Friday, June 24, 2011 - UC Davis Health System

Friday, June 24, 2011
7:30 AM
Room 1222 and 1204
Education Building
UC Davis Medical Center
Sacramento, CA 95817
Table of Contents
Page
I. Symposium Information 3
II. UC Davis-LLNL Point-of-Care Technologies Center 4
III. Young Investigator Presentation Announcement 4
IV. Registration 4
V. Meeting Schedule 5
VI. Young Investigator Presenters 9
VII. Abstracts 10
VIII. Map – Courtyard Marriott to Education Building 43
IX. Map – UC Davis Health System Visitor Parking Lots 44
X. Map – Sacramento International Airport to Hotel 45
2

MEETING INFORMATION
General Information
Point-of-care testing is defined as medical testing at or near the site of patient care. The Point-of-
Care Technologies Research Network (POCTRN) was created to drive the development of
appropriate point-of-care diagnostic technologies though collaborative efforts that simultaneously
merge scientific and technological capabilities with clinical needs
(www.nibib.nih.gov/Research/POCTRN).
Learning Objectives
At the end of this meeting, attendees will be able to: (1) understand invention, innovation,
patenting, and commercialization processes; (2) identify design considerations that facilitate FDA
licensing and CLIA waiver; (3) address potential pitfalls and elements of success for POC device
investigators, developers, and entrepreneurs; and (4) position POC testing for future pivotal
applications in rural, primary, emergency, critical, and disaster care.
Pre-Meeting YOUTUBE Primer
Pre-meeting presentations are available on the UCD – LLNL POC Technologies Center YouTube
site (www.youtube.com/poctctr). Questions and comments on YouTube regarding presentations
will be addressed at the symposium on June 24 th .
Meeting Location
The meeting will be held at the Education Building in Rooms 1222 and 1204 on the University of
California, Davis Health System (UCDHS) campus in Sacramento, California. The Education
Building is located at the corner of X St and 45 th St, Sacramento, CA 95817.
3

UC DAVIS–LLNL POINT-OF-CARE TECHNOLOGIES CENTER
Established by the National Institute of Biomedical Imaging
and Bioengineering (NIBIB) in 2007, the UC Davis-Lawrence
Livermore National Laboratory (LLNL) Point-of-Care (POC)
Technologies Center and three other funded Centers in the
U.S. develop novel diagnostic devices, testing methods, and
interpretive tools that help eliminate health disparities by
making predictive, preemptive, preventive, and personalized
care accessible to all communities. The UC Davis-LLNL
Center focuses on critical-emergency-disaster care and
fosters educational activities that advance evidence-based
practice in critical care, primary outreach, and low-resource
environments, including global health settings.
Ultimately, these activities will improve the accessibility,
portability, and field robustness of POC testing devices for
hospitals, rural areas, and disaster response sites.
YOUNG INVESTIGATOR PRESENTATION ANNOUNCEMENT
Young investigators were encouraged to submit abstracts reflecting original research work. Thirty-one
abstracts have been selected for poster presentations, six of which have been selected by an external
committee for oral presentations. All abstracts are included in this document. The objective of this
special program component is to encourage the development of young investigators conducting
studies in point-of-care testing research and device commercialization.
Research Topic: Topics relate to original research work involving point-of-care testing that is nearing
or has strong potential for commercialization. Case studies demonstrating product development will be
particularly useful in stimulating audience commentary and facilitating studies in point-of-care testing
research and device commercialization.
Eligibility: Advanced undergraduate students, graduate students, postdoctoral scholars, and other
investigators early in their academic or industry careers were encouraged to submit an abstract for
consideration.
REGISTRATION
Registration is free. To register, please send an email to poctcenter@ucdavis.edu with your:
1. Full name
2. Degree(s)
3. Title(s)
4. Institution(s).
4

MEETING SCHEDULE
CLINICALLY DRIVEN COMMERCIALIZATION:
MOVING TECHNOLOGIES TO THE POINT OF NEED
POINT-OF-CARE TECHNOLOGIES RESEARCH NETWORK (POCTRN)
INTERNATIONAL SYMPOSIUM—7:30 AM-5:00 PM, FRIDAY, JUNE 24, 2011
EDUCATION BUILDING, ROOMS 1222 AND 1204
UNIVERSITY OF CALIFORNIA, DAVIS, MEDICAL CENTER, SACRAMENTO, CALIFORNIA
TIME EVENT
0730 Morning Poster Session at the Lobby
0800 Welcome and Introductions
Dr. Gerald Kost, Director, UCD-LLNL POC Technologies Center
Dr. Belinda Seto, Deputy Director, NIBIB
0810 Accelerating Medical Device Innovation: Opportunities in the University
John Linehan, PhD, McCormick School of Engineering and Applied
Science, Feinberg School of Medicine, Northwestern University
1
0840 Invention, Innovation, and the Patenting Process*
Rajagopal Gururajan, PhD, UC Davis Innovation Access, Davis, CA
0910 Entrepreneurism: Translating Biomedical Technologies from Bench to Business*
Vincent Gau, PhD, Gene Fluidics, Monterey Park, CA
0940 BREAK (20 minutes)
1000 Strategies for Commercialization of POC Devices: Customizing Value
Propositions for Challenging Settings
Kara Palamountain, MBA, Center for Innovation in Global Health
Technologies, Northwestern University, Evanston, IL
1030 Product Development Partnerships: A Model for Diagnostic Development
and Transfer for Low Resource Settings
Ralph Schneideman, Commercialization Officer for Technology, Solutions,
and Diagnostic Projects Program at PATH, Seattle, WA
1100 Pushing POC Devices through the FDA and Licensing Process
Erika Ammirati, RAC, MT, Ammirati Regulatory Consulting
* Also available online at http://www.youtube.com/poctctr
1 Online lecture presented by Dr. David McGee, Director, InnovationAccess, UC Davis
5

MEETING SCHEDULE (CONTINUED)
1130 BRINGING TECHNOLOGIES FROM THE BENCH TO COMMERCIALIZATION
Moderator: Thomas Li, PhD, Senior Director, Head of Asian Pacific
Technology, Hoffmann-La Roche
Panelists: Morning Speakers.
Erika Ammirati, RAC, MT, President, Ammirati Regulatory Consulting
Vincent Gau, PhD, President, Gene Fluidics, Monterey Park, CA
Ed Goldberg, PhD, Principal Scientist, Becton, Dickinson and Co.
Rajagopal Gururajan, PhD, Intellectual Property Officer, InnovationAccess,
University of California, Davis
John Linehan, PhD, Professor, Biomedical Engineering, Northwestern
University
Mark Meister, Vice President, Adaptive Methods, Centreville, VA
Kara Palamountain, MBA, Executive Director, Center for Innovation in
Global Health Technologies, Northwestern University
Ralph Schneideman, Commercialization Officer for Technology, Solutions,
and Diagnostic Projects Program at PATH, Seattle, WA
1200 LUNCH BREAK. Afternoon Poster Session at the Lobby.
1300 Public-Private-Partnerships: From Discoveries in PCR Chemistry to Clinical
Diagnostic Assays: a Brandeis University/Smiths Detection Partnership in
Technology Translation
John Czajka, PhD, Smiths Detection
Arthur Reis, PhD, Brandeis University
1340 YOUNG INVESTIGATORS PRESENTATIONS [7 presentations, 10 min each]
Moderator: Dr. Nam Tran, UCD Professor for the Future Fellow
Lessons Learned from Katrina, Haiti, and Japan: A Challenge for All
Seasons and Point-of-Care Settings!
William Ferguson, University of California, Davis
Ischiban: Stroke Assessment Headband
Pooja Kadambi, University of Cincinnati
6

MEETING SCHEDULE (CONTINUED)
A Microdevice with Integrated Aptasensor for Detecting Cell-Secreted
Cytokines
Timothy Kwa, University of California, Davis
Development of a Microwave-Acclerated Metal-Enhanced Fluorescence
(MAMEF) as a Point-of-Care Assay for Detection
Johan Melendez, University Maryland Point-of-Care Mobile
A Point-of-Care Proviral PCR Test for HIV-1 Detection in Infants
Sally McFall, Northwestern University
Rapid p24 Antigen Test for Point-ofCare Diagnossis of Acute Pediatric HIV
Infection
Arman Nabatiyan, Northwestern University
Technology for Early Detection of Diabetes Mellitus
Wilson To, University of California, Davis
1500 NIBIB COMMERCIALIZATION SUCCESSES
Todd Merchak, NIBIB Extramural Science Program
1515 POCTRN EXPLORATORY PROJECTS [15 min each]
UC Davis – LLNL Point of Care Technologies Center
Surface Acoustic Wave Biosensor for Blood Donor Viral Screening
Richard Larson, MD, PhD, Vice Chancellor for Research, Sr. Associate
Dean for Research, University of New Mexico
R&D, 100 Awardee, 2010 (www.rdmag.com)–most innovative products:
Acoustic Wave Biosensor for Rapid Point-of-Care Medical Diagnosis.
Point-of-Care Center for Emerging Neurotechnologies, University of
Cincinnati
Development of a Point-of-Care Device for Quantification of Bilirubin in
Cerebral Spinal Fluid
Blaine G. Booher, BS, Engineer, Xanthostat Diagnostics Inc.
Center for Point-of-Care Technologies Research for Sexually Transmitted
Diseases, Johns Hopkins University
Atlas Genetics: Progress from Core 2 Technology Development for a POC
Test for Chlamydia
Charlotte Gaydos,Dr PH, Center Director
Center to Advance Point-of-Care Diagnostics for Global Health, PATH,
Seattle, WA
Bernhard Weigl, PhD, Center Director
7

MEETING SCHEDULE (CONTINUED)
1615 FUTURE DIRECTIONS FOR POCT INNOVATION AND COMMERCIALIZATION
Moderator: Steve Miller, MD, PhD, University of California, San Francisco
1700 Adjourn
Panelists: Afternoon Speakers
Lars Berglund, MD, PhD, Director of the Clinical and Translational Science
Center, Associate Dean for Research, Professor, UC Davis School of
Medicine
John Czajka, PhD, MBA, Director, Business Development, Smiths
Detection
Charlotte Gaydos,Dr PH, Professor, Infectious Disease, Medicine, Johns
Hopkins University
Lydia Howell, MD, Chair and Professor, Pathology and Laboratory Medicine,
University of California, Davis
Richard Larson, MD, PhD, Vice Chancellor for Research, Sr. Associate Dean
for Research, University of New Mexico
Todd Merchak, Biomedical Engineer, Extramural Science Program, NIBIB
Thomas Nesbitt, MD, MPH, Associate Vice Chancellor for Strategic
Technologies and Alliances, University of California, Davis
Arthur Reis, PhD, Senior Research Scientist, Brandeis University
Bernhard Weigl, PhD, Principal Investigator, GHDx Center, PATH, Seattle, WA
8

