. The HPC-3 is a practical<br />

solution to this problem, adding useful features and enabling standardization of<br />

decellularization protocols for any tissue. Three independent non-heated glass<br />

vessels are mounted on a robust vertical stand to provide the required<br />

hydrostatic perfusion pressure and all required tubing, in appropriate lengths, is<br />

included. Glass vessels and the included Teflon Lids are fully autoclavable.<br />

Order # Product<br />

73-001020 3-Fold Hydrostatic Perfusion Chamber with Stand<br />

34<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


Cell and Tissue Perfusion, Imaging &<br />

Assay Chambers<br />

Universal Coverslip Chamber<br />

Ideal for live cell imaging<br />

experiments and cellular<br />

electrophysiology<br />

The NaviCyte<br />

Diffusion/Ussing<br />

Chamber Systems<br />

The “World Standard” for conducting substance transport studies across<br />

cultured cell monolayers or excised tissue under dynamic conditions.<br />

• Higher Throughput Screening<br />

–Up to 24 Chambers<br />

• Easier to Use than Other Systems<br />

Applications Include:<br />

Drug Delivery<br />

Toxicology<br />

Pharmacokinetics<br />

Metabolic Studies<br />

Transport Studies<br />

Cell & Tissue Perfusion <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 35


Flow Through Devices for Removal of Toxins,<br />

Metabolites or Signaling Products<br />

Imaging Chambers<br />

Now sterilizable, in-line dialysis system to de-toxify 3D bioreactor perfusate.<br />

Take out DMSO, salts, and cell communication signal molecules so you can<br />

keep the 3D bioreactor perfusate in safe limits for organ regeneration<br />

The Flow-Thru DIALYZER is a unique system for the rapid dialysis of sample<br />

volumes from 20 µl to 100 ml. It provides a large surface area for Flow-Thru online<br />

dialysis with minimal sample loss. The entire dialysis unit is made of<br />

Teflon, an inert material, and has two separate serpentine channels<br />

superimposed on each other and separated by a dialysis membrane. The length<br />

of each channel is about 700 mm. Five different chambers are available (20 µl,<br />

75 µl, 150 µl, 300 µl and 600 µl). Chambers of different volumes can also be<br />

superimposed on each other for specific applications.<br />

Flow-Thru DIALYZER & Membranes<br />

A. Regenerated Cellulose MEMBRANES:<br />

1k Da MWCO<br />

2k Da MWCO<br />

5k Da MWCO<br />

10k Da MWCO<br />

25k Da MWCO<br />

Dialysis<br />

Buffer In<br />

Dialysis<br />

Buffer Out<br />

50k Da MWCO<br />

B. Cellulose Acetate MEMBRANES:<br />

100 Da MWCO<br />

Dialysis<br />

Buffer<br />

Chamber<br />

500 Da MWCO<br />

1k Da MWCO<br />

2k Da MWCO<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

Sample<br />

Solution In<br />

Sample<br />

Solution Out<br />

Membrane<br />

(1.2 in x 3.2 in)<br />

Sample<br />

Chamber<br />

5k Da MWCO<br />

10k Da MWCO<br />

25k Da MWCO<br />

50k Da MWCO<br />

100k Da MWCO<br />

C. Polycarbonate MEMBRANES:<br />

0.01 um<br />

0.05 um<br />

0.60 um<br />

Filtration or Solid Phase<br />

Extraction<br />

In-Line PEEK cartridge for Toxic removal<br />

• Fast<br />

• Cost-effective<br />

• Preparation of microfluidic volumes<br />

Until now, commercially available options for preparing microliter volumes have<br />

suffered major drawbacks, including high back pressure, clogging, leakage and<br />

limited surface chemistry options. LabSmith’s new CapTite cartridges offer<br />

customizable packing and re-use, for easy sample preparation in both<br />

prototypes and high-throughput, automated systems.<br />

36<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


PHASE 4:<br />

Physiological Assessement &<br />

Conditioning Monitoring<br />

Introduction to Phase 4<br />

Tools, Equipment & Systems<br />

Monitoring and recording of Physiological and Metabolic parameters, or BIOSENSING, is critical in understanding the viability of<br />

organisms, organs, tissues and cells and is the ultimate determinant of organ validation for transplant.<br />

<strong>Harvard</strong> <strong>Apparatus</strong> has probes and systems for more physiological and metabolic measurements than anyone else.<br />

We have tried to list all of our BIOSENSORS and in the following pages, we have noted some of the newest.<br />

For more details or for a specific request, please contact our technical specialists at regen@harvardapparatus.com.<br />

