Bio-MEMS - Knowledge

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Weirs are shallow mesa-like sections used to restrict flow to narrow slots between layers without posts. One advantage of using weirs is that the absence of posts allows more effective recycling of retentate for flow across the filter to wash off clogged cells. Magnetic beads are used to aid in analyte separation. These microscopic beads are functionalized with target molecules and moved through microfluidic channels using a varying magnetic field. This serves as a quick method of harvesting targets for analysis. After this process is complete, a strong, stationary magnetic field is applied to immobilize the target-bound beads and wash away unbound beads. The H-filter is a microfluidic device with two inlets and two outlets that takes advantage of

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been found to change the Young's modulus of the cantilever. Changing cantilever stiffness will also change its resonant frequency, and thus the noise in the oscillation signal must be analyzed to determine whether the resonant frequency is also a function of changing elasticity. One common use for this technique is in detecting nucleotide mismatches in DNA because the variation in mass caused by the presence of an incorrect base is enough to change the resonant frequency of the cantilever and register a signal. Mass sensing is not as effective in fluids because the minimum detectable mass is much higher in

133: 737: 150: 835: 1008:. Screw valves, unlike Quake and ice valves, maintain their level of flow restriction without power input, and are thus ideal for situations where the valve position may remain mostly constant and actuation by a human operator is acceptable. Electromagnetic solenoid valves have similar actuation times compared to Quake valves, but have larger footprints and are not integrated into the device substrate. This is an issue when device dimensions are an issue, such as in implantable devices. 968:. The basic scheme involves two perpendicular flow conduits separated by an impermeable elastomeric membrane at their intersection. Controlled air flow passes through one conduit while the process fluid passes through the other. A pressure gradient between the two conduits, which is tuned by changing the control air flow rate, causes the membrane to deform and obstruct flow in the process channel. In MSL, the channels for both the process fluid and the control fluid are cast out of an 1336: 992:(TE) units are used to transport heat away from the plug. Because of the limited temperature difference that TE units can provide, multiple are often chained in series to produce subzero temperatures at the substrate-fluid interface, allowing for more rapid cooling. Current state of the art ice valve technology features short closing times (0.37 s at 10 μL/min) and also operates at high flow rates (1150 μL/min). Ice valves were first introduced in 1995 where pressurized liquid 2543: 2466: 1463:

analysis. Red dots mean that the corresponding gene was expressed at a higher level in the treated sample. Conversely, green dots mean that the corresponding gene was expressed at a higher level in the untreated sample. Yellow dots, as a result of the overlap between red and green dots, mean that the corresponding gene was expressed at relatively the same level in both samples, whereas dark spots indicate no or negligible expression in either sample.

1447: 2077:, and bone tissues. Conventional methods of studying oxygen effects relied on setting the entire incubator at a particular oxygen concentration, which limited analysis to pair-wise comparisons between normoxic and hypoxic conditions instead of the desired concentration-dependent characterization. Developed solutions include the use of continuous axial oxygen gradients and arrays of microfluidic cell culture chambers separated by thin 1026: 1853:, large fluid volumes (~0.1 – 2 mL per sample), and tedious human labour. The requirement of human labour also limits the number and length between time points for experiments. Microfluidic cell cultures are potentially a vast improvement because they can be automated, as well as yield lower overall cost, higher throughput, and more quantitative descriptions of single-cell behaviour variability. By including 952: 981: 2268: 17: 1861:. However, this type of continuous microfluidic cell culture operation presents its own unique challenges as well. Flow control is important when seeding cells into microchannels because flow needs to be stopped after the initial injection of cell suspension for cells to attach or become trapped in microwells, dielectrophoretic traps, micromagnetic traps, or 1693:

saliva, blood, or urine samples and in an integrated approach perform sample preconditioning, sample fractionation, signal amplification, analyte detection, data analysis, and result display. In particular, blood is a very common biological sample because it cycles through the body every few minutes and its contents can indicate many aspects of health.

2246:, but controlling local density is difficult and it is often difficult to decouple effects between soluble signals in the medium and physical cell–cell interactions. Micropatterning of cell adhesion proteins can be used in defining the spatial positions of different cells on a substrate to study human ESC proliferation. Seeding stem cells into 1561: 1630:, are optically transparent, not inhibitory, and can be used to coat an electrophoretic glass channel. Various other surface treatments also exist, including polyethylene glycol, bovine serum albumin, and silicon dioxide. There are stationary (chamber-based), dynamic (continuous flow-based), and microdroplet ( 1777:

Funding is scarce for tropical disease research. In addition, there are many regulatory hurdles that must be cleared before a medical device is approved, which can cost tens of millions of dollars. Thus, companies focusing on tropical diseases must often combine their research objectives for tropical

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for rapid heating and cooling, but can poison the polymerase reaction. Silicon substrates are also opaque, prohibiting optical detection for qPCR, and electrically conductive, preventing electrophoretic transport through the channels. Meanwhile, glass is an ideal material for electrophoresis but also

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distances. The advantages of PCR chips include shorter thermal-cycling time, more uniform temperature which enhances yield, and portability for point-of-care applications. Two challenges in microfluidic PCR chips are PCR inhibition and contamination due to the large surface-to-volume ratio increasing

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microarrays are often used for large-scale screening and expression studies. In cDNA microarrays, mRNA from cells are collected and converted into cDNA by reverse transcription. Subsequently, cDNA molecules (each corresponding to one gene) are immobilized as ~100 μm diameter spots on a membrane,

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as measured electrically or optically. When a biochemical reaction takes place and is captured on the cantilever, the mass of the cantilever changes, as does the resonant frequency. Analysis of this data can be slightly less straightforward, however, as adsorption of sample to the cantilever has also

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is the motion of uncharged particles due to induced polarization from nonuniform electric fields. Dielectrophoresis can be used in bio-MEMS for dielectrophoresis traps, concentrating specific particles at specific points on surfaces, and diverting particles from one flow stream to another for dynamic

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and diffusion to separate components that diffuse across the interface between two inlet streams. By controlling the flow rate, diffusion distance, and residence time of the fluid in the filter, cells are excluded from the filtrate by virtue of their slower diffusion rate. The H-filter does not clog