YOUNG INVESTIGATOR PRESENTERS
Lessons Learned from Katrina, Haiti, and Japan: A Challenge for All Seasons and POC Settings!
William Ferguson
Invited Young Investigator Speaker
Recipient of the Best Abstract Award, Critical and Point of Care Testing Division of the American
Association for Clinical Chemistry, Annual Meeting, Atlanta, July 24-28, 2011. Clinical Chemistry
2011; 57:D20.
Research Specialist, UCD-LLNL Point-of-Care Technologies Center
University of California, Davis
Ischiban: Stroke Assessment Headband
Pooja Kadambi
Undergraduate Student, Biomedical Engineering
University of Cincinnati
A Microdevice with Integrated Aptasensor for Detecting Cell-Secreted Cytokines
Timothy Kwa
Graduate Student, Biomedical Engineering
University of California, Davis
A Point-of-Care Proviral PCR Test for HIV-1 Detection in Infants
Sally McFall, PhD
Research Assistant Professor, Biomedical Engineering
Northwestern University
Development of a Microwave-Acclerated Metal-Enhanced Fluorescence (MAMEF) as a Point-of-
Care Assay for Detection
Johan Melendez, MS
Graduate Student, Chemistry and Biochemistry
University of Maryland Baltimore County
Rapid p24 Antigen Test for Point-ofCare Diagnossis of Acute Pediatric HIV Infection
Arman Nabatiyan, PhD, MSc
Research Associate Professor, Biomedical Engineering
Northwestern University
Point-of-care mobile technology for early detection of Diabetes Mellitus
Wilson To
Graduate Student, Pathology and Laboratory Medicine
University of California, Davis
Mapping Point-of-Care Performance Using LS MAD MaxAD Curves
*Nam K. Tran, PhD, MS, FACB
Assistant-Adjunct Professor, Pathology and Laboratory Medicine
University of California, Davis
*Voluntarily declined to present
9

ABSTRACTS
Page Young Investigator Abstract Title
_____ (first author only) . ________________________________________________
12 Barney, Rebecca A sensitive rapid diagnostic test for Chagas disease
13 Boonlert, Wanvisa Determining the Limit of Detection of a Multiplex LATE-PCR
Assay for Near-Patient Evaluation of Critically Ill Patients:
Steps Toward Commercial Implementation
14 Brock, Keith Point-of-Care Curriculum Coordinates Intensive Care,
Emergency Support, and Disaster Response
15 Butler, Joshua Improved Point-of-Care Bilirubin Quantification Using a
Robust Spectral Analysis Algorithm
16 Curtis, Corbin Point-of-Need Preparedness for Hematology, Hemostasis,
and Transfusion Crises Encountered in Critical Care,
Emergencies, and Disasters
17 Dillier, Anna Creation and Validation of an iPhone 4 Application for
Photographic Burn Wound Monitoring
18 Enkhbayar, Enkh-Uchral Environmentally Robust Non-invasive Wireless Vitals
Monitor for Disaster Care Settings
19 Ferguson, William Dynamic thermal and humidity stresses on the performance
of two point-of-care glucose reagent test strips for
emergency and disaster care
20 Gentile, Nicole Point-of-care pathogen detection for critical care and low
resource settings using multiplex linear-after-the-exponential
polymerase chain reaction
21 Kadambi, Pooja Ischiban: Stroke Assessment Headband
22 Kandadai, Madhuvanthi Clot Detection in Brain Phantom Using a Real-Time, Non-
Invasive, Point-of-Care Electromagnetic Sensor
23 Kanoksilp, Anan Point-of-Need Hemoglobin A1c for Evidence-Based
Diabetes Care in Rural Small-World Networks
24 Katip, Pratheep Point-of-Care Testing and Continuous O2 saturation
Monitoring following the Tsunami in the small-world network
of Phang Nga Province, Coastal Thailand
25 Kwa, Timothy A microdevice with integrated aptasensors for detecting cellsecreted
cytokines
26 Kwan, Alice Integrated iPhone Spirometry and Breath Metabolite Device
for Asthma Monitoring
27 Lhote, Marine Demonstrating the Feasibility of Modeling Austere Climatic
Profiles for Simulation of Point-of-Care Testing in Disasters
28 Long, Patrick Rapid Molecular Detection of Influenza A and H275Y
Mutation Conferring Resistance to Oseltamivir
29 Majerus, Steve In vivo demonstration of an implantable bladder pressure
sensor in an ambulatory canine subject
30 McFall, Sally A point-of-care proviral PCR test for HIV-1 detection in
infants
10

ABSTRACTS
Page Young Investigator Abstract Title
_____ (first author only) . ________________________________________________
31 McFall, Sally Advancement toward a POC Influenza Diagnostic Device:
Development of a Laboratory Based Nucleic Acid Extraction
System Utilizing Immiscible Phase Filter Purification
32 Mecozzi, Daniel Profession Specific Needs Assessment
33 Melendez, Johan Development of a Microwave-Accelerated Metal-Enhanced
Fluorescence (MAMEF) as a Point of Care Assay for the
Detection of Neisseria gonorrhoea
34 Nabatiyan, Arman Rapid p24 Antigen Test for Point-of-Care Diagnosis of Acute
Pediatric HIV Infection
35 Ozturk, Meric Increasing Leukemia Treatment Compliance through Social
Networking
36 Sumner, Stephanie Impact of dynamic environmental stress testing on glucose
quality control solution for disaster preparedness
37 Tang, Chloe The benefits of use of point-of-care HIV tests in disaster care
38 To, Wilson Point-of-care mobile technology for early detection of
Diabetes Mellitus
39 Tran, Nam Mapping Point-of-Care Performance Using LS MAD MaxAD
Curves
40 Wennberg, Richard A New Point of Care System to Measure Plasma Bilirubin
Concentration
41 Yu, Jimmy Theory, Principles, and Practice of Optimizing Point-of-Care
Small-World Networks for Emergency and Disaster Care
42 Yu, Jimmy Connecting Point-of-Care Informatics in Emergencies and
Disasters
11

A sensitive rapid diagnostic test for Chagas disease
Barney RS 1 , Barfield CA 1 , Crudder CH 1 , Stevens DS 1 , Yanovsky MJ 2 , Yanovsky J 3
1 PATH, Seattle, WA
2 Fundacion Instituto Leloir, Buenos Aires, Argentina
3 Laboratorio Lemos, Buenos Aires, Argentina
Background
Chagas disease, caused by infection with the parasite Trypanosoma cruzi, is one of the most
significant neglected diseases in the developing world. Untreated Chagas disease can lead to
cardiac and digestive complications, resulting in loss of productivity and ultimately death. Chagas
affects mostly the rural poor who have little access to central infrastructure in the health care
system. Reliable diagnosis of Chagas disease is done mostly by means of tests that necessitate a
laboratory with costly equipment and highly trained technicians. The currently available point of
care tests for Chagas disease have sensitivities less than 95%, which is a critical restriction
because the principal component of a screening campaign is to identify as many infected
individuals as possible.
Methods
PATH, a nonprofit international health agency, in collaboration with Laboratorio Lemos, a privatesector
company in Argentina, has developed a rapid Chagas immunochromatographic strip (ICS)
test which utilizes Lemos’ novel, multi-epitope, recombinant antigen for detection of antibodies to
T. cruzi. This test could be taken into rural areas where Chagas diagnostic tools are most needed.
The PATH Chagas ICS test has been optimized for use with whole blood samples. This affords an
opportunity for simpler point-of-care application, since whole blood is easily obtained by fingerstick
in remote locations. The test is composed of nitrocellulose striped with control and test line
reagents, dried-down detector reagent, and a filter used for plasma separation. The test is run by
adding whole blood, serum, or plasma to the filter; buffer is then added and it is visually
interpreted. To evaluate the test 375 blinded serum samples from Argentina were used. The
samples were run using the PATH Chagas ICS test and an FDA-approved ELISA test (the Ortho
T. cruzi ELISA, Johnson & Johnson).
Results
Compared to the ELISA, the PATH ICS test demonstrated a sensitivity and specificity of 99.5%
and 96.8%, respectively. The test also performed favorably using spiked whole blood samples,
but further testing is necessary.
Conclusion
The results of this evaluation show this test has a promising future for use in the diagnosis of
Chagas disease in low-resource settings.
12

Determining the Limit of Detection of a Multiplex LATE-PCR Assay for Near-
Patient Evaluation of Critically Ill Patients: Steps Toward Commercial
Implementation
Boonlert W a , Gentile NL a , Dillier A a , Bimson DJ a , Williams GV b , Czajka JW b ,
Reis AH
c , Rice L c , Carver-Brown R c , Wangh LJ c , Kost GJ a .
a Point-of-Care Testing Center for Teaching and Research and the University of California
Davis-Lawrence Livermore National Laboratory Point-of-Care Technology Center,
University of California, Davis, California
b Smiths Detection Diagnostics, Edgewood, MD, USA
c Department of Biology, Brandeis University, Waltham, MA, USA
Background. The goal of this study was to determine the limit of detection (LOD) of multiplex linear-after-theexponential
polymerase chain reaction (LATE-PCR) tested with genomic DNA (gDNA). Sepsis represents a
leading cause of death in non-coronary intensive care units. Rapid detection and identification of pathogens
enables appropriate antimicrobial treatment, ultimately improving patient outcomes. LATE-PCR, a novel form
of asymmetric PCR utilizing limiting and excess primers that produce single-stranded DNA, has advantages
over traditional blood culture (BC) by generating faster results and aiding definitive pathogen identification. To
improve patient outcomes, rapid diagnosis and treatment are needed. Implementing molecular diagnostics, into
the hospital workflow to compliment BC will allow swift triage and targeted therapy at the point of care.
Methods. DNA from 12 whole organisms obtained from the American Type Culture Collection (ATCC) was
extracted using a sample preparation protocol (Smiths Detection Diagnostics). Eluted DNA was serially diluted
to concentrations ranging from 10 5 to 10 -2 genome copies/µL and tested in parallel with pure gDNA (ATCC) as
a positive control. DNA will be tested in the presence of known concentrations of extracted human DNA from
whole blood of healthy asymptomatic volunteers using the same multiplex LATE-PCR assay.
Results. The LOD of LATE-PCR ranged from 10 to 1000 copies of gDNA in molecular grade water and is
expected not to exhibit interference when challenged with human DNA extracted from whole blood.
Additionally, LATE-PCR demonstrated multiplexing capabilities when in the presence of both bacteria and fungi
(Figure). LATE-PCR differentiates species (e.g., Enterococcus faecium versus Enterococcus faecalis) by using
the ratio of fluorescence measured at 35°C to that at 55 °C.
Conclusions. Multiplex LATE-PCR demonstrates LOD results potentially useful for rapid diagnosis, a valuable
adjunct to blood culture when diagnosing bacteremia in critically ill patients. This study proves feasibility of an
approach that will aid in
early evidence-based
treatment decisions of
high value at or near the
bedside in critical care.
Figure. Quasar detecting
channel at 670nm for
multiplex—CA, Candida
albicans (blue); EFM,
Enterococcus faecium (green);
and EFS, Enterococcus
faecalis (pink) ATCC gDNA
tested in parallel and full
multiplex: A) The first
derivative of the anneal curve
shows probe annealing to EFM and EFS at the same temperature, but probe annealing to CA at a different temperature; B) The anneal
curve was normalized to 75°C with background subtracted, then the highest peak normalized to one.
Abbreviations: AB, Acinetobacter baumannii; ATCC, American Type Collection Culture; EA, Enterobacter aerogenes; EC,
Enterobacter cloacae; gDNA; Genomic DNA; KO, Klebsiella oxytoca; KP, Klebsiella pneumoniae; MRSA, methicillin resistant
Staphylococcus aureus; NTC, Non template control; PA, Psuedomonas aeruginosa; SA, Staphylococcus aureus; SE, Staphylococcus
epidermidis.
13