Cell, Tissue, Organ & <strong>Regenerative</strong> Systems<br />

Condition Monitoring Tools<br />

Cells<br />

1. Microscopic Imaging &<br />

Perfusion Chambers<br />

2. Microscopic Environmental<br />

Controls<br />

3. Electrophysiology Products<br />

4. Cell Condition Monitors<br />

Tissues<br />

5. Isolated Tissue & Perfusion<br />

Baths<br />

Organs<br />

6. Lung Regeneration Bioreactor<br />

7. 3D Bioreactors – Hollow<br />

Organs<br />

Sensors<br />

8. Ion Sensors<br />

Ammonia, Calcium, Chloride,<br />

Ethanol, Glucose, Lactate,<br />

Nitrate, Nitric Oxide, Nitrite,<br />

Peroxide, Potassium, Sodium,<br />

Urea<br />

9. Flow<br />

10. Temperature<br />

11. Pressure<br />

12. Force<br />

13. O 2<br />

; CO 2<br />

Phase 4: Introduction <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

Capnograph<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 37


A Range of <strong>Harvard</strong> <strong>Apparatus</strong> BIOSENSING<br />

Probes are Available for Virtually Any Metabolic or<br />

Physiological Measurement<br />

Biosensing<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

Application Areas<br />

• Respiratory Mechanics<br />

• Cardiovascular Physiology<br />

• Absorption<br />

• Metabolism<br />

• Excretion<br />

• Nutrition<br />

• Electrophysiology<br />

• Biopotentials<br />

• Animal Behavior<br />

• Dosing<br />

Measurement Probes<br />

• Blood Pressure Transducers<br />

• Force Transducers<br />

• Differential Air Pressure Transducers<br />

• Flow Probes<br />

• Capnographs<br />

• Pulse Oxymeters<br />

• Temperature Monitors<br />

• Thermocouples<br />

• ECG Electrodes<br />

• Monophasic Action Potential Electrodes<br />

• Weight Transducers<br />

• Electrical Stimulation Electrodes<br />

• Imaging devices<br />

• Blood Gas Probes, pH, O 2<br />

, CO 2<br />

• Ion & Compound Sensors<br />

- Ammonia<br />

- Calcium<br />

- Chloride<br />

- Ethanol<br />

- Glucose<br />

- Lactate<br />

- Nitrate<br />

- Nitric Oxide<br />

- Nitrite<br />

- pH<br />

- Peroxide<br />

- Potassium<br />

- Sodium<br />

- Urea<br />

• Infrared Motion Detectors<br />

Control Unit<br />

Battery Powered Spill<br />

Sensor System<br />

Spill Sensor Mats with<br />

Connecting Cable<br />

• Protect your microscope<br />

• Audible alarm<br />

• TTL cutoff circuitry<br />

• Compatible with upright and inverted<br />

microscopes<br />

• Easy set up and installation<br />

• Complete system<br />

• Force Measurement<br />

• Digital Microscopy<br />

• Automated Blood Gas<br />

and Temperature<br />

Control<br />

• Air Pressure<br />

• pCO 2<br />

, pO 2<br />

, pH<br />

• Nitrate & Nitrite Ions<br />

• Oxygen levels in<br />

bulk fluids<br />

38<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


NEW Optical Detection of pH, O 2<br />

and CO 2<br />

are<br />

Ideal for Bioreactor Use<br />

Optical Biosensors<br />

• Completely Sterilizable sensors withstand CIP<br />

(Clean-In-Place), SIP (Steam-In-Place), gamma,<br />

and autoclave conditions.<br />

• USP Class VI-certified sensors are shipped precalibrated<br />

although the system allows the user<br />

to perform a simple standardization procedure.<br />

Now pH, O 2<br />

and CO 2<br />

can be measured easily in disposable systems using new<br />

iDots. iDots are welded into the wall of the bioprocess container, are precalibrated,<br />

can be gamma sterilized and are made of all USP Class VI materials.<br />

iDots are readily adaptable to your single-use application using Polestar’s DSP<br />

series optical monitors.<br />

Flow-cell probe is a zero dead-volume sensor that can be up with DSP<br />

series Optical Process Monitors for continuous measurement of DO or pH.<br />

Pre-calibrated DO or pH fluorescent sensing films deposited along the inner<br />

surface of the quartz flow-cell body enabling optical interrogation through the<br />

transparent wall of the flow-cell via standard fiber optic cable. A simple<br />

re-useable clamping device with integral fiber optic connector is provided to<br />

facilitate mounting the device. Flexible silicone tubing on each end of the flowcell<br />

enables quick connection to external tubing or adapters such as Luer-Lock<br />

fittings. All materials used in the construction of the flow-cell sensors are USP<br />

Class VI certified and can withstand autoclave or gamma sterilization.<br />

Puncture probe oxygen sensors are configured for measurements of oxygen in<br />

applications such as package integrity testing, small volume samples and soft<br />

tissue monitoring. The probe is constructed from a small diameter fiber optic<br />

capped with a thin layer of oxygen sensing chemistry fixed within the lumen of<br />

a stainless steel hypodermic needle. Coring and non-coring designs are<br />

available in sizes ranging from 14 gauge to 24 gauge. Responses times (t90) for<br />

Polestar’s puncture probes are


Perfusion Solution Monitor<br />

Universal Perfusion Solution Monitor: proven<br />

electrochemical detection of pH, pO 2<br />

, pCO 2<br />

in<br />

hydrodynamic systems<br />

PH, pO 2<br />

, & pCO 2<br />

System Detail of pH, pO 2<br />

& pCO 2<br />

Sensor System<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

Universal Perfusion<br />

Solution Monitor<br />

• Rugged construction<br />

• Noise free design, no cross talk<br />

• High sensitivity<br />

• Good linearity<br />

For studies involving isolated or in situ perfused organs (heart, lung, liver,<br />

kidney) it is often important to continuously monitor pO 2<br />

, pCO 2<br />

and/or pH of the<br />

perfusate or effluate. Which parameter is measured depends on the organ used<br />

and on the type of experiment conducted.<br />

The universal perfusion solution monitor permits precise continuous or<br />

discontinuous measurement in liquid media of these three key parameters pO 2<br />

,<br />

pCO 2<br />

and pH. The electrodes are all side stream flow-through electrodes and<br />

require a pulsation-free roller pump to deliver constant flow of perfusate<br />

through the electrode at flow rates in the range from 0.5 to 2 ml/min. The<br />

solution is pulled through each of the electrodes in series. The pH sensor<br />

requires an external reference electrode (both the pO 2<br />

and pCO 2<br />

contain<br />

internal reference electrodes). A solid state leak free reference system is used.<br />