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through three different temperatures. Heating up and cooling down in conventional PCR devices are time-consuming and typical PCR reactions can take hours to complete. Other drawbacks of conventional PCR is the high consumption of expensive reagents, preference for amplifying short fragments, and the

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to isolate various types of CTCs based on their specificities (Fan et al., 2013). Other notable advancements include the creation of nano-Velcro surfaces by Hsian-Rong Tseng's team at UCLA, designed to enhance cell capture efficiency through nanostructured polymer fiber meshes (Tseng et al., 2012),

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Protein microarrays have stringent production, storage, and experimental conditions due to the low stability and necessity of considering the native folding on the immobilized proteins. Peptides, on the other hand, are more chemically resistant and can retain partial aspects of protein function. As

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Most diagnostic devices on the market can only test for one disease. Moreover, most devices are binary output (yes/no) without nuanced information on the patient's condition. Thus, in addition to developing tests for more diseases, scientists are currently working to expand the complexity of these

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with reduced tissue damage, reduced pain, and no bleeding. Microneedles can also be integrated with microfluidics for automated drug loading or multiplexing. From the user standpoint, microneedles can be incorporated into a patch format for self-administration, and do not constitute a sharp waste

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It is difficult to manufacture MEMS diagnostic devices outside of the laboratory setting. Much of the research on these devices takes place in climate controlled laboratories, where the devices can be tested shortly after they are produced. However, as many of these devices are used to screen for

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and their sequences. There are many different types of biological entities used in microarrays, but in general the microarray consists of an ordered collection of microspots each containing a single defined molecular species that interacts with the analyte for simultaneous testing of thousands of

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is the dependency of the rate of wicking on environmental conditions such as temperature and relative humidity. Paper-based analytical devices are particularly attractive for point-of-care diagnostics in developing countries for both the low material cost and emphasis on colorimetric assays which

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must be separated. Sieves, weirs, inertial confinement, and flow diversion devices are some approaches used in preparing blood plasma for cell-free analysis. Sieves can be microfabricated with high-aspect-ratio columns or posts, but are only suitable for low loading to avoid clogging with cells.

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The ability to perform medical diagnosis at the bedside or at the point-of-care is important in health care, especially in developing countries where access to centralized hospitals is limited and prohibitively expensive. To this end, point-of-care diagnostic bio-MEMS have been developed to take

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chip by metallic pins. For detection, fluorescently-labelled single strand cDNA from cells hybridize to the molecules on the microarray and a differential comparison between a treated sample (labelled red, for example) and an untreated sample (labelled in another color such as green) is used for

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Most of the new microfluidic devices rely on antibodies to capture or fluorescently label CTCs. But other options are available. Z. Hugh Fan, a professor at the University of Florida, uses ligand-binding nucleic acid sequences called aptamers, which he attaches to the channels in a microfluidic

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samples around on the cantilever, without submerging the cantilever, minimally impacting its oscillation. This technology is in its infancy, however, and it is still not able to be used beyond a few, limited applications. The advantage of using cantilever sensors is that there is no need for an

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through the use of parallel conduits of variable path length and or diameter. The net result of having a variety of parallel flow channels of varying length is that material initially at the edge of the laminar flow profile can be repeatedly redistributed to the opposite edge, thus drastically

2582:). Drug delivery by microneedles include coating the surface with therapeutic agents, loading drugs into porous or hollow microneedles, or fabricating the microneedles with drug and coating matrix for maximum drug loading. Microneedles for interstitial fluid extraction, blood extraction, and 2285:

test for stem cells and their size needs to be controlled to induce directed differentiation to specific lineages. High throughput formation of uniform sized embryoid bodies with microwells and microfluidics allows easy retrieval and more importantly, scale up for clinical contexts. Actively

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Kim, D.-H.; Lu, N.; Ma, R.; Kim, Y.-S.; Kim, R.-H.; Wang, S.; Wu, J.; Won, S. M.; Tao, H.; Islam, A.; Yu, K. J.; Kim, T.-i.; Chowdhury, R.; Ying, M.; Xu, L.; Li, M.; Chung, H.-J.; Keum, H.; McCormick, M.; Liu, P.; Zhang, Y.-W.; Omenetto, F. G.; Huang, Y.; Coleman, T.; Rogers, J. A. (2011).

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Venkat Chokkalingam, Jurjen Tel, Florian Wimmers, Xin Liu, Sergey Semenov, Julian Thiele, Carl G. Figdor, Wilhelm T.S. Huck, Probing cellular heterogeneity in cytokine-secreting immune cells using droplet-based microfluidics, Lab on a Chip, 13, 4740-4744, 2013, DOI: 10.1039/C3LC50945A,

65:) chips. In this definition, lab-on-a-chip devices do not strictly have biological applications, although most do or are amenable to be adapted for biological purposes. Similarly, micro total analysis systems may not have biological applications in mind, and are usually dedicated to 2254:

communications has also been studied using microfluidics whereby negative pressure generated by fluid flow in side channels flanking a central channel traps pairs of cells that are in direct contact or separated by a small gap. However, in general, the non-zero motility and short

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with a photolabile protecting group are exposed to the entire surface and the chemical coupling process only occurs where light was exposed in the previous step. This process can be repeated to synthesize oligonucleotides of relatively short lengths on the surface, nucleotide by

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which impinge on the piezocrystal, and extracellular voltage changes are backscattered ultrasonically by the piezocrystal, allowing for measurement. A network of so-called "neural dust" motes can map signals throughout a region of the body where the micro-sensors are implanted.

69:. A broad definition for bio-MEMS can be used to refer to the science and technology of operating at the microscale for biological and biomedical applications, which may or may not include any electronic or mechanical functions. The interdisciplinary nature of bio-MEMS combines 6174:

Hochberg, Leigh R.; Serruya, Mijail D.; Friehs, Gerhard M.; Mukand, Jon A.; Saleh, Maryam; Caplan, Abraham H.; Branner, Almut; Chen, David; Penn, Richard D.; Donoghue, John P. (2006). "Neuronal ensemble control of prosthetic devices by a human with tetraplegia".