Point-of-Care Curriculum Coordinates Intensive Care,
Emergency Support, and Disaster Response
T. Keith Brock, BS; Richard F. Louie, PhD; Nikki Gentile, BS; Deborah Bimson; Jimmy Yu,
BS;
Wanvisa Boonlert, MT, PhD; Adam Longley, MBA; and Gerald J. Kost, MD, PhD, MS, FACP
Point-of-Care Testing Center for Teaching and Research (POCT•CTR)
UC Davis-LLNL Point-of-Care Technologies Center [NIBIB, NIH]
School of Medicine, University of California, Davis
One goal of the UC Davis-LLNL Point-of-Care (POC) Technologies Center is to provide
unique courses of instruction for the POC Coordinator, whoever (e.g., MD, PhD, RN, MT, EMT,
administrator, or public health official) and wherever that person might be. The first course (by GK,
AL, NG, and DB) was developed in 2010-11 in collaboration with Mr. Adam Longley in order to
educate POC Coordinators in low-resource settings outside of Western Europe (WE) and the
United States. This course a) consists of several modules and workshops, b) has been field tested
on a preliminary basis in several countries on different continents, c) is complete and ready for
widespread implementation, and d) features POC instruments designed specifically for challenged
countries outside WE or the USA. The second course focuses on disaster point of care and
represents an exclusive product of the Center. Lectures and workshops aggregate experience: i)
gleaned from the first course, ii) derived from a newly devised crisis standard of care, and iii)
based on original environmental stress research published by Center investigators. Each course
can be taught in convenient components over 2-3 days with facile demonstrations and clear
didactics portable to low-resource settings, primary care, and first responders speaking languages
other than English. Media include PowerPoint Slides, audio/video, and participatory
demonstrations, as well as “Just-In-Time” presentations that will appear on the Center YouTube
web site (http://www.youtube.com/POCTCTR). Fundamentally, a POC device or disposable test
must be used properly to assure accuracy and precision of test results and high predictive values
for caregivers. Hence, Coordinators provide practical implementation and invaluable assistance in
a variety of settings, such as small-world networks of varied terrain, island communities, and
unexpectedly altered disaster situations. Courses have been well received in pilot runs, and
therefore, this program will be expanded and developed more fully as a strategic mission for
enhanced global wellness and preparedness.
14

Improved Point-of-Care Bilirubin Quantification
Using a Robust Spectral Analysis Algorithm
Joshua Butler
Point-of-Care Center for Emerging Neurotechnologies
University of Cincinnati, Cincinnati OH
Subarachnoid hemorrhage (SAH) is a particularly deadly intracranial vascular rupture that can
occur unexpectedly and with early onset. Because of the rapid progression of the dangerous
neurological events following an SAH, an immediate detection and quantification of blood species
in the cerebrospinal fluid (CSF) is often necessary to make a reliable SAH or exclusion to
minimize the time to treatment and maximize the chances of recovery. [1]
Recently a point-of-care device called the Bilibox (Xanthostat, Cincinnati, OH) was presented by
Beyette [2] that demonstrated the ability to quantify both bilirubin and hemoglobin in the presence
of CSF. While accurate to within 25% in the concentration ranges of 0.1-0.15 g/dL hemoglobin
and 0.5-1.4 mg/dL bilirubin, the analysis approach is sensitive to the presence of other species
not incorporated into the model. Further, developing the algorithm model using more than two
species would greatly increase the number of measurements needed to accurately capture the
dynamics of the entire sample set.
This work demonstrates an improved spectral analysis approach for the quantification of bilirubin
and hemoglobin in real CSF samples using the preexisting Bilibox device platform. With these
methods, including cubic spline fitting to reduce signal spikes, derivative nonlinear curve-fitting,
and model adjustment due to binding estimates, bilirubin quantification is improved to an accuracy
of 15% relataive error and hemoglobin to within 10% for an identical sample set. The
quantification of two blood species, unconjugated bilirubin and methemoglobin, in addition to the
bilirubin and hemoglobin used previously was performed and shown to achieve a relative error of
20% of their assay-measured values using a relatively small sample set to develop the binding
corrections used in the model.
Support for this work was provided by F. R. Beyette, Jr. of the Electrical and Computer
Engineering Department and J. Clark of the Neurology Department at the University of Cincinnati
and POCCENT through NIH grant 1-U54-EB007954-01. Facilities were provided by the University
of Cincinnati.
References
[1] Zivin J. Hemorrhagic cerebrovascular disease. In: Goldman L, Ausiello D, eds. Cecil Medicine.
23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 432
[2] F. R. Beyette, Jr., et al., “Device for Quantification of Bilirubin in Cerebral Spinal Fluid,” IEEE
Transactions on Biomedical Engineering, 2010.
15

Point-of-Need Preparedness for Hematology, Hemostasis, and Transfusion
Crises Encountered in Critical Care, Emergencies, and Disasters
Corbin M. Curtis; William E. Dager, PhD; Rebecca J. Sonu, MD; Erika B. Ammirati, RAC,
MT(ASCP); Stephanie Sumner, BS; and Gerald J. Kost, MD, PhD, MS, FACB
Point-of-Care Testing Center for Teaching and Research (POCT•CTR),
UC Davis-LLNL Point-of-Care Technologies Center [NIBIB, NIH], and the
UCDHS Coagulation Service; School of Medicine, University of California, Davis; and
Ammirati Regulatory Consulting, Los Altos, CA
This paper strives to develop a multidisciplinary and multifaceted, yet integrated strategy of
technological development that addresses critical needs for the diagnosis, management, and
treatment of acute and chronic disorders requiring evidence-based point-of-care (POC) diagnostic
testing to support the specialties of hematology, hemostasis, and transfusion medicine. Tables
provide an overview of state-of-the-art POC tests and approaches, including a POC Technologies
Center-funded exploratory project device for blood donor screening (HIV-1/2, hepatitis B/C) that is
being reduced to commercial practice. Illustrated case studies demonstrate the need for
understanding the principles underlying therapeutic turnaround time, the POC coordinator,
instrument operation, quality control, operator competency, environmental durability, and
portability in victim- and patient-side settings. These principles are applicable not just to the
devices themselves, but also to knowledge packets necessary for the interpretation of results
obtained with different device formats that may employ, for example, dissimilar reference intervals
for the interpretation of test results. The recommended strategic plan places selected methods,
such as POC determination of hematocrit/hemoglobin, in the hands of first responders, who may
be pressed to make critical triage decisions, while other mobile approaches, such as coagulation
tests (PT, apt, ACT) needed for the support of surgery, are positioned in alternate care facilities
and in community hospitals. Impact is increased by planning POC testing in the context of costeffective
small-world networks that not only integrate urgent services on a routine daily basis, but
also enable regional health care delivery systems to better prepare for, and respond to
emergencies and disasters, including in low-resource countries.
16

Creation and Validation of an iPhone 4 Application for
Photographic Burn Wound Monitoring
Dillier A a , Jackson KN a , Nanduri H a , Yakoobinsky D a , Tran NK b , and Passerini AG a
a Department of Biomedical Engineering, University of California, Davis, CA
b Point-of-Care Testing Center for Teaching and Research and the University of California
Davis-Lawrence Livermore National Laboratory Point-of-Care Technology Center,
University of California, Davis
Background: Approximately 500,000 burn injuries require medical treatment each year. Serial
photography monitors and records wound healing; however, there are many challenges with
existing methods that decrease the reliability of serial photography for clinical observations. The
goal of this project was to create a novel smartphone application for the iPhone 4 that improves
serial photography of burn wounds by decreasing angle, coloring, and focusing inconsistencies.
Methods: The application was developed using Apple’s iOS software development kit (Cupertino,
CA) for use on their iPhone 4 platform. Angle consistency is achieved by overlaying a translucent
image of the last photograph taken with the image in the camera view finder, permitting imagematching
using patient skin markers or existing anatomical landmarks. Lighting and color
consistency is accomplished through the use of the camera’s flash with an additional diffuser.
Photograph focus is improved by adding a patient information input section, eliminating the need
for camera autofocus on the patient’s identification card.
Results: Proof of concept will be established by evaluating the application on simulated wounds.
Ten adult burn patients admitted to UC Davis Regional Burn Center (Sacramento, CA) will then be
recruited for clinical validation of the application. Two patients will be serially photographed (daily)
using both the iPhone 4 and the existing Kodak C913 camera (control). Following normal wound
photography protocols, hospital staff will photograph remaining participants using either the
iPhone 4 or the control. Photographs from both sources will be analyzed for color and angle
regularity via photo editing software and displayed using time-lapse techniques. Questionnaires
will be given to the clinical staff to evaluate the application’s ease of use.
Conclusion: The iPhone 4 application is expected to perform better than the control in 3 areas:
coloring, angle, and focusing. Survey results are expected to show similar ease of use for both
devices.
17

Environmentally Robust Non-invasive Wireless Vitals Monitor
for Disaster Care Settings
Enkhbayar, Enkh-Uchral; Ho, Vincent K.; Wu, Jenny W.; Yuen, David J.;
Tran, Nam K.; Passerini, Anthony G.
Department of Biomedical Engineering, University of California, Davis
Background. Recent natural
disasters called attention to the lack
of point-of-care technologies
available in the field. Currently,
disaster responders must use
multiple wired point-of-care devices
for vitals monitoring. Moreover,
these devices are susceptible to
environmental
extremes
encountered by disaster responders.
Objective. Develop an environmentally-robust, noninvasive, portable, wireless device that can
measure a patient’s heart rate, temperature, oxygen saturation, and blood pressure and
automatically store vitals data as an electronic format for review.
Methods. Literature searches and consultations with experts were performed to define ideal
device specifications. Specifications were ranked based on patient comfort, form factor, skin
coverage, accuracy, and ease of use. Each of these criterion was given a weighted score by
multiplying a raw score from 1-10 with a weighting factor. The sum of the weighted scores for
each criterion gave each device variant a total score. The devices with the highest total scores
were included in the prototype development plan. Prototype devices will be evaluated on a healthy
adult volunteer. After validation, prototypes will be stress tested for 60 minutes under “hot” (A1,
B3) and “basic” (B1, A2, A3, C1) conditions defined by United States MIL-STD 810G.1
Performance results post-stress testing will be compared to room temperature testing to confirm
environmental robustness under the defined test conditions.
Results. A design rendering of the prototype device is
shown in Figure 1. Prototype device specifications are
summarized in Table 1. Blood pressure and
temperature measurements are to be made using
sphygmomanometry and a thermistor, respectively.
Heart rate and oxygen saturation will be determined
using a pulse oximetry-based finger biosensor.
Common, commerciallyavailable AA batteries will be
used and wireless communications is to be facilitated
by Bluetooth®.
Conclusion. The wireless vitals monitor enhances
emergency and disaster responder capabilities by
eliminating cumbersome wires, being environmentally
robust, and automatically monitoring data for patient
care.
18