Because of the high impedance of these sensors, screening or shielding of the<br />

measuring circuit is required to guard against electrostatic discharges and<br />

other electrical disturbances. The shielding case also provides a convenient<br />

point of attachment to the multi-electrode mounting plate. Sensors are<br />

available individually or configured as a complete package with suitable<br />

amplifiers and Data Aquisition.<br />

Detail of pO 2<br />

Sensor<br />

40<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


Guide for Advanced Metabolic and Physiological<br />

Evaluation of Organisms, Organs, Tissues & Cells<br />

using Infrared Contrast Imaging (IRCI)<br />

Physiological Fluidics Monitoring<br />

Vascularization<br />

Disease Monitoring with Enhanced Visualization<br />

Microscopy <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 41


Guide for Advanced Metabolic and Physiological<br />

Evaluation of Organisms, Organs, Tissues & Cells<br />

using Infrared Contrast Imaging (IRCI) (continued)<br />

Microscopy<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

Know More About Your Experiment with IRCI<br />

<strong>Harvard</strong> <strong>Apparatus</strong> has utilized infrared imaging in a way that not only provides temperature imaging but also produces high contrast images in biological and<br />

medical applications. This new technique uses the camera’s ability to detect IR emmisivity from objects as a function of their surface texture, composition,<br />

temperature, shape and more. This new utilization of infrared imaging has been called IRCI - Infrared Contrast Imaging. This powerful technology can visualize,<br />

with high resolution, experimental conditions based on tissue vascularization, structure or metabolic state.<br />

• Site evaluations for viable or necrotic tissue<br />

• More clearly reveal morphological features of biological substrates<br />

• Track injection flow paths in real time to evaluate injection quality<br />

Accurate Noncontact Infrared Measurement For Visualizing<br />

Physiological, Metabolic and Morphological features with IRCI<br />

To assure accurate noncontact infrared temperature measurement keep in mind the following:<br />

• Distance to Target (Spot) Ratio<br />

• Field of View<br />

• Environmental Conditions<br />

• Ambient Temperatures<br />

• Emissivity<br />

Distance to Target Ratio<br />

The distance controls the energy hitting the detector, the closer the camera the more signal being picked up.<br />

Field-of-view<br />

The array must have the correct lens in front of it to get as much illumination of the emitted light onto as many pixels as possible. When choosing a system the lens<br />

should be selected to give you the proper working distance and the magnification to display the area of interest on as much of the array as possible<br />

Environmental Conditions<br />

Watch for environmental conditions in the working area. Steam, dust, smoke, etc., can prevent accurate measurement by obstructing the unit's optics. Dew point or<br />

the moisture in the air can cause blurring of the image also if you have glass containers or certain plastics they will absorb all the IR energy so they are not<br />

transparent to the IR and you will not be able to see through these. If this happens replace the material with a IR transparent material if possible.<br />

Ambient Temperatures (the surrounding temperature)<br />

If the thermometer is exposed to abrupt ambient temperature differences of 20 degrees or more, allow it to adjust to the new ambient temperature for at least 20<br />

minutes. The camera fixed-mounted sensors are specified for performance within certain ambient temperature ranges. For high ambient temperatures, some<br />

camera’s offers air cooling and water cooling options as well as accessories, such as Thermojacket.<br />

Emissivity<br />

Emissivity is the measure of an object's ability to emit infrared energy. Emitted energy indicates the temperature of the object. Emissivity can have a value from 0<br />

(shiny mirror) to 1.0 (blackbody).<br />

Emissivity Differences Create Contrast with IRCI<br />

IRCI has the ability to enhance contrast of objects based on their emmissivity. There are many features of many different types of samples which may be revealed by<br />

IRCI, making it a particularly useful tool. Some of these features are:<br />

• Surface Texture<br />

• Sample Thickness<br />

• Temperature<br />

• Chemical Composition<br />

• Depth Profile<br />

42<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


Guide for Advanced Metabolic and Physiological<br />

Evaluation of Organisms, Organs, Tissues & Cells<br />

using Infrared Contrast Imaging (IRCI) (continued)<br />

Application Example: IRCI for Evaluation of Stem Cell Injection Site Physiology<br />

Infrared contrast imaging (IRCI) enables clear visizualization of physiological and structural features of living tissue which are otherwise very difficult to detect.<br />

This is demonstrated in a rodent model where cardiac infarct was induced via ligation of the left anterior descending coronary artery (LAD).<br />

Areas of advanced cardiac infarct generally display a faint and localized “paleness” at the epicenter of the infarct, where myocardial injury is greatest and most<br />

pronounced. The images below show, widespread changes in detected emmissivity on the myocardial surface after LAD ligation. What may be partially visible<br />

to an experienced observer using the naked eye, is now readily apparent to even the uninitiated user of IRCI technology. As a result, this technique enables<br />

routine procedures to be done without extensive training and with greater accuracy.<br />

Rat Orientation<br />

Infarct<br />

Area<br />

Handheld Digital Microscope with IR illumination<br />

• Pocket sized 3.5" LCD display/image capture<br />

• Real time image or video<br />

• Storage and playback<br />

• Up to 200X variable magnification<br />

• Built-in 8-Always-On white LEDs lighting (Option near UV light)<br />

• Microscope Resolution 628 x 586<br />

• LCD Screen Resolution 320 x 240<br />

Heart<br />

Infarct<br />

Area<br />

Time Zero to Infarct 30 Seconds After Infarct One Minute After Infarct<br />

Heart<br />

Infarct<br />

Area<br />

Heart<br />

Small, Compact and Powerful<br />

The <strong>Harvard</strong> <strong>Apparatus</strong> T-Series of portable infrared cameras<br />

takes infrared camera ergonomics, weight and ease-of-use to a<br />

new level. Usability is key<br />

Ideal for visualizing changes in vascularization or surface<br />

features of tissue and organs with otherwise low contrast.<br />

Microscopy <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

i40 / i50 / i60<br />

• Economical IR camera for monitoring temperature<br />

IR Microscope<br />

• Imaging of 100 micron area at 3 micron resolution<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 43