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to improve deeper insertion and better electrode-tissue contact for transduction of high-fidelity sounds. Integrating microelectronics onto thin, flexible substrates has led to the development of a cardiac patch that adheres to the curvilinear surface of the

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flow. For continuous-flow separation, the general idea is to apply a field at an angle to the flow direction to deflect the sample flow path toward different channels. Examples of continuous-flow separation techniques include continuous-flow electrophoresis,

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One inexpensive method of producing valves with fast actuation times and variable flow restriction is multilayer soft lithography (MSL). Valves produced through this fabrication technique are called Quake valves, because they were first created in the lab of

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with microfluidic cell cultures may help in this regard, but have inherently lower throughput due to the microscope probe having only a small field of view. The Berkeley Lights Beacon platform has resolved the issue of collection and detection by performing

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Lithographic methods for microfluidic device manufacturing are ineffective in forming the screw-type mechanisms used in macroscale valves. Therefore, microfluidic devices require alternative flow control techniques, a number of which are currently popular:

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can improve existing functionality, add new capabilities for surgeons to develop new techniques and procedures, and improve surgical outcomes by lowering risk and providing real-time feedback during the operation. Micromachined surgical tools such as tiny

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formation and organization. Bio-MEMS have been used to research how to optimize the culture and growth conditions of stem cells by controlling these factors. Assaying stem cells and their differentiated progeny is done with microarrays for studying how

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Microfluidic technology is relatively economical due to batch fabrication and high-throughput (parallelization and redundancy). This allows the production of disposable or single-use chips for improved ease of use and reduced probability of biological

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transducers to liquid reservoirs can be used in these circumstances to generate narrow size distribution of aerosols for better drug delivery. Implantable drug delivery systems have also been developed to administer therapeutic agents that have poor

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microenvironment with patterned topographic and biochemical surfaces for controlled spatiotemporal cell adhesion, as well as minimization of dead volumes. Micropumps and microvalves can automate tedious fluid-dispensing procedures and various

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Ionescu, Mihail H.; Winton, Brad R.; Wexler, David; Siegele, Rainer N.; Deslantes, A.; Stelcer, Eduard; Atanacio, Armand J.; Cohen, David D. (2012). "Enhanced biocompatibility of PDMS (polydimethylsiloxane) polymer films by ion irradiation".

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of the device, and device explantation. Most drugs also need to be delivered in relatively large quantities (milliliters or even greater), which makes implantable bio-MEMS drug delivery challenging due to their limited drug-holding capacity.

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on metal or dielectric surfaces. The resonance changes when biomolecules are captured or adsorbed on the sensor surface and depends on the concentration of the analyte as well as its properties. Surface plasmon resonance has been used in

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Despite the fact that diffusion times are significantly shorter in microfluidic systems due to small length scales, there are still challenges to removing concentration gradients at the time scales required for microfluidic technologies.

682:-style samples such as body fluids and soil), as well as its natural filtering properties that exclude cell debris, dirt, and other impurities in samples. Paper-based replicas have demonstrated the same effectiveness in performing common 5898:

Torisawa, Yu-suke; Chueh, Bor-han; Huh, Dongeun; Ramamurthy, Poornapriya; Roth, Therese M.; Barald, Kate F.; Takayama, Shuichi (2007). "Efficient formation of uniform-sized embryoid bodies using a compartmentalized microchannel device".

1819:, which improves cell capture via geometrical modifications (Soper et al., 2011). These innovations collectively enhance the sensitivity and specificity of CTC detection, providing valuable tools for cancer prognosis and treatment. 1236:

between two electrodes are measured as a result of a biomolecular reaction. Conductive measurements are simple and easy to use because there is no need for a specific reference electrode, and have been used to detect biochemicals,

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Chung, Bong Geun; Flanagan, Lisa A.; Rhee, Seog Woo; Schwartz, Philip H.; Lee, Abraham P.; Monuki, Edwin S.; Jeon, Noo Li (2005). "Human neural stem cell growth and differentiation in a gradient-generating microfluidic device".

4259: 812:) perpendicular to the flow direction. Sorting and focusing of the species of interest is achieved because an electrophoretic force causes perpendicular migration until it flows along its respective isoelectric points. 2056:

Microfluidics can leverage its microscopic volume and laminar flow characteristics for spatiotemporal control of biochemical factors delivered to stem cells. Microfluidic gradient generators have been used to study

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Clark, Sherrie G.; Haubert, Kathyrn; Beebe, David J.; Ferguson, C. Edward; Wheeler, Matthew B. (2005). "Reduction of polyspermic penetration using biomimetic microfluidic technology during in vitro fertilization".

281:-based microfabrication and this revolutionized the bio-MEMS field. Since then, the field of bio-MEMS has exploded. Selected major technical achievements during bio-MEMS development of the 1990s include: 862:

Microfluidic features can be fabricated on the cellular scale or smaller, which enables investigation of (sub)cellular phenomena, seeding and sorting of single cells, and recapitulation of physiological

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in cell culture medium. Due to the need for cells to be fed periodically with fresh medium and passaged, even testing a few conditions requires a large number of cells and supplies, expensive and bulky

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Foudeh, Amir M.; Didar, Fohid Fatanat; Veres, Teodor; Tabrizian, Maryam (2012). "Microfluidic designs and techniques using lab-on-a-chip devices for pathogen detection for point-of-care diagnostics".

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Wanunu, Meni; Cao, Qingqing; Mahalanabis, Madhumita; Chang, Jessie; Carey, Brendan; Hsieh, Christopher; Stanley, Ahjegannie; Odell, Christine A.; Mitchell, Patricia; Feldman, James; Pollock, Nira R.;

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are also being developed. The efficiency of microneedle drug delivery remains a challenge because it is difficult to ascertain if the microneedles effectively penetrated the skin. Some drugs, such as

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and contamination by carrying out PCR in microdroplets or microchambers. PCR in droplets also prevents recombination of homologous gene fragments so synthesis of short chimeric products is eliminated.