Dynamic thermal and humidity stresses on the performance of two point-ofcare
glucose reagent test strips for emergency and disaster care
William J. Ferguson, BS 1 ; Richard F. Louie, PhD 1 ; Stephanie L. Sumner, BS 1 ; Jimmy N. Yu 1 ;
Corbin M. Curtis 1 ; Kyaw Tha Paw U, PhD 2 ; and Gerald J. Kost, MD, PhD, MS, FACB 1 .
1 Point-of-Care Testing Center for Teaching and Research (POCT•CTR) and the UC Davis-
LLNL Point-of-Care Technologies Center [NIBIB, NIH], School of Medicine;
2 Land, Air, and Water Resources;
University of California, Davis
Objective: Point-of-care testing (POCT) reagents and devices can be operated in a variety of
environments, including the site of emergencies or disasters. Our objective is to characterize the
performance of reagent test strip from two glucose meter systems (GMS) in a dynamic stressed
environment.
Methods: Reagents strips from two commercial GMS (GMS1 and GMS2) were dynamically
stressed in an environmental chamber (Tenney T2RC) modeling temperature and humidity during
Hurricane Katrina. Glucose test strips were stressed for duration ranging from 8 to 680 hours.
Measurements obtained from stressed strips were compared to results from room temperature
control strips using three quality control (QC) test levels for GMS1 and two for GMS2.
Results: The duration of stress affected strip performance with GMS1 QC level 1 (P

Point-of-care pathogen detection for critical care and low resource settings
using multiplex linear-after-the-exponential polymerase chain reaction
Gentile NL 1 , Williams GV 2 , Czajka JW 2 , Reis AH 4 , Barry PA 1 , Polage CR 1 , Kost GJ 1 .
1 University of California, Davis, Davis, CA; 2 Smiths Detection Diagnostics, Edgewood, MD;
3 Smiths Detection Diagnostics, Watford, UK; and 4 Brandeis University, Waltham, MA.
Introduction. Globally, there is a need for development of point-of-care (POC) nucleic acid recognition
(NAR)-based pathogen detection devices capable of allowing diagnosis and treatment in low resource
settings. However, industry lacks NAR technologies to provide multiplex pathogen detection capabilities
at the POC. We will bridge the current gap in POC technologies by validating the diagnostic
performance of the Clinical Bio-Seeq TM System (Smiths Detection Diagnostics, Edgewood, MD), a
“sample in—answer out” platform that utilizes the Bio-Seeq TM 2 instrumentation, an automated Sample
Preparation Unit, and the Linear-After-The-Exponential polymerase chain reaction (LATE-PCR)
chemistry. The Clinical Bio-Seeq TM System is designed to provide the capability for a user to perform
multiplexed PCR in a POC setting without any molecular biology training.
Objective. The long-term goal is to facilitate the translation of the Clinical Bio-Seeq TM System from its
current advanced prototype status into the clinic, providing a platform that enables POC LATE-PCR
testing for a broad range of clinical settings with a diverse menu of infectious disease assays available
for use. We will validate LATE-PCR for the detection of septicemia and the Clinical Bio-Seeq TM
System’s feasibility as a POC device to provide rapid diagnosis in critically ill patients to facilitate early,
evidence-based treatment decisions. We target eight pathogens (Staphylococcus aureus, including
methicillin resistant strains, coagulase negative Staphylococcus, Pseudomonas aeruginosa,
Enterococcus species, Acinetobacter baumannii, Klebsiella species, Enterobacter species, and
Candida species) commonly found in critically ill patients.
Methods. Experiments consist of two components: a) bench (analytical) validation and b) clinical
evaluation. We will use genomic DNA and whole organisms from American Type Culture Collection
(ATCC) (Manassas, VA) as well as clinical isolates collected from the University of California, Davis
Medical Center (UCDMC) clinical microbiology laboratory for bench validation. Bench validation
involves five individual experiments that determine the assay’s LoD, dynamic range, analytical
specificity, multiplexing capabilities, and potential white blood cell (WBC) genomic DNA interference.
We use 1 mL aliquots of whole blood obtained from healthy asymptomatic volunteers spiked with
known concentrations of target pathogens. Clinical validation involves testing whole blood and swab
samples from 60 adult critically ill patients at UCDMC. Results are compared to blood culture. Arbitrated
case review determines the clinical significance of LATE-PCR results versus cultures. The study is IRB
approved.
Results. Experiments are in progress. We expect that LATE-PCR will compete with, or prove better
than other PCR assays when detecting eight target organisms. LoD in whole blood will be equivalent or
better than those of current PCR assays. Analytical specificity will be sufficient to prevent cross
reactivity. LATE-PCR will not exhibit interference when challenged with very high or very low genomic
DNA from white blood cells.
Conclusion. LATE-PCR using the Clinical Bio-Seeq TM System demonstrates the potential for rapid
point-of-care diagnosis of bacteremia in critically ill patients and represents a valuable NAR technique
that serves as an adjunct to blood culture in diagnosing bloodstream infections. Fast bedside
information will aid in early evidence-based treatment decisions of high value in critical care medicine.
20

Ischiban: Stroke Assessment Headband
Pooja Kadambi, Joe Lovelace, Scott Robinson, and Alex Androski
University of Cincinnati, Department of Biomedical Engineering, Medical Device Innovation
and Entrepreneurship Program: Undergraduate Senior Capstone
Stroke, a leading cause of death in the United States from 2005-2009, kills someone every
three minutes. Further, it is a leading cause of disability with over $73.7 billion spent on treatment
in 2010. For Ischemic Strokes which make up 87% of all strokes, clot-busting drugs such as
tPA, offer tremendous promise of improving survival and recovery rates when administered within
the “golden hour”. Unfortunately, these drugs are lethal to patients suffering from hemorrhagic
strokes. While CAT scan imaging technologies can differentiate the type of stroke, more than 70
percent of patients cannot be diagnosed inside of the “golden hour” because they are unable to
reach a hospital imaging center in time. Thus, a portable device that would allow EMTs to
differentiate stroke types will dramatically reduce time to treatment.
Figure 1 shows the device described in this paper which consists of an elastic headband
with EEG/EIS electrodes placed around the headband circumference. The device has a custom
electrode holder designed to enable fast (less than 2 min) deployment on the patient, provide low
electrode-skin contact impedance and dissipate the point-of-contact pressure on the patients
head. Conductive/abrasive gel is applied to the skin through a pre-loaded twist-top plunger
system ensuring controlled, quick, easy delivery. Additionally, the device provides efficient
management of wires that can be connected to either an EEG or EIS analysis platform. Finally, a
LED display is built into the wire management system to provide immediate user feedback that
indicates when electrodes are not making appropriate electrical contact.
In the paper we will present user feedback results from paramedics and firefighters who
were taught to attach the device to test subjects (Figure 2). Additionally, we will present
functionality testing verifying device operation in EEG mode using animal, cadaver and live human
testing (Figure 3).
21

Clot Detection in Brain Phantom Using a Real-Time, Non-Invasive,
Point-of-Care Electromagnetic Sensor
Madhuvanthi Kandadai 1 , Joseph Korpfhagen 2 , Joseph Clark 2 , George Shaw 1 , Opeolu A.
Adeoye 1
1 Department of Emergency Medicine, 231 Albert Sabin Way, Suite 1551
2
Department of Neuroscience, CARE/Crawley Building Suite E-870
University of Cincinnati
Goals: The main goal of this project was to detect (and distinguish between) clots and blood in an
in vitro model of an Intra Cerebral Hemorrhage. Electromagnetic (EM) radiation in the
radiofrequency (RF) range is transmitted across a brain phantom containing coagulating blood,
and changes in the received signal power are measured. Our hypothesis is that the received
signal power will be different between blood and clots due to differences in their structural and
dielectric properties. Based on the proof of concept results presented here, a sensor is being
developed for non-invasive and real-time detection of blood coagulation in the brain.
Materials and Methods: Citrated blood purchased from a blood bank is coagulated using a
solution of Calcium Chloride. Agar brain phantoms are prepared with a conductivity matching
brain conductivity at 37°C. The experiments are conducted at 37C. Antennae placed diametrically
across the phantom are used to transmit and receive EM radiation at 400MHz, generated using a
signal generator. The received signal power is measured using a spectrum analyzer.
Results and Discussion: An increase in the received signal power was observed as a function of
time of coagulation starting from the time at which coagulant was added to blood, with and without
the brain phantom gel. Figure 1 clearly illustrates the dependence of the nature of received signal
power on the extent of blood coagulation. Complete coagulation of the sample was confirmed by
manually examination of the sample.
Conclusions: The main conclusion of this study is that it is possible to distinguish between clots
and blood using the EM sensor. The long-term application of this device is in non-invasive
detection and real time monitoring of bleeding/coagulation in internal organs. Further refinement
of the technique is required to find the optimum frequencies for maximal difference in signal output
between clots and blood.
22