Digital Microscopy 0-500X with Integral<br />

Illumination: Small, Powerful and Economical<br />

Microscopy<br />

AM2011<br />

• Handheld Microscope<br />

• 0.3M/Resolution 640x480<br />

• USB 2.0 Output<br />

• 10~200X Various Magnification<br />

• 1/4" Color CMOS<br />

• Built-in 4 white LED’s<br />

AM311SAM311ST<br />

(Micro Touch)<br />

• Handheld Microscope<br />

• 0.3M/Resolution 640x480<br />

• USB 2.0 Output<br />

• 10~200X Various Magnification<br />

• LED on/off controlled by software<br />

• AM311ST with<br />

Trigger Button<br />

AM412N AV/TV output<br />

AM412NT LED On/Off<br />

AM412NZT Polarize<br />

AM412NTL Enhanced WD<br />

AM412MNT Aluminium Alloy<br />

AM412MNTL Aluminium Alloy<br />

• Handheld Microscope<br />

• 0.3M/Resolution 640x480<br />

• AV (Video)/TV Output<br />

• Built-in 8 white LED’s<br />

AM313/313T<br />

• Handheld Microscope<br />

• 0.3M/Resolution 640x480<br />

• USB 2.0 Output<br />

• 10~200X Various Magnification<br />

• Measurement feature include (*)<br />

• Built-in 8 white LED’s<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

AMH-RUT<br />

• Handheld Iris Microscope<br />

• 1.3 MP<br />

• USB 2.0 Output<br />

• Resolution 1280x1024<br />

• USB 2.0<br />

• Built-in 4 white LED’s<br />

• 10x -20x Various Magnification<br />

AM311H Earscope<br />

AMH-EAN AV/TV output<br />

AMH-EUT-V3 Earscope 1.3MP<br />

• Handheld Earscope<br />

• 0.3 MP / 1.3 MP<br />

• USB 2.0 Output / or TV<br />

• 10~50X / 55X~90X Magnification<br />

• Built-in 4/6 white LED’<br />

AMH-N5UT<br />

AMB-DT-U1 USB 5X~37X<br />

• Handheld Iris Microscope<br />

AMB-DT-U2 USB 10X~92X<br />

• 1.3 MP<br />

AMB-DT-T1 AV/TV Polarizer<br />

• Resolution 1280x1024<br />

AMB-DT-T3 AV/TV 10X~92X<br />

• USB 2.0<br />

• Handheld Dental Scope<br />

• Built-in 4 white LED’s<br />

• 0.3 MP (TV) 1.3 MP (USB)<br />

• 500X fixed Magnification<br />

• USB 2.0 Output / or TV<br />

• Various Magnification<br />

• Built-in 8 white LED’<br />

AMK4012-C200<br />

• Handheld Digital Microscope<br />

• Pocket sized 3.5" LCD display/image capture<br />

• Real time image or video Storage and playback<br />

• Up to 200X variable magnification<br />

• Built-in 8-Always-On white LEDs lighting (Option near UV light)<br />

• Microscope Resolution 628x586<br />

• LCD Screen Resolution 320x240<br />

44<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


References<br />

Our extensive references cover all areas of<br />

interest for <strong>Regenerative</strong> <strong>Medicine</strong><br />

APPLICATION GUIDES:<br />

• BILAYER WORKSTATION<br />

• BOLUS INJECTIONS<br />

• CELL INFUSION<br />

• ELECTRODE<br />

• CULTURE DISH FEEDING<br />

• DRUG INJECTIONS<br />

• ELECTROSPINNING SCALFOLDS<br />

• IMAGING<br />

• ISOLATED HEART SYSTEM<br />

• NANOFLUIDICS<br />

• STEM CELL INJECTIONS<br />

• STEM CELL COLLECTION AND HARVESTING<br />

• USSING CHAMBER<br />

• VENTILATING ANIMALS<br />

Sample Research Publications:<br />

1. Spontaneous hair cell regeneration in the mouse utricle following gentamicin ototoxicity ..BIOREACTOR K Kawamoto, M Izumikawa, LA Beyer, GM … - Hearing Research, 2009 - Elsevier... if missing hair<br />

cells can be replaced by a regenerative treatment ... Infusion speed was controlled by a syringe pump (<strong>Harvard</strong> <strong>Apparatus</strong> Inc., Holliston, MA) at the ...<br />

2. <strong>Regenerative</strong> medicine bioprocessing: concentration and behaviour of adherent cell …BIOREACTOR BJH Zoro, S Owen, RAL Drake, C Mason, M … - Biotechnology and Bioengineering, 2009 -<br />

interscience.wiley.com ... Received March 27, 2009; Accepted April 3, 2009 ... for primary cells typical in regenerative medicine. ... vertically onto a syringe Pump (PHD2000, <strong>Harvard</strong> <strong>Apparatus</strong>...<br />

3. Towards microfabricated biohybrid artificial lung modules for chronic respiratory support…BIOREACTOR /Materials KA Burgess, HH Hu, WR Wagner, WJ … - Biomedical Microdevices, 2009 - Springer...<br />

215 McGowan Institute for <strong>Regenerative</strong> <strong>Medicine</strong>, University ... Biomed Microdevices (2009) 11:117–127 121 ... PHD 2000 syringe pump (<strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA ...<br />