1140:. Suspended microchannel resistors are a special type of cantilever design that are able to work around this limitation using microfluidic channels inside the cantilever. These channels can move 193:

in their seminal paper proposing the use of miniaturized total chemical analysis systems for chemical sensing. There have been three major motivating factors behind the concept of μTAS. Firstly,

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via silicon and metals in the electrodes. Michigan probes have been used in large-scale recordings and network analysis of neuronal assemblies, and the Utah electrode array has been used as a

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sensing and mass sensing, or micro- and nano-scale plates or membranes. In stress sensing, the biochemical reaction is performed selectively on one side of the cantilever to cause a change in

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Toriello, Nicholas M.; Liu, Chung N.; Mathies, Richard A. (2006). "Multichannel Reverse Transcription-Polymerase Chain Reaction Microdevice for Rapid Gene Expression and Biomarker Analysis".

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Cho, Brenda S.; Schuster, Timothy G.; Zhu, Xiaoyue; Chang, David; Smith, Gary D.; Takayama, Shuichi (2003). "Passively Driven Integrated Microfluidic System for Separation of Motile Sperm".

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Lu, Hang; Koo, Lily Y.; Wang, Wechung M.; Lauffenburger, Douglas A.; Griffith, Linda G.; Jensen, Klavs F. (2004). "Microfluidic Shear Devices for Quantitative Analysis of Cell Adhesion".

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allow medical professionals to easily interpret the results by eye. Compared to traditional microfluidic channels, paper microchannels are accessible for sample introduction (especially

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Lo, Ronalee; Li, Po-Ying; Saati, Saloomeh; Agrawal, Rajat; Humayun, Mark S.; Meng, Ellis (2008). "A refillable microfabricated drug delivery device for treatment of ocular diseases".

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Microfluidics refers to systems that manipulate small (μL, nL, pL, fL) amounts of fluids on microfabricated substrates. Microfluidic approaches to bio-MEMS confer several advantages:

1380:. They can be used for detection of mutations and expression monitoring, and gene discovery and mapping. The main methods for creating an oligonucleotide microarray are by gel pads ( 4183:

Martensis, TheodoreCosmo; Kusler, Brenda; Yaralioglu, Goksen (2005). "Microfluidic sonicator for real-time disruption of eukaryotic cells and bacterial spores for DNA analysis".

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and externally located ultrasonic transducers. Sonication is also used widely for cell lysis and homogenization in both macro and microfluidic systems. The primary mechanism of

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Lu, Yao; Shi, Weiwei; Qin, Jianhua; Lin, Bingcheng (2010). "Fabrication and Characterization of Paper-Based Microfluidics Prepared in Nitrocellulose Membrane By Wax Printing".

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such as left-right asymmetry during development. Macro-scale studies do not allow quantitative analysis of shear stress to differentiation because they are performed using

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tropical diseases, they must be robust enough to survive in hot, humid conditions. They must also be stored for long periods from the time of production to the time of use.

1874: 1727:. A lytic buffer stream can be introduced alongside a stream containing cells and by diffusion induces lysis prior to further analysis. Cell analysis is typically done by 6999: 5055:

Gómez-Sjöberg, Rafael; Leyrat, Anne A.; Pirone, Dana M.; Chen, Christopher S.; Quake, Stephen R. (2007). "Versatile, Fully Automated, Microfluidic Cell Culture System".

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is often employed to provide local mixing of streams through the generation of ultra-high energy acoustics. Microfluidic chips utilizing sonication mixing can have both

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to produce proteins of interest; whereas peptide microarrays use the SPOT technique (stepwise synthesis of peptides on cellulose) or photolithography to make peptides.

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Fung, Wai-To; Beyzavi, Ali; Abgrall, Patrick; Nguyen, Nam-Trung; Li, Hoi-Yeung (2009). "Microfluidic platform for controlling the differentiation of embryoid bodies".

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Arcand, B. Y.; Bhatti, P. T.; Butala, N. V.; Wang, J.; Friedrich, C. R.; Wise, K. D. (2004). "Active positioning device for a perimodiolar cochlear electrode array".

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Tamayo, Javier; Ramos, Daniel; Mertens, Johan; Calleja, Montserrat (2006). "Effect of the adsorbate stiffness on the resonance response of microcantilever sensors".

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Prefabricated mechanical screw valves and solenoid valves require no advanced microfabrication processes and are easy to implement in soft substrate materials like

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Functional protein arrays display folded and active proteins and are used for screening molecular interactions, studying protein pathways, identifying targets for

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for chemical detection, require less time for processes and reactions to complete, and produces less waste than conventional macrofluidic devices and experiments

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Albrecht, Dirk R.; Tsang, Valerie Liu; Sah, Robert L.; Bhatia, Sangeeta N. (2005). "Photo- and electropatterning of hydrogel-encapsulated living cell arrays".

1889:. A handheld microfluidic cell culture incubator capable of heating and pumping cell culture solutions has also been developed. Due to the volume reduction in 6287:

Viventi, J.; Kim, D.-H.; Moss, J. D.; Kim, Y.-S.; Blanco, J. A.; Annetta, N.; Hicks, A.; Xiao, J.; Huang, Y.; Callans, D. J.; Rogers, J. A.; Litt, B. (2010).

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have been reproduced through photolithography on paper to achieve a slimmer profile and lower material cost while maintaining compatibility with conventional

5855:(2005). "Microfluidic application-specific integrated device for monitoring direct cell-cell communication via gap junctions between individual cell pairs". 3699:

Martinez, Andres W.; Phillips, Scott T.; Whitesides, George M. (2010). "Diagnostics for the Developing World: Microfluidic Paper-based Analytical Devices".

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A passive flow mixing element. Laminar flow with axial concentration gradients flows in, and laminar flow with diminished concentration gradients flows out.

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Futai, Nobuyuki; Gu, Wei; Song, Jonathan W.; Takayama, Shuichi (2006). "Handheld recirculation system and customized media for microfluidic cell culture".

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and microvalves, where fluid metering is straightforward to determine as opposed to continuous flow systems by micromixers. A fully automated microfluidic

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samples with different antibodies to study the changes in expression of specific proteins and protein modifications during disease progression, as well as

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biosensors, measurements of electric potential at one electrode are made in reference to another electrode. Examples of potentiometric biosensors include

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Bhatia, S.N.; Balis, U.J.; Yarmush, M.L.; Toner, M. (1998). "Probing heterotypic cell interactions: Hepatocyte function in microfabricated co-cultures".

