Biomedical Engineering – From Theory to Applications

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292 Biomedical Engineering – From Theory to Applications with the limitted functionalities of conventional pipettes. The use of ion beams for surface finishes can possibly alivieate some of the tedious work often involved in finishing capilaries. Ion beam polishing could also contribute to the characterization of roughness and finishes in a quantitative manner. In fact, ion beam milling is a useful tool to reverse engineer the morphology of pipettes altogether by sequential polishing and further image reconstruction (Ostadi et al., 2009). These tomographic capabilities could prove useful in quality control assessment of current and upcomming cellular tools. Kometani et al. have provided a wealth of examples in highly customized micromanipulators, pending application in relevant cellular and subcellular scenarios. Future experiments should aim at inseminating mouse oocytes with FIB-polished glass pipettes, as initial tests by Campo et al. merely addressed piercing feasibility, i.e. mechanical sturdiness, sharpness, and early indication of biocompatibility. However, the real application scenario has not yet been demonstrated since no injection tests have been performed to show functionality. Similarly, FIB-sharpened microfluidic-pipettes are pending injection testing. In addition, microfulidicpipettes manufacturing is ameanable to exploring materials other than silicon oxide, that could be of interest to complementary applications such as electrophysiology. Similarly to glass pipettes, microfluidic pipettes could be fitted with additional components, either by bottomup or top-down microtechnologies. Resulting structures from the addition of sensors and actuators with different functionalities need to be tested in adequate scnearios and further assess biocompatibility. We have discussed in detail how FIB with the assistance of gallium ions and carbon deposition, has gone well beyond proof of concept in terms of innovative design and micromanufacturing. Future directions in the microtechnology applications to the life sciences are likely to build upon FIB capabilities and also explore upcomming ion-bem microscopies. Looking forward, building upon FIB capabilities could be explored in the materials space, as well as in the functionality space of ion beam-produced tools. On the materials front, most FIB manufacturing for cellular tools has exploited the structural robustness of DLC. However, a number of chemistries are available in commercial FIB, with increasingly purified sources (Botman et al., 2009). Deposition of gold (Au), paladium (Pd), and platinum (Pt) could be specially interesting for devices requiring electrical conduction, such as those used in electrophysiology. Tipically, higher purity nanostructures are deposited by ion beam than by electron beam-assited deposition (Utke, 2008). However, further work will need to assess the effects of source purity on chemistry and mechanical characteristics of ion beam-deposited structures. Amongst emergent novel micromachining and micromanufacturing technologies ameanable to contributing to cellular tools, Helium Ion Microscopy (HIM) is possibly the most relevant. Seminal papers describe this novel microscopy that serves both as a characterization (Scipioni et al., 2009) and a manufacturing tool (Postek et al., 2007, Maas et al., 2010) in micro-nano systems. With the use of hellium (He) ions and, smilarly to FIB, highly customizable milling capabilities, HIM could have a possitive impact on the pending biocompatibility assessment. Adequate biocompatibility studies are needed to assess ion dose implantation on tools and devices and the effects at the subcellular and cellular levels, as well as in vivo. These will be critical parameters that could hinder the implementation of ion-beam technologies in the life sciences. In all likelihood, these strategies will need to be developed by multidisciplinary teams. In fact, assembly of highly multidisciplinary teams, encompassing bio-medical scientists and microsytem technologists, are surely needed to fully explore the possibilities of impactful task–specific tools in the context of subcellular manipulation.