4. An automated system for delivery of an unstable transcription factor to hematopoietic stem …BIOREACTOR E Csaszar, G Gavigan, M Ungrin, C Therien, … - Biotechnology and Bioengineering, 2009 -<br />

interscience.wiley.com... Ontario, Canada 7 McEwen Centre for <strong>Regenerative</strong> <strong>Medicine</strong>, University ... ß 2009 Wiley Periodicals, Inc ... a Model 33 Twin Syringe Pump (#553333, <strong>Harvard</strong> <strong>Apparatus</strong>, St ...<br />

5. Three-Dimensional Gel Bioreactor for Assessment of Cardiomyocyte Induction in Skeletal Muscle–Derived Stem Cell… BIOREACTOR KC Clause, JP Tinney, LJ Liu, B … - … Engineering Part C: …,<br />

2010 - liebertonline.com... 16 Issue 3: May 26, 2010 Online Ahead of Print: February 26, 2010 Online Ahead ... Cell SortingAnalysis of Unsorted Muscle-Derived Stem Cells and Muscle-Derived Stem Cell-3DGB. ... 1 Hz,4<br />

ms, 50–100 V, rectangular pulses) using a stimulator (<strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA ...<br />

6. BMI1 sustains human glioblastoma multiforme stem cell renewal…STEM CELL cjb.net [HTML]M Abdouh, S Facchino, W Chatoo, V … - Journal of …, 2009 - neuro.cjb.net... This work revealed that PcG<br />

proteins are required in human GBM to sustain cancer-initiatingstem cell renewal. Materials and Methods. ... The scalp was closed with wound clips (<strong>Harvard</strong> <strong>Apparatus</strong>). Animals were followed daily for development of<br />

neurological deficits. ...<br />

7. In vivo multimodal imaging of stem cell transplantation in a rodent model of Parkinson's disease…STEM CELL J Jackson, C Chapon, W Jones, E Hirani, A … - Journal of neuroscience …, 2009 - Elsevier...<br />

6-Hydroxydopamine (6-OHDA) was injected into the right striatum at a dose of 16 g, in a volume of 4 L at a rate of 1 L/min, using a micropipettor (<strong>Harvard</strong> <strong>Apparatus</strong>, Edenbridge, UK). ...Post-implantation stem cell<br />

localisation was assessed using high-resolution MR images. ...<br />

8. Effects of ischemic preconditioning on regenerative capacity of hepatocyte in the …STEM CELL A Bedirli, M Kerem, H Pasaoglu, O Erdem, E … - Journal of Surgical Research, 2005 - Elsevier... model have<br />

shown that initiation of the regenerative response depends ... and the common bile duct with a microvascular clamp (<strong>Harvard</strong> <strong>Apparatus</strong>, Inc., Hollinston ...<br />

9. Development of microfluidics as endothelial progenitor cell capture technology for …STEM CELL BD Plouffe, T Kniazeva, JE Mayer Jr, SK … - The FASEB Journal, 2009 - FASEB... using a <strong>Harvard</strong> <strong>Apparatus</strong><br />

PHD 2000 syringe pump (<strong>Harvard</strong> <strong>Apparatus</strong>, .23 October 2009 ... EPCs are a potential tool in regenerative medicine and likely ...<br />

10. Substantial detrusor overactivity in conscious spontaneously hypertensive rats with …STEM CELL LH Jin, KE Andersson, YH Kwon - Scandinavian Journal of Urology and Nephrology, 2009 -<br />

informaworld.com... 2 Wake Forest Institute for <strong>Regenerative</strong> <strong>Medicine</strong>, Wake ... ISSN 1651-2065 online # 2009 Informa UK ... a micro- injection pump (PHD22/2000 pump; <strong>Harvard</strong> <strong>Apparatus</strong>). ...<br />

11. Tbx3 improves the germ-line competency of induced pluripotent stem cells..STEM CELLS/ Electroporation J Han, P Yuan, H Yang, J Zhang, BS Soh, P Li, SL Lim, … - Nature, 2010 - nature.com... Received<br />

14 February 2009; Accepted 9 December 2009; Published online 7 February 2010. ...analyses, Y. Loon Lee, P. Gaughwin and colleagues from the Stem Cell and Developmental ... Cell fusion by Electro cell manipulator (ECM<br />

2001, BTX <strong>Harvard</strong> <strong>Apparatus</strong>) and incubated ...<br />

12. Pilot study to investigate the possibility of cytogenetic and physiological changes in bio- …SCAFFOLD MATERIALS/ electrospinning H Kempski, N Austin, A Roe, S Chatters, SN … - Regen. Med., 2008<br />

- Future <strong>Medicine</strong>... 3 s -1 (PHD 4400, HARVARD <strong>Apparatus</strong> Ltd., Edenbridge ... Materials for Tissue Engineering & <strong>Regenerative</strong> <strong>Medicine</strong>2,158 ... (2009) Bio-electrospraying embryonic stem cells ...<br />

13. In vivo bone tissue engineering using mesenchymal stem cells on a novel electrospun …SCAFFOLD MATERIALS/ electrospinning M Shin, H Yoshimoto, JP Vacanti - Tissue engineering, 2004 -<br />

liebertonline.com... Q 5 0.1 mL/min, PHD 2000 sy- ringe pump; <strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA ... 2009. Nanostructured polymer scaffolds for tissue engineering and regenerative medicine ...<br />

14. Silk fibroin microtubes for blood vessel engineering…SCAFFOLD MATERIALS nih.gov M Lovett, C Cannizzaro, L Daheron, B … - Biomaterials, 2007 - Elsevier... c Center for <strong>Regenerative</strong> <strong>Medicine</strong>,<br />

Massachusetts General Hospital, <strong>Harvard</strong> Medical School ... the bioreactor using a syringe pump (<strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA ...<br />

15. Quantitative Analysis of Neural Stem Cell Migration and Tracer Clearance in the Rat Brain by MRI…STEM CELL JA Flexman, DJ Cross, LN Tran, T Sasaki, Y Kim, S … - Molecular Imaging and … -<br />