Point-of-Need Hemoglobin A1 c for Evidence-Based
Diabetes Care in Rural Small-World Networks
Anan Kanoksilp, MD; 1 Gerald J. Kost, MD, PhD, MS, FACB; 2,3 Daniel M. Mecozzi, BS; 3
Rebecca Sonu, MD; 3 Corbin Curtis; 3 and Jimmy N. Yu, BS 3
1 Khumuang Community Hospital, Buriram, Thailand.
2
College of Populations Studies, Chulalongkorn University, Bangkok, and
3Point-of-Care Testing Center for Teaching and Research (POCT&CTR) and the UC Davis-
LLNL Point-of-Care Technologies Center (NIBIB, NIH), School of Medicine, University of
California, Davis, California;
Objectives: The objectives of the study were (a) to perform pointof-care (POC) hemoglobin A1c
(HbA1c) testing at primary care units (PCUs) in rural villages, (b) to devise strategies for improved
diabetes control, (c) to improve efficiency managing high-volume diabetic patients, and (d ) to
implement a small-world network (SWN) of PCUs, a community hospital, and a regional hospital.
Methods: Hemoglobin A1c instruments were rotated through 11 PCUs on diabetes clinic days in
the Khumuang Community Hospital SWN, Buriram Province, Isaan, Thailand, then results
characterized statistically for demographic differences. Quality control checked instrument
consistency and operator competency.
Results: Point-of-care HbA1c brought evidence-based primary care to villages for the first time.
Only 17% had HbA1c of less than 6.5%. Non-normal distributions were right skewed. Mean (SD),
median (range), and third quartile HbA1c levels (%) were 8.3 (2.1), 7.8 (4Y17.5), and 9.3,
respectively, for all patients (N = 1188, aged 18Y92 years); 8.4 (2.3), 7.8 (4.9Y17.5), and 9.5 for
313 males; and 8.2 (2.0), 7.8 (4.1Y16.1), and 9.2 for 875 females. Median male/female HbA1c did
not differ significantly. Weighted-average top quartile HbA1c ranks at PCUs facilitated efficient
treatment of patients with poorly controlled diabetes.
Conclusions: Rapid on-site HbA1c testing of up to 150 diabetic PCU patients per day, quickly
and efficiently identified those who were poorly controlled. Unexpectedly, elevated HbA1c
changed primary care strategy, pulling together a rotating team of physicians, nurses, and a
pharmacist who adjust therapy and accelerate checks for albuminuria to prevent advancing
disease, dialysis, and adverse outcomes. This SWN motivates public health leadership to invest in
POC HbA1c monitoring and enables diagnostic screening.
This abstract reflects work published in:
Kost GJ, Kanoksilp A, Mecozzi DM, Sonu R, Yu JN, Curtis C. Point-of-need HbA1c for Evidence-
Based Diabetes Care in Rural Small-World Networks: Kumuang Community Hospital: Buriram,
Thailand. Point of Care: The Journal of Near-Patient Testing & Technology 2011;10:28-33.
23

Point-of-Care Testing and Continuous O 2 saturation Monitoring following the
Tsunami in the small-world network of Phang Nga Province, Coastal Thailand
Pratheep Katip, MT; b Gerald J. Kost, MD, PhD, MS, FACB a,c ; Audhaiwan Suwanyangyuen,
MBA; b Shayanisawa Kulrattanamaneeporn, PhD; d Nicole Gentile, BS; c and Jimmy Yu, BS c
a Affiliate Faculty, b College of Population Studies, Chulalongkorn University;
c
UC Davis-LLNL Point-of-Care Technologies Center and the POCT•CTR,
Pathology and Laboratory Medicine, School of Medicine, UC Davis; and
d Faculty of Social Sciences, Srinakharin Wirot University, Bangkok, Thailand
Objective. In 2004, an earthquake and Tsunami devastated Southeast Asia. We report on
adaptations in point-of-care testing (POCT) and continuous monitoring in Phang Nga, one of the
hardest hit coastal provinces in southern Thailand.
Methods. Early 2005, we studied four provinces, then in 2007-11, focused on Phang Nga by
field/phone/mail/email/fax survey of seven primary care units (PCUs), all seven community
hospitals (CHs), and both regional hospitals (RHs). We used short- and long-form Thai surveys,
photodocumented instruments, and assessed other resources.
Results. CH laboratories installed electrolyte analyzers. Pulse oximeters increased dramatically,
mainly through gifts of assorted formats. Nurses reported uncertainty with quality control and
calibration. Glucose meters remained common POC devices. CH microbiology is deficient.
Dengue hemorrhagic fever outbreaks require hourly bedside spun hematocrits for transfusion
decisions. Ambulance shortages and long travel times render transportation vulnerable.
Helicopters are unavailable in the small-world network, which we quantitate.
Conclusions. Education in quality control and POCT needs improvement. Pulse oximeters to
monitor oxygenation status during ambulance transfer, ED evaluation, and ventilation, are not
matched adequately by blood gas analyzer availability, nor by timely arterial pO 2 , pCO 2 , and pH
measurements. Noninvasive hemoglobin monitoring of Dengue patients would facilitate frequent
blood transfusions. However, overall preparedness improved.
This abstract reflects work published in:
Kost GJ, Tran NK. Continuous noninvasive hemoglobin monitoring: the standard of care and
future impact. Critical Care Medicine, 2011 [In Press]
24

A microdevice with integrated aptasensors for
detecting cell-secreted cytokines
Ying Liu, Jun Yan, Timothy Kwa, Michael Howland, Alexander Revzin
Department of Biomedical Engineering
University of California, Davis
We report the development of a miniature and quantitative interferon-gamma release assay for
in situ detection of the cytokine interferon gamma (IFN-γ). Using target-specific DNA aptamers
modified with a methylene blue redox reporter, the aptamer undergoes a conformational change
upon binding to IFN-γ, increasing the distance between the redox reporter and the electrode
surface and resulting in a change in the electrochemical signal. The sensor and cell capture
functions are integrated within a microfluidic device consisting of a functionalized glass substrate
with gold microelectrodes in contact with a molded polydimethylsiloxane (PDMS) flow channel.
Antibody (Ab) molecules are patterned at the bottom of micropatterned poly(ethylene glycol)
(PEG) hydrogel microwells, which define sites for cell attachment. The aptamer is assembled on
the electrode surface using gold-thiol chemistry. Red blood cell-depleted human blood is
introduced into the microfluidic device and then washed at pre-defined shear stress to remove
nonspecifically bound cells. This results in the isolation of pure CD4 positive cells on the Ab spots.
We then monitor IFN-γ secretion in response to mitogenic stimulation in real-time via square wave
voltammetry. The minimum levels of IFN-γ detectable with this approach are achieved after 15
minutes of activation time, requiring only 50 to 100 CD4 cells and therefore small blood volumes.
This technology could be used to produce a lab-on-a-chip diagnostic platform for monitoring
immune cell function from a fingerprick of whole blood without intensive sample preprocessing.
Quantifying IFN-γ release has great potential for diagnosing tuberculosis.
25

Integrated iPhone Spirometry and Breath
Metabolite Device for Asthma Monitoring
Alice M. Kwan 1 , Nicholas J. Kenyon 2 , Kenneth I. Joy 3 ,
1
Jean-Pierre Delplanque , Cristina E. Davis 1
1 Department of Mechanical and Aerospace Engineering
2 Division of Pulmonary and Critical Care Medicine
3 Division of Computer Science
University of California, Davis
I. Goals
Asthma is a disease that inflames and narrow the airways, making it difficult to breath. It
affects more than 22 million people in the United States. Although there is no known cure for
asthma, doctors alleviate most, but not all, asthma symptoms with medication – provided that the
symptoms are properly monitored by doctor and patient. Comprehensive, easy-to-use, and
portable asthma monitoring devices are therefore needed to allow doctors to routinely supervise
the patient and take the proper medical steps to improve their health.
We propose to accomplish this by developing a device that provides two unique functions
simultaneously. First, the device will couple a novel miniature spirometer to a personal mobile
device for real-time lung function monitoring that will be directly performed by the patient in their
day-to-day life. Secondly, we will integrate miniature chemical sensors into the device to monitor
exhaled breath metabolites that are related to asthma disease processes and health status. The
data from this instrument can be collected and conveyed to their clinician via telemetry/email
communications.
II. Methods
We aim to improve patient adherence to their prescribed asthma drug regimens by creating
an accurate, portable, and multifunctional sensor device that integrates with common personal
mobile devices such as smart phones or tablet devices. We will incorporate: (1) a miniature
spirometer to measure lung function parameters; (2) between 2-5 chemical sensors that uniquely
identify asthma-related exhaled biomarkers; and (3) programmed controls to efficiently acquire
data. Our proposed chemical sensors would be sensitive to carbon monoxide, nitric oxide,
methane, hydrogen, and carbon dioxide in exhaled breath.
III. Results
A simple prototype device that monitors asthma by measuring the maximum air flow while
a patient is exhaling has been completed, putting the project one step closer toward our end goal.
Our second generation device will incorporate chemical sensors to analyze asthma breath
metabolites, utilize an intuitive user interface, and streamline the data sharing process so that
patients can receive critical medical attention quickly and prevent the onset of serious asthma
attacks.
IV. Conclusion
Combining the diagnostic capabilities of several biomarkers ensures that the device fully
describes a patient’s asthma condition. Coupling chemical sensor technology with personal
mobile devices promotes frequent monitoring in a way that has not yet been achieved.
26

Demonstrating the Feasibility of Modeling Austere Climatic Profiles for
Simulation of Point-of-Care Testing in Disasters
Marine Lhote, BS 1 ; Mathieu Pirart, BS 1 ; William J. Ferguson, BS 2 ;
Richard F. Louie, PhD
2 ; and Gerald J. Kost, MD, PhD, MS, FACB 2
1
Faculty of Medicine, University Henri Poincaré Nancy 1, France
2 UC Davis – LLNL POC Technologies Center, Pathology and Laboratory, Medicine
Objective. The goal is to assess the readiness of point-of-care testing (POCT) reagents for use in
emergencies and disasters. Profiles modeling climate conditions of disaster sites are needed to test
POC reagent stability in these austere environments. The objective is to determine that temperature
and humidity profiles of past disasters can be accurately reproduced with an environmental testing
chamber.
Method. Five profiles modeling temperature and humidity conditions experienced during disasters
in New Orleans (Louisiana, USA), Port-au-Prince (Haiti), Banda Aceh (Indonesia), Springfield
(Massachusetts, USA) and Sendai (Japan) were created with data from the National Climatic Data
Center. Each profile was programmed onto the Tenney BTRC Environmental Chamber to run three
24-hour cycles. An Omega OM62 data logger recorded internal chamber temperature and humidity
every five minutes. At each hour, mean internal chamber temperature and humidity from the three
cycles were compared to profile set points. To illustrate the ability of the chamber to reproduce each
profile, mean temperature and humidity were plotted along with hourly set points.
Results. The figure shows the mean internal chamber temperature and humidity for a 24-hour
period compared to defined set points for two of the five profiles: Hurricane Katrina (Frame A) and
earthquake Haiti (Frame B). Overall mean
temperature difference between internal
chamber conditions and chamber set
points was 0.1°C ± 0.28°C for Frame A and
0.1°C ± 0.17°C for Frame B. For humidity,
the mean difference was 2.0% ± 2.40% for
Frame A and 2.0% ± 1.84% for
Frame B.
Maximum absolute difference of internal
temperature did not exceed 0.71°C for both
profiles; relative humidity deviated slightly
during the ramp down segment of the
profile, with differences from set points no
greater than 6.4%.
Conclusions. Tenney BTRC
Environmental Chamber can accurately
model temperature and humidity profiles
and is an appropriate instrument to
simulate varying conditions for medical
device robustness studies.
Figure: 24-hour internal temperature and humidity
profile modeling the conditions of hurricane Katrina,
New Orleans, Louisiana, 2006 (Frame A), and the
2010 earthquake in Haiti (Frame B).
27