Micro-Nano Technologies for Cell Manipulation and Subcellular Monitoring It is also crucial to develop a mechanistic understanding of how design, manufacturing, and piercing techniques affect cellular structures. Indeed, the impact of pipette parameters on handling is unclear, as mechanisms responsible for different failure modes during conventional piezo-assisted piercing only recently have been subject of investigation (Ediz et al., 2005). Mechanistic studies would establish a much-needed correlation between the (quantifiable) physical parameters of pipettes and piercing techniques with cellular response in the context of elasticity theory and biology. In terms of operator training and quantification of the exerted force, the advent of haptics in the context of robotics could provide quantification of cell injection force and also to improve success statistics in piercing and other operational procedures. There is already enough evidence suggesting that the combination of haptic and visual feedback improves handling (Pillaresetti et al., 2007). Further development of these technologies will, most likely, make them available to the bio-medical community at large. Novel piercing technologies have also appeared in the recent literature, such as Ross-Drill, promoting a rotational approach to cell piercing, rather than tangential (tipical of piezo-assited drilling) and claiming decreased training effort for operators. The possibility of combining Ross- Drill with FIB-polished pipettes has already been sugested (Campo et al., 2010a). SPECIALTY APPLICATION CITATION CELL INJECTION ROTATIONAL OSCILLATION-DRILL MICROMANUFACTURING OF ERGENC, EDIZ & OLGAC CELL INJECTION CUSTOMIZED TIPS IN GLASS CAPILARIES AND MICROFLUIDIC PLATFORMS CAMPO & PLAZA CELL INJECTION 3-D STUDY OF GLASS PIPETTE GEOMETRY BY MICROMACHINING TECHNIQUES USE OF CARBON NANOTUBES FOR OSTADI & OLGAC CELL MICROINJECTION ELECTROPHYISIOLOGY AND NANOFLUIDIC INJECTION SCHRLAU&BAU CELLULAR/ SUBCELLULAR HANDLING MICROMANUFACTURING OF CUSTOMIZED MANIPULATORS IN GLASS CAPILARIES MICROMANUFACTURIG OF CUSTOMIZED KOMETANI& MATSUI SUBCELLULAR MONITORING SENSORS AND ACTUATORS IN GLASS CAPILARIES KOMETANI& MATSUI SUBCELLULAR DRUG DELIVERY POLYMERIC MICELLE CARRIERS GENG & DISCHER SUBCELLULAR DRUG DELIVERY BACTERIA-MEDIATED DRUG DELIVERY AKIN&BASHIR SUBCELLULAR DNA DELIVERY POLYMER MICROSPHERES WALTER & MERKLE SUBCELLULAR MONITORING AND DELIVERY* PROOF OF CONCEPT: BIOCOM-PATIBLE INSERTION OF MICROCHIPS ON CELLS FERNANDEZ-ROSAS, GOMEZ-MARTINEZ & PLAZA PROOF OF CONCEPT: LCE PHOTO- CAMACHO-LOPEZ, SMART MATERIALS** PROPELLED IN AN AQUOUS PALFFY-MUHORAY & ENVIRONMENT SHELLEY MECHANICAL ACTUATORS* PROOF OF CONCEPT: BIMORPH THERMAL NANO- ACTUATORS BY FIB CHANG & LIN HAPTIC TECHNOLOGY IN CELLULAR HANDLING HAPTIC FEED-BACK IN COMBINATION WIH VISUAL INSPECTION DURING CELL PIERCING PILLARISETTI & DESAI *This is a promising approach in subcellular monitoring and delivery. * *This approach has not been applied to cellular or subcellular environments. Table 3. List of highlighted technologies according to specialty, detailing specific application and citation included in the references in Section 6. 293
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BIOMEDICAL ENGINEERING - FROM THEOR
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free online editions of InTech Book
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VI Contents Chapter 9 Targeted Magn
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X Preface stand-alone and readers c
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6 Biomedical search engine Scientif
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12 Bireme http://regional.bv salud.
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14 Semantic Networks analysis Biome
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120 6. Conclusion Biomedical Engine
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150 5. Conclusions Biomedical Engin
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162 1 st phase : half year 4 2 nd p
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166 7. Innovative active training B
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172 12. Maturing projects’ story
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180 16. Acknowledgments Biomedical
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190 R* M M M M MR*M O O O O M O R*
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196 Fig. 9. Chemical structure of 5
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198 Relative Intensity (AU) Biomedi
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204 2. Preparation of IO nanopartic
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Biomedical Engineering – From Theory to Applications

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