Springer... DOI: 10.1007/s11307-010-0311-3 Mol Imaging Biol (2010) ... morphologically transplanted cell migration in the rat brain and parametrically estimate neural stem cell migration speed. ... the skull) using a<br />

picoliter syringe pump (Pico Plus Syringe Pump; <strong>Harvard</strong> <strong>Apparatus</strong>; Holliston ...<br />

16. Therapeutic effect of genetically engineered mesenchymal stem cells in rat experimental leptomeningeal glioma model. STEM CELL C Gu, S Li, T Tokuyama, N Yokota, H Namba - Cancer letters, 2009 -<br />

Elsevier... Mesencult ® murine mesenchymal stem cell medium) after aspiration by 5 ml syringe connected with 23 G needle ... the subarachnoid space by a 50 µl microsyringe (Hamilton Company, Reno, NV) connected<br />

with a 27 G needle and a microinjector (<strong>Harvard</strong> <strong>Apparatus</strong>, Inc., South ...<br />

16. Magnetosonoporation: Instant magnetic labeling of stem cells… STEM CELL B Qiu, D Xie, P Walczak, X Li, J Ruiz- … - Magnetic …, 2010 - interscience.wiley.com... VC 2010 Wiley-Liss, Inc ... basal medium<br />

(Stemcells Inc., Vancouver, Canada), adding NeuroCult supple- ments for neural stem cell differentiation and ... Using a nanoinjector (<strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA), the left brain hemispheres were locally implanted<br />

with approximately 8 ...<br />

17. A seeding device for tissue engineered tubular structures BIOREACTOR L Soletti, A Nieponice, J Guan, JJ Stankus, WR Wagner … - Biomaterials, 2006 - Elsevier... The tees were connected to a precision<br />

syringe pump (<strong>Harvard</strong> <strong>Apparatus</strong> Inc.,Holliston, MA, USA) outside the chamber by means of hydraulic rotating joints (DeublinCo., Waukegan, IL, USA) and polyvinyl chloride (PVC) tubing. ...<br />

References <strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com 45


References<br />

References<br />

<strong>Harvard</strong> <strong>Apparatus</strong> | Advanced Solutions for <strong>Regenerative</strong> <strong>Medicine</strong><br />

18. A novel culture system shows that stem cells can be grown in 3D and under physiologic pulsatile conditions for tissue engineering of vascular grafts 171.65.102.190….BIOREACTOR [PDF]O Abilez,<br />

P Benharash, M Mehrotra, E … - Journal of Surgical …, 2006 - Elsevier... system that would allow future testing of mechanical, biochemical, and thermal stimuli on stem cell differentiation into ... (B) Photo of the<br />

bioreactor (left) and ... The pulsatile pump was a <strong>Harvard</strong> <strong>Apparatus</strong> Model 1405 (<strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA) modified for computer control...<br />

19. … Bioreactors for Tissue Engineering: A System for Characterization of Oxygen Gradients, Human Mesenchymal Stem Cell Differentiation, and Prevascularization…BIOREACTOR M Lovett, D<br />

Rockwood, A Baryshyan, DL … - … Engineering Part C: …, 2010 - liebertonline.com... A System for Characterization of Oxygen Gradients, Human Mesenchymal Stem Cell Differentiation,and ... Medford, MA 02155. E-<br />

mail: Received: April 19, 2010 Accepted: June 1, 2010. ... syringe pump (Remote PHD Push/Pull Programmable Pump; <strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA ...<br />

20. A Three-Dimensional Gel Bioreactor for Assessment of Cardiomyocyte Induction in Skeletal Muscle–Derived Stem Cells BIOREACTOR KC Clause, JP Tinney, LJ Liu, B … - … Engineering Part C: …,<br />

2010 - liebertonline.com... Activated Cell Sorting Analysis of Unsorted Muscle-Derived Stem Cells and Muscle-Derived Stem Cell-3DGB. MDSC-3D collagen gel bioreactor (MDSC-3DGB) construction ... 1 Hz, 4 ms, 50–100<br />

V, rectangular pulses) using a stimulator (<strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA). ...<br />

21. Fabrication and Characterization of Prosurvival Growth Factor Releasing, Anisotropic Scaffolds for Enhanced Mesenchymal Stem Cell Survival/Growth and Orientation …SCAFFOLD MATERIAL<br />

F Wang, Z Li, K Tamama, CK Sen, J Guan - Biomacromolecules, 2009 - ACS Publications... It has been shown to enhance survival of many cell types including smooth muscle cell, cardiomyocyte, and mesenchymal stem<br />

cell.(21-23) Besides, IGF-1 ... The gelatin/BSA/IGF-1 solution was fed at a rate of 0.2 mL/h by syringe pump A (<strong>Harvard</strong> <strong>Apparatus</strong>) into the inner tubing. ...<br />

22. Fabrication and Characterization of Prosurvival Growth Factor Releasing, Anisotropic Scaffolds for Enhanced Mesenchymal Stem Cell Survival/Growth and Orientation …SCAFFOLD<br />

MATERIALS F Wang, Z Li, K Tamama, CK Sen, J Guan - Biomacromolecules, 2009 - ACS Publications... It has been shown to enhance survival of many cell types including smooth muscle cell, cardiomyocyte, and<br />

mesenchymal stem cell.(21-23) Besides, IGF-1 ... The gelatin/BSA/IGF-1 solution was fed at a rate of 0.2 mL/h by syringe pump A (<strong>Harvard</strong> <strong>Apparatus</strong>) into the inner tubing. ...<br />