Rapid Molecular Detection of Influenza A and H275Y Mutation
Conferring Resistance to Oseltamivir
Patrick Long BS, Kathy Mangold PhD, Karen Kaul MD PhD
Department of Pathology
NorthShore University HealthSystem
Evanston, IL 60201
Background:
Rapid molecular detection of influenza has become the standard for diagnosis and appropriate
use of antiviral agents. However, variation in the viral genome and the rapid emergence of
oseltamivir-resistant seasonal H1N1 in the United States in 2009 indicates the additional need for
influenza A subtyping, and direct detection of the causative nucleotide substitution. We have
developed a rapid and robust detection system for influenza A and oseltamivir-resistant seasonal
and pandemic influenza A (H1N1) viruses using redundant primer cocktails to withstand viral
sequence drift that can be readily transferred to point-of-care instrumentation.
Methods:
In silico comparison of more than 9,200 influenza A gene sequences was performed to design
primers flanking a highly conserved region of the M2 gene, consisting of a single forward primer
and four overlapping reverse primers. TheH275Y mutation, conferring oseltamivir-resistance in
the N1 subtype, was detected via a cocktail of three redundant forward primers and a single
reverse primer. Viral RNA was prepared from nasopharyngeal swab samples using an EasyMag
nucleic acid extractor (Biomerieux, France). The one-step RT-PCR assays were optimized using
the Roche LightCycler 2.0 (Indianapolis, IN), with amplicon detection via SybR green
fluorescence.
Results:
The M2 influenza A primers detected available subtypes of influenza A (H3N2, seasonal H1N1,
2009 pandemic H1N1) from the years 2003-2010, including those with sequence variation. The
H275Y mutation primers detected 5 of 5 2009 seasonal H1N1 samples and 4 of 4 2009 pandemic
H1N1 samples tested.
Conclusion:
This pair of RT-PCR assays successfully detected all influenza A and oseltamivir-resistant
(H275Y) viruses. The multi-primer strategy will avoid false negative test results due to the evolving
and highly variable genome of influenza. Optimization and validation of this approach on the
POC platform to rapidly allow clinicians to determine optimum therapy without delays associated
with centralized testing.
28

In vivo demonstration of an implantable bladder pressure sensor
in an ambulatory canine subject
Steve J. A. Majerus 1,2 , Paul C. Fletter 2 , Paul Zaszczurynski 2 ,
4,
Hui Zhu
5 , Margot S. Damaser 2,3 , Steven L. Garverick 1,6
1 Dept. of Electrical Engineering and Computer Science, Case Western Reserve University
2 Advanced Platform Technology Center, Louis Stokes Cleveland VA Medical Center
3 Dept. of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic
4 Division of Urology, Louis Stokes Cleveland VA Medical Center
5 Dept. of Urology, University Hospitals, Case Medical Center
6 West Wireless Health Institute, La Jolla, California
Background and Objectives.
Diagnosis of urological disorders
can be imprecise because
symptomatic leakage—often caused
by motion—is difficult to replicate in
a catheterized patient. A chronic bladder pressure sensor would
enhance diagnosis and confirm efficacy of treatment by recording
bladder activity as the patient behaves normally. The wireless intracavity micro-manometer (WIMM) is being
developed to provide bladder pressure recording in chronic applications (Fig. 1). A wired WIMM prototype
was implanted within the bladder of an ambulatory canine
subject to capture motion artifacts and bladder contractions.
Methods. The wired prototype (Fig. 2) was packaged for acute
implantation in an ambulatory canine subject; wires carried
power and data to and from the WIMM. The encapsulation
used silicone-silicone bonding to the silicone tube that
contained stainless steel wires, and a silicone/nylon membrane
over the pressure cavity (Fig. 3 and Fig. 4), to avoid moisture
ingress. The WIMM and a reference device, similarly packaged
but containing just a pressure transducer, were implanted submucosally
and the wires were tunneled to an exit site near the shoulders. Ambulatory
pressure signals were recorded from the WIMM and reference device, at
3.5 and 20 kilosamples/s respectively, for 5 days after a 5-day healing
period.
Results. The unfiltered recordings revealed high-frequency noise, which
may have been due to implantation complications
and motion artifacts. The signals were filtered to 10
Hz and recordings of bladder events were captured
with correlation coefficient ≥ 0.8 when compared to
the submucosal reference (Fig. 3 and 6). Signals
recorded while the subject was anesthetized
demonstrated better correlation (≥ 0.9) to pressures
recorded via an intravesical micro-tip catheter.
Conclusions. The WIMM can suitably capture
submucosal pressure recordings in an ambulatory
subject, although complications arising from the wired device limit the
recording accuracy. Future versions will be wireless and implanted in
larger animals to test more advanced system features.
29

A point-of-care proviral PCR test for HIV-1 detection in infants
Sujit Jangam 1 , Sally McFall 2* , Robin L Wagner 2 , Douglas Yamada 4 ,
Abhishek K Agarwal
2 , Kunal Sur 3 and David Kelso 2
1
Life Technologies, Foster City, CA
2
Center for Innovation in Global Health Technologies,
Department of Biomedical Engineering, Northwestern University
3
Quidel Molecular, San Diego, CA
4 Department of Microbiology, Immunology, and Molecular Genetics, University of
California, Los Angeles
Background: We prototyped an integrated, quantitative PCR (qPCR) system that detects HIV-1
provirus for use at the point-of-care (POC). The system utilizes a novel DNA extraction method
(FINA – filtration isolation of nucleic acids), a disposable PCR card with on-board reagent storage,
and a portable, battery back-up analyzer.
Methods: Blood is collected and lysed in a detergent coated capillary, releasing genomic DNA.
This lysate is added to a DNA trapping membrane and a capillary force driven wash removes
inhibitors. Next, the DNA membrane is inserted into the PCR card that contains lyophilized
reagents and buffer. The PCR card is inserted into the analyzer that performs PCR mix assembly,
thermal cycling and fluorescence detection, and displays the test results. Standard curves were
plotted with HIV(-) blood spiked with HIV provirus to assess PCR efficiency and LOD. An
exogenous internal control assay targeting an amplicon in the pumpkin hydroxy pyruvate
reductase gene was multiplexed with the HIV assay. Sixty blinded clinical samples were tested
and compared to the Total Nucleic Acid Test COBAS® Ampliprep/COBAS® TaqMan® System to
determine sensitivity and specificity.
Results: Improvements to FINA extraction included decreasing the LOD to 5 HIV-1 copies/100 µL
blood, and multiplexing of an exogenous internal control. In a clinical evaluation, 97% sensitivity
and 100% specificity were achieved. The FINA extraction and HIV assay were utilized in the POC
HIV-1 qPCR system consisting of three disposables (blood separator module, sample introduction
module, and assay card) and a portable qPCR analyzer. qPCR tests detected HIV and internal
control targets from blood spiked with HIV proviral DNA at various concentrations and internal
control DNA.
Conclusions: We have demonstrated proof-of-concept of a POC platform. The results from this
study provide insights into the design constraints of consumables and instrumentation to be used
in the next generation of the POC test.
30

Advancement toward a POC Influenza Diagnostic Device:
Development of a Laboratory Based Nucleic Acid Extraction System
Utilizing Immiscible Phase Filter Purification
Sally McFall 1 , Jennifer McCauley 1 , Robin Wagner 1 , Zaheer Parpia 1 , Renana Ashkenazi 1 ,
Frank Bolton 1 , Abhishek Agarwal 1 , Mark Fisher 2 , Kunal Sur 3 , and David Kelso 1
1
Center for Innovation in Global Health Technologies,
Department of Biomedical Engineering, Northwestern University
2 Northwestern Global Health Foundation
3 Quidel Molecular, San Diego, CA
Background: The recent novel H1N1/Influenza A pandemic illustrates the need to swiftly
diagnose, treat and limit the spread of emerging viruses. Patient testing at the point-of-care (POC)
will improve clinical management and infection control. We are developing a POC influenza RTqPCR
screening device to meet this need. Toward this goal, an automated sample preparation
system has been developed for use in optimization of nucleic acid (NA) extraction.
Methods: We have developed a novel NA extraction method that eliminates meticulous washing
of conventional methods by magnetically transporting NAs bound to paramagnetic particles
(PMPs) though a hydrophobic liquid separating the aqueous lysis and elution solutions. An
automated system and disposable cartridge were developed to streamline sample preparation.
The system contains 3 work stations: a sonicator for mixing, a magnetic station to manipulate
PMPs and a heating station. The cartridge moves between work stations on a computer controlled
stage allowing the user to walk away during the extraction.
Results: The influenza RNA purification utilizes an immiscible phase filter where RNA is captured
on PMPs in aqueous lysis buffer, passed through a hydrophobic fluid to the elution buffer and deabsorbed
from the PMPs. The PMP movement instead of fluids eliminates pumps, pipette tips and
aspirators used in other automated processors. The Influenza assay was multiplexed with an
exogenous internal control for sample preparation recovery and amplification inhibition. These
assays will be used to determine optimal PMP size and NA binding chemistry for influenza RNA
isolation.
Conclusion: With the development of the automated extraction system, the required specimen
volume, optimal PMP size and nucleic acid binding chemistry for RNA isolation and purification for
influenza RT-qPCR assays can be determined. In the future, this extraction system will be
integrated into the diagnostic system and/or used as a stand-alone unit providing purified samples
for other applications.
31

Profession Specific Needs Assessment
Daniel Mecozzi, BS, and Keith Brock, BS
Point-of-Care Testing Center for Teaching and Research (POCT•CTR),
UC Davis-LLNL Point-of-Care Technologies Center [NIBIB, NIH]
School of Medicine, University of California, Davis
Background. The devastation and disruption to infrastructure and healthcare caused by disasters
is well documented. Point-of-care testing offers a mobile resource light option to fill the need for
diagnostic testing during disaster triage and treatment. Maximizing stakeholder input into
development of diagnostic devices is critical to ensure the greatest impact on disaster response.
Methods. The membership of the American Association of Clinical Chemists was surveyed.
Questions focused on device design and critical pathogen targets. Multiple choice questions were
analyzed with the Chi Square for Goodness of Fit test and ranking questions were analyzed with
Analysis of Variance and Tukey’s Multiple Comparison Test (SPSS 19, Chicago, IL).
Results. Results indicate that survey respondents prefer direct sample collection (P