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cannot identify post-translational modification of proteins, which directly influences protein function. Thirdly, some bodily fluids such as urine lack

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Ice valves operate by transporting heat away from a single portion of a flow channel, causing the fluid to solidify and stop flow through that region.

6893: 5296:"Rat Bone Marrow-Derived Schwann-Like Cells Differentiated by the Optimal Inducers Combination on Microfluidic Chip and Their Functional Performance" 4529:

Huang, Ying; Hodko, Dalibor; Smolko, Daniel; Lidgard, Graham (2006). "Electronic Microarray Technology and Applications in Genomics and Proteomics".

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such, peptide microarrays have been used to complement protein microarrays in proteomics research and diagnostics. Protein microarrays usually use

3820:"Label-Free Determination of the Number of Biomolecules Attached to Cells by Measurement of the Cell's Electrophoretic Mobility in a Microchannel" 1647: 1999:

An integrated microfluidic device with a concentration gradient generator and individual cell chambers for studying dose-dependent effects of

1661:. This approach uses less energy and has high throughput, but has large reagent consumption and gas bubbles can form inside the flow channels. 6831: 5394:

Toh, Yi-Chin; Blagović, Katarina; Voldman, Joel (2010). "Advancing stem cell research with microtechnologies: opportunities and challenges".

4260:"A novel silicon membrane-based biosensing platform using distributive sensing strategy and artificial neural networks for feature analysis" 1642:

device has been developed using this architecture integrating microvalves, microheaters, temperature sensors, 380-nL reaction chambers, and

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Chamber-based architecture is the result of shrinking down of conventional PCR reactors, which is difficult to scale up. A four-layer glass-

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Fodor, S.; Read, J.; Pirrung, M.; Stryer, L; Lu, A.; Solas, D (1991). "Light-directed, spatially addressable parallel chemical synthesis".

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Seo, Dongjin; Neely, Ryan M.; Shen, Konlin; Singhal, Utkarsh; Alon, Elad; Rabaey, Jan M.; Carmena, Jose M.; Maharbiz, Michel M. (2016).

788:. Electrophoresis and microfluidics are highly synergistic because it is possible to use higher voltages in microchannels due to faster 5141:

Le, Kim; Tan, Christopher; Gupta, Shivani; Guhan, Trupti; Barkhordian, Hedieh; Lull, Jonathan; Stevens, Jennitte; Munro, Trent (2018).

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sequences, which is useful for expanded use of rare samples e.g.: stem cells, biopsies, circulating tumor cells. The reaction involves

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are some methods used to pattern biological molecules onto surfaces. Cell micropatterning can be done using microcontact patterning of

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device containing paper and the first microfluidic product to market. In 1990, Andreas Manz and H. Michael Widmer from Ciba-Geigy (now

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to a circuit of two recording electrodes and a single transistor on an implanted micro-device. An external transducer emits pulses of

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Carrilho, Emanuel; Phillips, Scott T.; Vella, Sarah J.; Martinez, Andres W.; Whitesides, George M. (2009). "Paper Microzone Plates".

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and valves. However, there are some drawbacks to using silicon-based devices in biomedical applications such as their high cost and

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device (Anal. Chem., DOI: 10.1021/ac3005633). Fan isolates different types of CTCs by using aptamers with different specificities.

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Manz, A.; Graber, N.; Widmer, H.M. (1990). "Miniaturized total chemical analysis systems: A novel concept for chemical sensing".

1503:. In general, there are three types of protein microarrays: functional, analytical or capture, and reverse-phase protein arrays. 1222: 4017:

Unger, Marc; Chou, Hou-Pu; Thorsen, Todd (2000). "Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography".

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or continuous-flow separation. In capillary electrophoresis, a long thin tube separates analytes by voltage as they migrate by

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and can run indefinitely, but analytes are diluted by a factor of two. For cell analysis, cells can be studied intact or after

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supported a series of microfluidic research programs in the 1990s after realizing there was a need to develop field-deployable

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Tapia, Victor E.; Ay, Bernhard; Volkmer, Rudolf (2009). "Exploring and Profiling Protein Function with Peptide Arrays".

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at the fixed edge of the cantilever) due to a change in surface stress. In mass sensing, the cantilever vibrates at its

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to manipulate fluid flow for different applications. Paper microfluidics have been applied in paper electrophoresis and

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microchip, which integrates a reagent multiplexer, a cell chamber with a thin-film heater layer, and a peristaltic pump.

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Takayama, S.; McDonald, J. C.; Ostuni, E.; Liang, M. N.; Kenis, P. J. A.; Ismagilov, R. F.; Whitesides, G. M. (1999).

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microwells and flipping them onto a substrate or another cell layer is a method of achieving precise spatial control.

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Schematic of a quake valve, with process fluid channel perpendicular and out of plane with the control fluid channel.

530: 5027: 3959:"High response speed microfluidic ice valves with enhanced thermal conductivity and a movable refrigeration source" 2569:. Microneedles of approximately 100μm can penetrate the skin barrier and deliver drugs to the underlying cells and 2310: 1218: 699: 7004: 1612:

production of short chimeric molecules. PCR chips serve to miniaturize the reaction environment to achieve rapid

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for the paralyzed. Extracellular microelectrodes have been patterned onto an inflatable helix-shaped plastic in

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industry. At the time, the application of MEMS to biology was limited because this technology was optimized for

6734: 6698: 2082: 2058: 2019:. Differentiation in stem cells is dependent on many factors, including soluble and biochemical factors, fluid 1857:

and temperature control systems on chip, microfluidic cell culturing can eliminate the need for incubators and

839: 749: 371: 310: 226: 37: 1491:. A protein microarray consists of a protein library immobilized on a substrate chip, usually glass, silicon, 169:. After this first bio-MEMS study, subsequent development in the field was slow for around 20 years. In 1985, 6898: 6671: 6618:

Shawgo, Rebecca S; Richards Grayson, Amy C; Li, Yawen; Cima, Michael J (2002). "Bio-MEMS for drug delivery".

2290:

cell organization and architecture can also direct stem cell differentiation using microfluidic gradients of

1429:. The light removes photolabile protecting groups from the selected exposure areas. Following de-protection, 1181:

that is measured by a working electrode. Amperometric biosensors have been used in bio-MEMS for detection of

433: 2113:

in microfluidics allows shear stresses to be varied systematically using channel geometry and flow rate via

4429:

Homola, Jiří (2008). "Surface Plasmon Resonance Sensors for Detection of Chemical and Biological Species".