23. Porous nanocrystalline silicon membranes as highly permeable and molecularly thin substrates for cell culture …SCAFFOLD MATERIAL AA Agrawal, BJ Nehilla, KV Reisig, TR Gaborski, DZ … -<br />

Biomaterials, 2010 - Elsevier... Received 8 March 2010; accepted 16 March 2010. Available online 15 April 2010. Abstract. ...An open perfusion microincubator (<strong>Harvard</strong> <strong>Apparatus</strong>) was used to maintain cells at 37 °C and<br />

mineral oil was floated on top of the media to minimize evaporation. ...<br />

24. A protocol for the production of recombinant spider silk-like proteins for artificial fiber spinning… SCAFFOLD MATERIAL nih.gov [HTML]F Teulé, AR Cooper, WA Furin, D Bittencourt, EL … - Nature<br />

protocols, 2009 - nature.com... Bacteria have quicker generation times and do not require a very sophisticated laboratory setup,thus reducing time and expenses. Additionally, the production can be easily scaled-up using<br />

bioreactors. ... no. P-259); <strong>Harvard</strong> Pump 11 plus single syringe (<strong>Harvard</strong> <strong>Apparatus</strong>, cat. ...<br />

25. Pressure driven spinning: A multifaceted approach for preparing nanoscaled functionalized fibers, scaffolds, and membranes with advanced materials …SCAFFOLD MATERIAL nisco.ch [PDF]SN<br />

Jayasinghe, N Suter - Biomicrofluidics, 2010 - link.aip.org... Biomicrofluidics 4, 014106 (2010)]. ... glass microslides, while for scanning electron microscopy (SEM) and transmission electron microscopy (TEM), fibers were<br />

collected ... at the lowest possible flow rate allowed by our present syringe pump, (PHD4400, <strong>Harvard</strong> <strong>Apparatus</strong> Ltd., Kent ...<br />

26. Characterization and tensile strength of HPC-PEO composite fibers produced by electrospinning …SCAFFOLD MATERIAL L Francis, A Balakrishnan, KP Sanosh, E Marsano - Materials Letters, 2010 -<br />

Elsevier ... strength of HPC-PEO composite fibers produced by electrospinning, Materials Letters (2010), doi: 10.1016/j ... PEO, Sigma Aldrich, Mw = 10,000) were used as starting precursors to fabricate nano fibers. ... of<br />

250 m and was mounted on a syringe pump (<strong>Harvard</strong> <strong>Apparatus</strong> serial n A ...<br />

27. Tbx3 improves the germ-line competency of induced pluripotent stem cells..STEM CELL/ Electroporation J Han, P Yuan, H Yang, J Zhang, BS Soh, P Li, SL Lim, … - Nature, 2010 - nature.com ... karyotype<br />

analyses, Y. Loon Lee, P. Gaughwin and colleagues from the Stem Cell and Developmental ... h, inactivated feeder cells and fresh media were added, and the culture was then ...2-cell fusion by Electro cell manipulator<br />

(ECM 2001, BTX <strong>Harvard</strong> <strong>Apparatus</strong>) and incubated ...<br />

28. Osteochondral Interface Tissue Engineering Using Macroscopic Gradients of Bioactive Signals …STEM CELLS NH Dormer, M Singh, L Wang, CJ Berkland, MS … - Annals of biomedical …, 2010 -<br />

Springer ... 0090-6964/10/0600-2167/0 © 2010 Biomedical Engineering Society ... There is a growing interest in hUCMSCs as a mesenchymal stem cell source, as they have been ... in a con- trolled manner using<br />

programmable syringe pumps (PHD 22/2000, <strong>Harvard</strong> <strong>Apparatus</strong>, Inc., Holliston ...<br />

29. Engineered Early Embryonic Cardiac Tissue Increases Cardiomyocyte Proliferation by Cyclic Mechanical Stretch via p38-MAP Kinase Phosphorylation …BIOREACTOR nih.gov [HTML]KC Clause,<br />

JP Tinney, LJ Liu, BB Keller, … - … Engineering Part A, 2009 - liebertonline.com ... 1 Hz, 4 ms, and 70–100 V) using a stimulator (<strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA). ... Pasumarthi, KB, Soonpaa, MH, and Field, LJ Myocyte<br />

and myogenic stem cell transplantation in ... A Three-Dimensional Gel Bioreactor for Assessment of Cardiomyocyte Induction in Skeletal Muscle ...<br />

30. Dynamic Seeding of Perfusing Human Umbilical Vein Endothelial Cells (HUVECs) onto Dual-Function Cell Adhesion Ligands: Arg-Gly-Asp (RGD)− Streptavidin and …BIOREACTOR CC Anamelechi,<br />

EC Clermont, MT Novak, WM … - Langmuir, 2009 - ACS Publications... combined a dynamic seeding system with a bioreactor proliferation phase to increase cellular adhesion and proliferation for three-dimensional<br />

polymer ... The dynamic seeding system consisted of a 10 mL syringe mounted on a <strong>Harvard</strong> <strong>Apparatus</strong> pump, infusing cells onto Teflon ...<br />

31. Dynamic Seeding of Perfusing Human Umbilical Vein Endothelial Cells (HUVECs) onto Dual-Function Cell Adhesion Ligands: Arg-Gly-Asp (RGD)− Streptavidin and …BIOREACTOR CC Anamelechi,<br />

EC Clermont, MT Novak, WM … - Langmuir, 2009 - ACS Publications... combined a dynamic seeding system with a bioreactor proliferation phase to increase cellular adhesion and proliferation for three-dimensional<br />

polymer ... The dynamic seeding system consisted of a 10 mL syringe mounted on a <strong>Harvard</strong> <strong>Apparatus</strong> pump, infusing cells onto Teflon ...<br />