Development of a Microwave-Accelerated Metal-Enhanced Fluorescence
(MAMEF) as a Point of Care Assay for the Detection of Neisseria gonorrhea
1
Johan H. Melendez 1 , Yongxia Zhang 1 , Charlotte Gaydos 2 and Chris D. Geddes 1*
Institute of Fluorescence and Department of Chemistry and Biochemistry,
University of Maryland Baltimore County
2 Div Infectious Disease, Medicine, Johns Hopkins University Medical School
Background: Neisseria gonorrhoea (NG) is the second most commonly reported notifiable
disease in the United States. Rapid and accurate identification of NG clinical isolates are critical
for the successful management and control of gonorrhea infections. While the use of nucleic acid
amplification tests (NAATs) is widely accepted and effective, there is still an urgent need for more
rapid and sensitive molecular methods which could be easily employed in the field as point-ofcare
tests.
Methods: A MAMEF assay targeting the Por gene of the NG genome has been designed, and
used for the rapid and sensitive detection of NG DNA. Rapid detection of NG DNA is mediated by
a two-step process involving the release of NG DNA from bacterial cells through a rapid, and lowcost
microwave-based approach followed by detection of DNA with an ultra sensitive and rapid
MAMEF assay. Sensitivity and specificity testing as well as validation with clinical samples are
ongoing.
Results: Using “bow-tie” structures to focus the microwaves into a lysing reaction, NG bacterial
cells were successfully lysed after a 9 second microwave-enhanced lysing reaction as
demonstrated by lack of bacterial growth on culture media and gram staining results. Following
rapid lysing, detection of NG DNA is mediated after a 20 second microwave-enhanced
fluorescence reaction. Overall, lysing and detection of NG DNA can be achieved in less than one
minute using this microwave-enhanced approach.
Conclusions: We have successfully detected NG DNA in less than one minute using an ultra
rapid lysing and detection method based on metal-enhanced fluorescence. The rapid nature of
this platform coupled with the superior sensitivity of metal-enhanced fluorescence approaches
provide the basis for the successful development and implementation of MAMEF as a point-of
care test for detection of gonorrhea infections.
33

Rapid p24 Antigen Test for Point-of-Care Diagnosis of Acute Pediatric HIV
Infection
2
Arman Nabatiyan PhD 1 , Zaheer A. Parpia PhD* 1 , Robert Elghanian PhD* 1 ,
Diana R. Hardie MD
2 , David M. Kelso PhD 1
*Contributed equally to this work
1
Center for Innovation in Global Health Technologies,
Department of Biomedical Engineering, Northwestern University
Virology laboratory of the National Health Laboratory Services (NHLS), Groote Schuur
Hospital,
and University of Cape Town, Cape Town, South Africa.
Currently, the majority of HIV infected infants are found within limited-resource settings where
inadequate screening for HIV, due to the lack of access to simple and affordable point-of-care
tests, impedes implementation of anti-retroviral therapy. Here we report development of a low-cost
dipstick p24 antigen lateral flow assay that can facilitate the diagnosis of HIV for infants in
resource-poor conditions. A heat shock methodology was developed to optimize disruption of
immune complexes present in the plasma of infected infants. A membrane-based filter device for
rapid and efficient collection of 25μL plasma from 80μL of heel-stick whole blood was also
developed for use with our heat shock p24 assay. The analytical sensitivity of the assay using
recombinant p24 antigen is 50pg/mL (2 pM) with whole virus detection as low as 42.5k RNA
copies/mL plasma. In a blinded study comprising 51 archived infant samples from the Women and
Infants Transmission Study, our assay demonstrated an overall sensitivity and specificity of 90%
and 100% respectively. In field evaluations of 389 fresh samples from South African infants, a
sensitivity of 95% and specificity of 99% was achieved. The assay is simple to perform, requires
minimal plasma volume (25μL) and yields a result in less than 40 minutes making it ideal for
implementation in resource-limited settings. At present we are in the process of pilot
manufacturing 10,000 assay test strips and plasma separator devices and 80 beta-units of the
heat shock instrument for field evaluation of target pediatric specimens at six sites across Africa
within the coming year.
34

Increasing Leukemia Treatment Compliance through Social Networking
Meric Ozturk, Steven Pham, Phillip Shaecher, James Tan
Department of Biomedical Engineering, University of California, Davis
Introduction: Treatment compliance, a term used to describe the ability and dedication of a
patient to stick to a prescribed routine as prescribed by their doctor, in young leukemia patients is
particularly low. However, recent research strongly suggests that an immersive medical
environment can positively affect patient behavior. Our goal is to tie together social media and the
emerging mHealth paradigm to increase treatment compliance in these traditionally non-compliant
patients. The objective is to develop data transport architecture capable of extracting data from a
POCT device and securely piping it over a smartphone to a social media platform, which will
integrate this data with an EMR database.
Materials and Methods: The design calls for an entire system consisting of an adapter, a mobile
phone application, and a web platform. For the POCT1-A adapter we chose a Bluetooth-enabled
prototype based on the Arduino platform. For the intermediary link we chose to create a
smartphone application for the Android operating system that had everything built into the
application itself and could send and receive data from the website database. We chose to
develop the web platform internally due to concerns with privacy and flexibility. This platform will
incorporate data syncing, multiple views and users, and other necessary database and social
network features. The website will be written in Ruby and the database will be based on SQLite.
Results and Discussion:
Results will be obtained in a future test when our system is implemented in the leukemia
treatment center at the UC Davis Medical Center. This will allow us to quantitatively determine if
compliance increases in patients using our system.
Conclusions:
We believe that our tests will show that compliance will be increased when our system is
implemented in young leukemia patients’ treatment regimens.
35

Impact of dynamic environmental stress testing on glucose
quality control solution for disaster preparedness
Stephanie L. Sumner, BS 1 ; Richard F. Louie, PhD 1 ; William J. Ferguson, BS 1 ; Jimmy N. Yu 1 ;
Corbin M. Curtis 1 ; Kyaw Tha Paw U, PhD 2 ; and Gerald J. Kost, MD, PhD, MS, FACB 1 .
1 Point-of-Care Testing Center for Teaching and Research (POCT•CTR) and the UC Davis-
LLNL Point-of-Care Technologies Center [NIBIB, NIH], School of Medicine;
2 Land, Air, and Water Resources;
University of California, Davis
Goal: To characterize the effects of dynamic thermal and humidity stress on glucose quality
control solution.
Background: Point-of-care (POC) reagents like glucose quality control (QC) solutions are
important in deciding glucose monitoring system (GMS) performance for acceptability for use with
patients. Austere environments that may be present during disaster and emergency situations can
exceed the suggested QC temperature and humidity ranges. Health care personnel should be
aware of the effects of temperature and humidity on glucose QC solution.
Methods: QC solutions from two GMS (GMS1 and GMS2) were evaluated; three levels for
GMS1 and two levels for GMS 2. Vials of each level of QC for each GMS were dynamically
stressed for more than four weeks in an environmental chamber programmed to simulate the
temperature and humidity encountered during Hurricane Katrina. All measurements were
completed with test strips stored at room temperature. Stressed QC was tested at temperatures of
45°C and 23°C. Stressed QC was paired with control QC that was stored at room temperature.
Results: The difference between stress and control was consistently greater for QC at 45°C than
23°C for GMS 2. QC Level 1 for GMS 2 had an average absolute mean paired difference (SD) for
QC stressed at 23°C of 0.47 mg/dL (1.62) and 8.0 mg/dL(1.94) at 45°C. The average absolute
mean paired difference for QC Level 2 of GMS 2 for QC stressed at 23°C was 1.96 mg/dL(6.85)
and 24.39mg/dL(7.04) at 45°C. For GMS 1, average absolute mean paired differences for QC
stressed at 45°C and 23°C were all less 3 mg/dL for all QC levels.
Conclusion: Dynamic environmental stress affected the performance of POC glucose QC
solution for GMS 2. Appropriate storage of reagents can help prevent the improper use of GMS.
36

The Benefits of Use of Point-of-Care HIV Tests in Disaster Care
Chloe S. Tang; Richard F. Louis, PhD
Point-of-Care Testing Center for Teaching and Research (POCT•CTR)
UC Davis-LLNL Point-of-Care Technologies Center [NIBIB, NIH],
School of Medicine, University of California, Davis
Objective: The devastating impacts of disasters such as Hurricane Katrina and the earthquake in
Haiti have further opened the door for evaluations on point-of-care (POC) HIV testing. The
objective is to compare non-POC to POC HIV tests and extract the benefits of POC testing in
disaster settings.
Methods: Literature review through online sources such as the Centers for Disease Control and
PUBMED were used.
Results: Six FDA-approved POC HIV tests currently exist, many of them CLIA waived or
classified under moderate complexity. In clinical studies of OraQuick, the use of oral fluid has a
sensitivity of 99.3% and specificity of 99.8%. Whole blood specimens have a sensitivity and
specificity of 99.6% and 100%. Plasma specimens are extremely accurate at 99.6% and 99.9%.
Results from a POC HIV test take less than an hour to receive.
Conclusions: The sensitivity and specificity of the POC HIV tests are comparable to those of
non-POC, gold standard HIV tests such as the enzyme immunoassay and western blot. These
easy-to-use tests negate the need for highly trained laboratory technicians, complex equipment,
and electricity – all things that may be inaccessible after a disaster. Turnaround time for results is
much shorter for POC tests. This reduces the loss of follow-up and need for repeated visits. HIVpositive
patients can receive anti-retroviral treatment sooner – increasing its effectiveness. The
option to use less-invasive oral fluid specimens has been well received, and may increase
willingness to be tested. POC tests can also be beneficial for health care personnel who may have
a greater chance of being exposed to HIV while working outside the proper protection of a normal
hospital setting. POC HIV tests can be effective for providing better care in disaster settings.
Health care personnel should be educated on POV HIV tests in preparation for future disasters.
37

Point-of-care Mobile Technology for Early Detection of Diabetes Mellitus
Wilson J. To, Anthony Cheung
Department of Pathology and Laboratory Medicine
University of California, Davis Medical Center
This study introduces innovative application technologies into mobile healthcare by pairing a
widelyavailable smartphone platform with computer-assisted intravital microscopy (CAIM) to
provide costeffective point-of-care analysis of the in vivo microcirculation to detect diabetic
microangiopathy in children in developing countries. In diabetes mellitus, symptoms or
pathologies present themselves only after significant vasculopathic damages have occurred.
Since it has been previously shown that changes in the microcirculation are reflective of early
changes that manifest in a disease, it would be during this small time window that the greatest
potential exists for ameliorating and managing the deleterious effects of the disease.
CAIM is an objective and quantitative real-time technology designed to non-invasively capture in
vivo video images of the conjunctival microcirculation. The design concept uses state-of-the-art
image processing algorithms for visual detection of active adjustments in blood vessel tone
(morphometry – diameter and tortuosity) and subsequent changes in flow dynamics (velocity). A
simple user interface allows clinicians to easily navigate the application to calculate vessel
tortuosity and diameter, and simultaneously determine blood flow velocity on a mobile device. By
providing a robust platform to view, analyze and detect vasculopathy on a device that spans
across various socioeconomic boundaries, healthcare can be provided to low-resource
environments in order to improve the overall welfare of the community.
This study uses a mixed platform of social entrepreneurship to generate short- and long-term
funding for development and distribution. The alignment in the objectives of the project with
nonprofit organizations, foundations, and venture firms will enable the technology to be funded
through the aims of promoting and funding efforts of tackling socioeconomic and medical issues.
By later incorporating revenue-generating practices, the project will be able to create a
sustainable business model that will reflect today's business world's progressive global
responsibilities. This project was partially funded by the Gates Foundation.
38