2420: 691: 5542:"Culturing Aerobic and Anaerobic Bacteria and Mammalian Cells with a Microfluidic Differential Oxygenator" 4569:

Talapatra, Anupam; Rouse, Richard; Hardiman, Gary (2002). "Protein microarrays: challenges and promises".

1103:. Common transducer techniques include mechanical detection, electrical detection, and optical detection. 6729: 3396:

Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms

2106: 1418:, negatively charged DNA and molecular probes can be concentrated on energized electrodes for interaction 1206: 601:

single cell analysis, precise control of cellular microenvironment, as well as controlled integration of

3818:

Rubinsky, Boris; Aki, Atsushi; Nair, Baiju G.; Morimoto, Hisao; Kumar, D. Sakthi; Maekawa, Toru (2010).

3124:

Kopp, M. U.; de Mello, A. J.; Manz, A. (1998). "Chemical Amplification: Continuous-Flow PCR on a Chip".

6949: 6805: 4879:"Miniaturized PCR chips for nucleic acid amplification and analysis: latest advances and future trends" 1426: 355: 2140:

interactions induce changes in differentiation and self-renewal by the stiffness of the substrate via

1075:

Biosensors are devices that consist of a biological recognition system, called the bioreceptor, and a

859:, as well as quantitative predictions of the biological environment of cells and biochemical reactions 197:

in the last decades leading up to the 1990s had been limited due to the time and cost of running many

2243: 2220: 2066: 1744: 1643: 1588: 1576: 1565: 1437:

Using inkjet technology, nucleotides are printed onto a surface drop by drop to form oligonucleotides

1286: 1281:) in optical signal indicates a reaction has occurred. Fluorescence-based detection has been used in 1270: 1083:

with the bioreceptor causes an effect that the transducer can convert into a measurement, such as an

657:, the most notable being the commercialized pregnancy test, ClearBlue. Advantages of using paper for 598: 507: 299: 214: 6468: 3734:

Osborn, Jennifer L.; Lutz, Barry; Fu, Elain; Kauffman, Peter; Stevens, Dean Y.; Yager, Paul (2010).

428:

in bio-MEMS is attractive because they can be easily fabricated, compatible with micromachining and

6989: 6939: 6664: 2271:

Murine embryoid bodies in suspension culture after 24 hours of formation from embryonic stem cells.

2185: 2000: 1735:

with lower fluid velocities and lower throughput than their conventional macroscopic counterparts.

1657:

Continuous flow-based architecture moves the sample through different temperature zones to achieve

1319: 1298: 1056:

In a passive mixing element, mixing is achieved by temporal and spatial redistribution of incoming

731: 622: 222: 4821: 3180:"Patterning cells and their environments using multiple laminar fluid flows in capillary networks" 2648:

Sieben, Vincent J.; Debes-Marun, Carina S.; Pilarski, Linda M.; Backhouse, Christopher J. (2008).

6724: 4740:"Microfluidic Chip for Molecular Amplification of Influenza A RNA in Human Respiratory Specimens" 4735: 2628: 2595: 2416: 2231: 1972: 1120: 457: 6289:"A Conformal, Bio-Interfaced Class of Silicon Electronics for Mapping Cardiac Electrophysiology" 4075:"Incorporation of prefabricated screw, pneumatic, and solenoid valves into microfluidic devices" 903:

Appropriate packaging of microfluidic devices can make them suitable for wearable applications,

6994: 6883: 6851: 6782: 6463: 3342:

Bashir, Rashid (2004). "Bio-MEMS: state-of-the-art in detection, opportunities and prospects".

2363: 989: 102: 90: 86: 5229:

Huh, D.; Matthews, B. D.; Mammoto, A.; Montoya-Zavala, M.; Hsin, H. Y.; Ingber, D. E. (2010).

3515: 2259:

time of stem cells often disrupt the spatial organization imposed by these microtechnologies.

1995: 1360:

parameters in a single experiment. Some applications of genomic and proteomic microarrays are

851:

Flow in microchannels is laminar, which allows selective treatment of cells in microchannels,

6787: 3503: 2623:. In implantable bio-MEMS for drug delivery, it is important to consider device rupture and 2396: 2177: 2118: 1894: 1862: 1795: 1792: 1365: 1128: 915: 687: 614: 190: 154: 118: 114: 46: 1483:

transcripts often correlate poorly with the actual amount of protein synthesized. Secondly,

6959: 6627: 6358: 6184: 5864: 5307: 5242: 4751: 4380: 4328: 4026: 3970: 3898: 3831: 3600: 3548:

Bhatia, Sangeeta N.; Chen, Christopher S. (1999). "Tissue engineering at the micro-scale".

3455: 3403: 3191: 3133: 3027: 2959: 2608: 2478: 2247: 2197: 2193: 2169: 2153: 2137: 2078: 2033: 2024: 1753: 1639: 1627: 1622: 1233: 1100: 1005: 793: 626: 511: 477: 333: 278: 270: 206: 126: 98: 1865:. Subsequently, flow needs to be resumed in a way that does not produce large forces that 132: 8: 6918: 6888: 2474: 2445: 2408: 2388: 2318: 2141: 1886: 1850: 1538: 1523: 965: 760:

Electrokinetics have been exploited in bio-MEMS for separating mixtures of molecules and

578: 94: 6631: 6362: 6188: 5868: 5311: 5246: 4755: 4384: 4332: 4030: 3974: 3902: 3835: 3604: 3459: 3407: 3195: 3137: 3031: 2963: 2097:

is relevant in the stem cell differentiation of cardiovascular lineages as well as late