32. Regeneration and orthotopic transplantation of a bioartificial lung-BIOREACTOR HC Ott, B Clippinger, C Conrad, C Schuetz, I … - Nature <strong>Medicine</strong>, 2010 - nature.com ... Received 22 December 2009 Accepted<br />

04 July 2010 Published online 13 July 2010 ... black arrowheads), axial (gray arrowheads) and septal (black arrows) elastic fibers in decellularized ...trachea and was placed in a sterile, water-jacketed organ chamber<br />

(<strong>Harvard</strong> <strong>Apparatus</strong>). ...<br />

33. Liver-specific functional studies in a microfluidic array of primary mammalian hepatocytes sbi.org …BIOREACTOR [PDF]BJ Kane, MJ Zinner, ML Yarmush, M Toner - Anal. Chem, 2006... 1. A lowmagnification<br />

micrograph of an entire well is shown in Figure 5. Also on post-seeding day 1, the cell culture medium was ... These syringes were loaded into a programmable pump capable of supporting 10 individual<br />

syringes (PHD2000, <strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA ... Cited by 53 - Related articles - All 9 versions<br />

34. … Bioreactors for Tissue Engineering: A System for Characterization of Oxygen Gradients, Human Mesenchymal Stem Cell Differentiation, and Prevascularization …BIOREACTORS M Lovett, D<br />

Rockwood, A Baryshyan, DL … - … Engineering Part C: …, 2010 - liebertonline.com... Tissue Engineering: A System for Characterization of Oxygen Gradients, Human Mesenchymal Stem Cell Differentiation, and ... the<br />

collagen gel using a programmable syringe pump (Remote PHD Push/Pull Programmable Pump; <strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA ...<br />

35. Simple Modular Bioreactors for Tissue Engineering: A System for Characterization of Oxygen Gradients, Human Mesenchymal Stem Cell Differentiation, and … BIOREACTOR M Lovett, D<br />

Rockwood, A Baryshyan, DL … - … Engineering Part C: …, 2010 - liebertonline.com... tube embedded within the collagen gel using a programmable syringe pump (Remote PHD Push/Pull Programmable Pump; <strong>Harvard</strong><br />

<strong>Apparatus</strong>, Holliston, MA). For oxygen measurements,a custom housing for the bioreactor and oxygen measurement probe was ...<br />

36. Cardiac tissue engineering using perfusion bioreactor systems …BIOREACTOR nih.gov [HTML]M Radisic, A Marsano, R Maidhof, Y Wang, G … - Nature protocols, 2008 - nature.com... only within the<br />

construct, that is, at the construct outlet oxygen concentration stops varying as a function of bioreactor length ... 97063A134), coated with PTFE by Microsurfaces; Stereomicroscope; Sterilization pouches; Syringe pump<br />

(Push/Pull; <strong>Harvard</strong> <strong>Apparatus</strong> or WPI Instruments ...<br />

37. Simple Modular Bioreactors for Tissue Engineering: A System for Characterization of Oxygen Gradients, Human Mesenchymal Stem Cell Differentiation, and … BIOREACTOR M Lovett, D<br />

Rockwood, A Baryshyan, DL … - … Engineering Part C: …, 2010 - liebertonline.com... Medford, MA 02155. E-mail: Received: April 19, 2010 Accepted: June 1, 2010. ... 4 µL/min) of the silk tube embedded within the<br />

collagen gel using a programmable syringe pump (Remote PHD Push/Pull Programmable Pump; <strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA). ...<br />

38. Distribution of NTPDase5 and NTPDase6 and the regulation of P2Y receptor signalling in the rat cochlea nih.gov …BIOREACTOR [HTML]MG O'Keeffe, PR Thorne, GD Housley, SC Robson, … -<br />

Purinergic …, 2010 - Springer... Purinergic Signalling (2010) 6:249–261 251 Page 4. ... Plastic tubing was placed inside the inlet and outlet holes and both tubes were connected to separate Hamilton syringes secured on a<br />

push–pull syringe pump (<strong>Harvard</strong> <strong>Apparatus</strong>, USA). ...<br />

39. Liver-specific functional studies in a microfluidic array of primary mammalian hepatocytes sbi.org…BIOREACTOR [PDF]BJ Kane, MJ Zinner, ML Yarmush, M Toner - Anal. Chem, 2006 -These syringes<br />

were loaded into a programmable pump capable of supporting 10 individual syringes (PHD2000, <strong>Harvard</strong> <strong>Apparatus</strong>, Holliston, MA). ... demonstrated that cocultured primary hepatocytes and fibroblasts in a flat plate<br />

bioreactor were not adversely effected by wall ...<br />

46<br />

phone 508.893.8999 • email regen@harvardapparatus.com • web www.harvardapparatus.com


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complex infusion or anesthesia set-ups, selecting the appropriate surgical equipment, or selecting the best pump for Microdialysis. After purchase we assist in<br />

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UNITED STATES<br />

<strong>Harvard</strong> <strong>Apparatus</strong><br />

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phone 508.893.8999<br />

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fax 508.429.5732<br />

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phone 514.335.0792<br />

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GERMANY<br />

Hugo Sachs Elektronik<br />

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phone 49.7665.92000<br />

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phone 34.934.750.697 (International Sales)<br />

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Attn: Sales Department<br />

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Kent TN8 6HE, United Kingdom<br />

phone 44.1732.864001<br />

fax 44.1732.863356<br />

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phone 508.893.8999, toll-free 800.272.2775<br />

fax 508.429.5732<br />

email regen@harvardapparatus.com<br />

web www.harvardapparatus.com<br />

84 October Hill Road<br />

Holliston, MA 01746<br />

phone 508.893.8999, toll-free 800.272.2775<br />

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