Mapping Point-of-Care Performance Using
Locally-Smoothed Median and Maximum Absolute Difference Curves
Nam K. Tran, PhD, MS, FACB, and Gerald J. Kost, MD, PhD, MS, FACB
Point-of-Care Testing Center for Teaching and Research (POCT•CTR)
UC Davis-LLNL Point-of-Care Technologies Center [NIBIB, NIH]
School of Medicine, University of California, Davis
Background. The goal is to introduce visual performance mapping convenient and efficient for
establishing acceptance criteria and facilitating decisions regarding the utility of hospital point-ofcare
devices. This non-parametric technique is unique in that it reveals the quality of performance
locally, as opposed to globally.
Methods. After presenting theoretical foundations, we illustrate the approach by applying it to six
hospital glucose meter systems (GMSs) using clinical observations from multicenter (n=2,767)
and multisystem (n=613, n=100) evaluations. An Appendix illustrates how to draw locallysmoothed
(LS) median absolute difference (MAD) and maximum absolute difference (MaxAD)
curves.
Results. LS MAD curves identified breakouts from the error tolerance limit. LS MaxAD
breakthroughs showed locations of extreme errors. One multi-sensor interference- and
hematocrirt-correcting GMS displayed a flat LS MAD curve until it reached a glucose breakout of
179 mg/dL (9.94 mmol/L) and generated breakthroughs that could affect bedside decision making,
but less erratically than other systems, for which performance is inadequate for hospital critical
care. In particular, we discovered Class I (meter high, reference low) and Class II (converse)
discrepant values. Class I errors could lead to inappropriate insulin dosing and hypoglycemic
episodes in tight glucose control.
Conclusions. LS MAD-MaxAD curves help assess the performance of point-of-care testing.
Visual mapping of systematic and random errors locally over the entire analyte measurement
range in a single integrated display is an advantage when considering the adverse impact of
zones of poor quantitative performance on specific clinical applications, threshold-driven bedside
decisions, and the care of critically ill patients.
This abstract reflects work published in:
Kost GJ, Tran NK. Mapping Point-of-Care Performance Using Locally-Smoothed Median and
Maximum Absolute Difference Curves. Clinical Chemistry and Laboratory Medicine, 2011 [In
press].
39

A New Point of Care System to Measure Plasma Bilirubin Concentration
Richard P Wennberg, MD 1-2 , Pablo Giraudi, PhD 2 , Carlos Coda-Zabetta, PhD 2 ,
Chiara Greco
2 , Cristina Bellarosa, PhD 2 , and Claudio Tiribelli, MD 2
1 University of Washington, Seattle, WA
2 Italian Liver Foundation, Trieste, Italy
Disclosure: RW and CT share part ownership of pending patent, but did not participate in
clinical evaluation
Background and Objectives. Hyperbilirubinemia
continues to be a common cause of kernicterus in many
developing nations and a major concern
in Western countries. Existing point of
care (POC) instruments to screen
babies' total plasma bilirubin levels (TB)
are costly and not readily available in
resource poor countries. Our objective
is to develop a simple inexpensive
screening system to measure total
serum bilirubin.
Methods. We have developed a POC
system that requires 20 mL blood
applied to a blood-plasma separator
that delivers 2-3 mL plasma to a
contiguous nitrocellulose membrane.
The intensity of yellow is measured
using a hand held battery operated
reflectometer containing a blue LED to measure bilirubin
and a second LED to detect hemoglobin contamination.
Results. A. Plasma enriched with increasing bilirubin
produced a reproducible logarithmic decrease in
reflectance, providing an algorithm for measuring serum
bilirubin.
B. There was a good correlation between total bilirubin
measured with Bilistick and direct spectrophotometry using
reconstituted adult blood (hematocrit 40-55) with bilirubin
concentrations ranging up to 30 mg/dL.
C. We compared Bilistick and clinical laboratory results
using blood obtained by heel stick from jaundiced
newborns. Hematocrits ranged 55-75%. Three patients
with Bilistick results higher than clinical laboratory values
Reflectance (U.A.)
3000
2500
2000
1500
1000
Bilirubin by Bilistick (mg/dL)
500
0
20
15
10
5
0
y = -851ln(x) + 3109
R² = 0.999
0 10 20 30 40
UCB by UB analyzer (mg/dL)
y = 1.098x + 0.954
R² = 0.763
0 5 10 15 20
Bilirubin by Lab (mg/dL)
had evidence of mild hemolysis (green reflectance); a correction algorithm was not applied.
Conclusions. We have developed an inexpensive battery operated point of care system to screen
newborns for hyperbilirubinemia. It is easy to operate, requires a tiny drop of blood, and produces
a result in 30-90 seconds with reasonable accuracy up to about 30 mg/dL total bilirubin. We hope
the system will assist the global effort to eradicate kernicterus in developing countries.
A
B
C
40

Theory, Principles, and Practice of Optimizing Point-of-Care
Small-World Networks for Emergency and Disaster Care
Jimmy N. Yu, BS; Gerald J. Kost, MD, PhD, MS, FACB; Nam K. Tran, PhD, MS, FACB
Point-of-Care Testing Center for Teaching and Research (POCT•CTR) and the UC Davis-
LLNL Point-of-Care Technologies Center [NIBIB, NIH]
School of Medicine, University of California, Davis
Small-world networks for healthcare delivery evolve naturally but are constrained by geographic
topologies and discrete interruptible transportation routes. New diagnostic and monitoring
technologies, placed strategically at hubs and nodes, can improve workflow and accessibility of critical
information for decision making. Here, practice principles for optimizing point-of-care testing (POCT) in
small-world networks are applied to enhance planning for emergency care and disaster preparedness.
We discovered that the tangible small-world network must be transformed into a virtual time domain
network in order to anticipate the dynamics of successful responses. Once that is done, it becomes
apparent why POCT, such as handheld cardiac biomarker testing, is valuable—during emergencies
and disasters, it optimizes therapeutic turnaround time (TTAT), the time from test ordering to
treatment, and on a daily basis in the ICU and ER,
improves efficiency for physicians, nurses, and
patients alike. In low-resource settings, not the cost
but the net integrated value of POCT in the SWN
must be determined. In other settings,
demographically sound POC preparedness can pay
off in terms of potential lives saved, especially in
regions of heterogeneous population clusters
versus healthcare facilities.
Fig. 1. Small-world network for Kalasin Province in rural
Isaan, Thailand.
In Kalasin the mean (SD, median, range) distance from
Community Hospitals to the Regional Hospital is 56 (29, 53,
13-109) km. Transport time by ambulance is 60 (30, 60, 15-
120) minutes, much too long for patients with acute myocardial
infarction.
Fig. 2. Transformation of the SWN from the physical to temporal domain.
Community Hospitals in the red zone should perform cardiac troponin I or T on site to obviate overnight observation, speed
ambulance transport, and also improve safety with pulse oximetry monitoring en route. POC cardiac biomarker testing at Tha
Khan Tho Community Hospital (upper left) could allow patient transport directly west to the Khon Kaen Heart Center by
bypassing the provincial capitol and intermediate nodes, while reducing TTAT for catheterization and coronary stent (not
available within the province). Community Hospitals lack microbiology facilities. Thus, POC pathogen detection by nucleic acid
testing would be useful in all zones, since results will target antimicrobials administered immediately.
41

Connecting Point-of-Care Informatics in Emergencies and Disasters
Jimmy N. Yu, BS; T. Keith Brock, BS; Daniel M. Mecozzi, BS;
Nam K. Tran, PhD, MS, FACB; and Gerald J. Kost, MD, PhD, MS, FACB
Point-of-Care Testing Center for Teaching and Research (POCT•CTR)
UC Davis-LLNL Point-of-Care Technologies Center [NIBIB, NIH]
School of Medicine, University of California, Davis
Objective. The goal of this paper is to identify strategies for connectivity that will optimize point-ofcare
testing (POCT) organized as small-world networks in disaster settings.
Methods. We evaluated connectivity failures during the 2010 Haiti Earthquake, applied smallworld
network concepts, and reviewed literature for point-of-care (POC) connectivity systems.
Results. Medical teams responding to the Haiti Earthquake faced connectivity failures that
affected patient outcomes. Deploying robust wireless connectivity systems – such as those
utilizing WiMax, WiFi, and Bluetooth technologies – can enhance the efficiency of the disaster
response by improving healthcare delivery, medical documentation, logistics, response
coordination, communication, and telemedicine. Virtual POC connectivity education and training
programs can enhance readiness of disaster responders.
Conclusions. The admirable humanitarian efforts of over 4,000 organizations substantially
impacted the lives of earthquake victims in Haiti. However, the lack of connectivity and smallworld
network strategies, combined with communication failures, during early stages of the relief
effort must be addressed for future disaster preparedness.
Figure 1. Field Area Network for Victim
Information Connectivity
The diagnostic lab-in-a-backpack 1 (A, B)
equips first responders with the tools
necessary to perform diagnoses in field
settings. Field area networks (FANs) use
Bluetooth to connect point-of-care devices to
handheld computer nodes (e.g., iPhone,
satellite phone, and smartphone). FANs can
be modular (e.g., FAN1, 2, 3, and 4) allowing
addition and multiplexing of POC tests, such
as pathogen detection, pulse oximetry,
electrocardiograms, and blood pressure
monitors, to fit the diagnostic needs of the
disaster response. Bridged by two-way
satellite, FANs provide long- and short-range
communication and data management for
victim identification, position, history,
treatment, and triage (C) that spans
geographic barriers or disaster-produced
obstacles.
This abstract reflects work published in:
Yu JN, Brock TK, Mecozzi DM, Tran NK, Kost GJ. Future Connectivity for Point of Care in
Emergency and Disaster. Point of Care: The Journal of Near-Patient Testing & Technology. 2010;
9:185-192. (Accessible for free at PubMed Central: PMC3086779)
42

MAP: COURTYARD MARRIOTT TO EDUCATION BUILDING
Directions
After exiting the Courtyard Marriott main entrance, turn right onto Y Street then left onto 45 th
Street. The Education Building is immediately visible on your right. Enter the north structure
opposite the Blaisdell Library. Room 1222 is located on the first floor.
43

MAP: UC DAVIS HEALTH SYSTEM VISITOR PARKING LOTS
Red circles identify visitor parking lots 4 and 14.
**Purchase a parking permit at the yellow kiosks
found in the parking lot.
**Attendees staying at the Courtyard Marriott do
not need to pay for a parking permit if parking on
Marriott premises
44

MAP: SACRAMENTO INTERNATIONAL AIRPORT TO HOTEL
Directions
Get onto I-5 South. Drive for 9.6 miles. Exit onto CA-99 South/US-50 East towards Fresno.
Continue on US-50 East for 3.2 miles. Take the 34 th Street Exit and turn left onto 34 th Street.
Take the first right onto T Street. Make a slight right turn onto Stockton Blvd. Turn left onto Y
Street, the hotel will be on your right.
Version 12, June 16, 2011
45