6557: 6489: 6390: 6321: 6288: 6269: 6216: 6156: 5828: 5811: 5795: 5776: 5574: 5541: 5338: 5295: 5271: 5230: 5163: 5142: 4903: 4878: 4782: 4739: 4657: 4624: 4401: 4368: 4298: 4196: 4157: 4130: 4099: 4074: 4050: 3991: 3958: 3929: 3887:"Fast Benchtop Fabrication of Laminar Flow Chambers for Advanced Microscopy Techniques" 3886: 3862: 3819: 3760: 3735: 3632: 3573: 3486: 3445: 3433: 3375: 3106: 3073:(1998). "Microfabricated microneedles: A novel approach to transdermal drug delivery". 2991: 2570: 2562: 2523: 2448:. Wireless recording of electrophysiological signals is possible through addition of a 1930: 1527: 1476: 1472: 1361: 1210: 1116: 1037: 908: 904: 852: 590: 409: 274: 234: 122: 6639: 5662: 5645: 4486: 3736:"Microfluidics without pumps: reinventing the T-sensor and H-filter in paper networks" 2407:, which have increased electrodes per unit volume, while addressing problems of thick 1301:

are subtypes of chemiluminescence. Surface plasmon resonance sensors can be thin-film

736: 649:

Paper microfluidics (sometimes called lab on paper) is the use of paper substrates in

140:

outlining and contrasting some aspects of the fields of bio-MEMS, lab-on-a-chip, μTAS.

6643: 6600: 6592: 6549: 6541: 6481: 6431: 6382: 6374: 6326: 6308: 6261: 6208: 6200: 6148: 6140: 6105: 6097: 6061: 6053: 6018: 5977: 5969: 5924: 5916: 5880: 5833: 5815: 5768: 5760: 5718: 5710: 5675: 5667: 5622: 5614: 5579: 5561: 5522: 5514: 5473: 5465: 5419: 5411: 5343: 5325: 5276: 5258: 5211: 5203: 5168: 5123: 5115: 5080: 5072: 4989: 4951: 4943: 4908: 4852: 4844: 4787: 4769: 4716: 4708: 4698: 4662: 4644: 4594: 4586: 4542: 4511: 4454: 4446: 4406: 4290: 4282: 4238: 4200: 4162: 4104: 4042: 3996: 3934: 3916: 3867: 3849: 3800: 3765: 3716: 3678: 3670: 3624: 3616: 3577: 3565: 3491: 3473: 3367: 3359: 3273: 3227: 3222: 3209: 3179: 3157: 3149: 3098: 3090: 3051: 3043: 2995: 2983: 2975: 2932: 2928: 2895: 2709: 2681: 2673: 2575: 2550: 2499: 2437: 1910: 1858: 1592: 1421:

Using photolithography, a light exposure pattern is created on the substrate using a

1397: 1315: 1266: 887: 813: 801: 638: 429: 178: 74: 70: 66: 6273: 6160: 5780: 4302: 4054: 3636: 3379: 3110: 2514:

onto surgical tools also allows tactile feedback for the surgeon, identification of

2242:. Manipulating cell seeding density is a common biological technique in controlling 1983:

layer are cyclically stretched by applied vacuum on adjacent microchannels to mimic

1836:

technology is unable to efficiently allow combinatorial testing of drug candidates,

1408:

Using gel pads, prefabricated oligonucleotides are attached to patches of activated

149: 6954: 6826: 6635: 6584: 6561: 6533: 6493: 6473: 6421: 6366: 6316: 6300: 6251: 6243: 6220: 6192: 6132: 6089: 6045: 6008: 5959: 5951: 5908: 5872: 5852: 5823: 5807: 5752: 5702: 5657: 5606: 5569: 5553: 5504: 5455: 5447: 5403: 5333: 5315: 5266: 5250: 5195: 5158: 5150: 5107: 5064: 4981: 4935: 4898: 4890: 4836: 4777: 4759: 4690: 4652: 4636: 4578: 4534: 4501: 4438: 4396: 4388: 4344: 4336: 4274: 4230: 4192: 4152: 4142: 4094: 4086: 4034: 3986: 3978: 3924: 3906: 3857: 3839: 3792: 3755: 3747: 3708: 3662: 3608: 3557: 3481: 3463: 3411: 3351: 3265: 3217: 3199: 3141: 3082: 3035: 2967: 2924: 2665: 2599: 2527: 2515: 2470: 2449: 2441: 2424: 2400: 2322: 2239: 2216: 2189: 2181: 1548: 1389: 1178: 1158: 867: 834: 711: 670: 650: 610: 594: 586: 574: 519: 461: 449: 445: 387: 254: 246: 242: 230: 50: 41:. Bio-MEMS have considerable overlap, and is sometimes considered synonymous, with 6394: 5646:"Cell Shape, Cytoskeletal Tension, and RhoA Regulate Stem Cell Lineage Commitment" 3145: 2708:. Bellingham, Wash., USA: SPIE—The International Society for Optical Engineering. 2558: 2172:

interaction studies. It has been found by using micro-contact printing to control

2012: 332:

are key areas of research in improving bio-MEMS as replacements or complements to

6703: 6687: 6426: 6409: 6304: 6013: 5996: 5320: 4764: 4487:"An introduction to DNA chips: principles, technology, applications and analysis" 4038: 3911: 3844: 3468: 2604: 2507: 2433: 2347: 2161: 2149: 2110: 1980: 1976: 1968: 1964: 1960: 1926: 1917:

activated to manipulate cells across the chip. This platform has been adopted by

1914: 1812: 1757: 1522:

to profile protein or antibody expression in serum. These arrays can be used for

1415: 1385: 1377: 1306: 1294: 1162: 1123:. This results in bending of the cantilever that is measurable either optically ( 919: 773: 765: 741: 707: 662: 634: 630: 562: 537: 469: 465: 436:

and can be integrated into systems that use optical detection techniques such as

379: 286: 58: 4694: 4538: 4234: 3269: 1560: 1273:. Fluorescence-based optical techniques use markers that emit light at specific 914:

An interesting approach combining electrokinetic phenomena and microfluidics is

6841: 6810: 6759: 6708: 5641: 4258:

Wu, Z; Choudhury, Khujesta; Griffiths, Helen; Xu, Jinwu; Ma, Xianghong (2012).

3415: 3355: 3260:

Nguyen, Nam -Trung (2006). "5 Fabrication Issues of Biomedical Micro Devices".

3184:

Proceedings of the National Academy of Sciences of the United States of America

3070: 2650:"An integrated microfluidic chip for chromosome enumeration using fluorescence 2607:

or require localized release and exposure at a target site. Examples include a

2384: 2380: 2351: 1748: 1728: 1658: 1608: 1604: 1500: 1484: 1409: 993: 927: 871: 769: 761: 753: 666: 602: 570: 367: 363: 210: 198: 6477: 6247: 5012:

Patel, Prachi (2012). "Paper Diagnostic Tests Could Save Thousands of Lives".

4840: 4278: 3561: 2549:

microneedles patch is less invasive compared to conventional drug delivery by

1897:

measurements, but collection and detection is correspondingly more difficult.

1261:

in a miniaturized portable format on the bio-MEMS. Optical detection includes

6983: 6647: 6596: 6545: 6537: 6485: 6378: 6312: 6265: 6204: 6144: 6101: 6057: 5973: 5920: 5884: 5819: 5764: 5714: 5671: 5618: 5565: 5518: 5469: 5415: 5329: 5262: 5207: 5119: 5076: 4947: 4848: 4773: 4712: 4648: 4590: 4582: 4450: 4286: 3920: 3853: 3674: 3620: 3569: 3534:

http://pubs.rsc.org/en/content/articlelanding/2013/lc/c3lc50945a#!divAbstract

3477: 3432:

Barbosa, Mário A.; Mandal, Kalpana; Balland, Martial; Bureau, Lionel (2012).

3363: 3213: 3153: 3094: 3047: 2979: 2950:

Whitesides, George M. (2006). "The origins and the future of microfluidics".

2936: 2677: 2583: 2566: 2412: 2334: 2287: 2275: 2173: 2125: 2102: 2098: 2028: 1906: 1890: 1837: 1803: 1732: 1688:

count within 20 minutes using the Pima point-of-care CD4 analyzer, in Uganda.

1613: 1568: 1534: 1302: 1137: 961: 883: 856: 826: 789: 715: 683: 674: 658: 618: 476:

can also be modified for specific applications. Specifically, the surface of

329: 293: 194: 182: 166: 62: 54: 42: 6370: 5509: 5492: 5294:

Yang, Yanmin; Tian, Xiliang; Wang, Shouyu; Zhang, Zhen; Lv, Decheng (2012).

5254: 5199: 3204: 3039: 1335: 6913: 6604: 6553: 6435: 6386: 6330: 6212: 6152: 6109: 6065: 5981: 5928: 5837: 5772: 5722: 5679: 5626: 5583: 5526: 5477: 5423: 5347: 5280: 5172: 5127: 5084: 4993: 4955: 4912: 4856: 4791: 4720: 4666: 4598: 4515: 4506: 4458: 4410: 4294: 4204: 4166: 4108: 4073:

Hulme, S. Elizabeth; Shevkoplyas, Sergey S.; Whitesides, George M. (2009).

4046: 4000: 3938: 3871: 3804: 3769: 3720: 3682: 3628: 3495: 3371: 3231: 2987: 2685: 2624: 2620: 2542: 2282: 2251: 2094: 2070: 2048:, as well as measuring and sorting stem cells by their protein expression. 2020: 2016: 1882: 1866: 1854: 1841: 1833: 1778:

disease with research on other, more well-funded areas of medical research.

1719: 1714: 1572: 1262: 1257:

A challenge in optical detection is the need for integrating detectors and

1242: 1111:

Mechanical detection in bio-MEMS is achieved through micro- and nano-scale

1092: 1057: 926:

and selectively activated. Manipulation of small fluid droplets occurs via

843: 437: 306: 238: 137: 61:

and integration of laboratory processes and experiments into single (often

53:

technologies made suitable for biological applications. On the other hand,

6022: 5215: 4392: 3161: 3102: 3055: 2465: 2069:

and related signaling pathways, most notably in the development of blood,

1579:

channel. The application of this example bio-MEMS is for amplification of

557:

are spatially constrained to the geometry of the fibronectin micropattern.

6256: 5738:"An extracellular matrix microarray for probing cellular differentiation" 4894: 4147: 2616: 2612: 2546: 2495: 2314: 2212: 2041: 1788: 1664: 1580: 1492: 1311: 1198: 1166: 1045: 654: 554: 541: 481: 375: 325: 266: 202: 6196: 5997:"Applications of a microfabricated device for evaluating sperm function" 3086: 2971: 1621:

surface-reagent interactions. For example, silicon substrates have good

768:, a charged species in a liquid moves under the influence of an applied 6856: 6777: 6123:

Buzsáki, György (2004). "Large-scale recording of neuronal ensembles".

5995:

Kricka LJ, Nozaki O, Heyner S, Garside WT, Wilding P (September 1993).

5964: 5407: 4985: 4349: 2453: 2404: 2392: 2359: 2256: 2200: 2122: 1984: 1944: 1940: 1885:

system has been developed to study osteogenic differentiation of human

1845: 1724: 1668: 1430: 1393: 1348: 1282: 1274: 1258: 1112: 1076: 1033: 875: 745: 703: 695: 582: 497: 395: 359: 110: 33: 6346: 6049: 5876: 5610: 5557: 5460: 5154: 5068: 4939: 4442: 4340: 4129:

Yu, Chia-Yen; Chang, Chin-Lung; Wang, Wau-Nan; Quake, Stephen (2011).

3982: 3796: 3712: 3666: 2518:

type via strain and density during cutting operations, and diagnostic

2065:

is an important biochemical factor to consider in differentiation via

6964: 6588: 6524:

Nuxoll, E.; Siegel, R. (2009). "Bio-MEMS devices for drug delivery".

6093: 5955: 5912: 5796:"Cell patterning chip for controlling the stem cell microenvironment" 5756: 5706: 5451: 5111: 4640: 4090: 3751: 2669: 2235: 2165: 2114: 2045: 2008: 1975:

and the lungs. Organ-level lung functions have been reconstituted on

1878: 1808: 1702: 1651: 1617: 1422: 1229: 1186: 1132: 1070: 969: 923: 809: 797: 679: 485: 383: 174: 162: 3612: 3434:"Thermoresponsive Micropatterned Substrates for Single Cell Studies" 2321:

improve livestock. However, the efficiency of these technologies in

1782: 1616:

and fast mixing due to the larger surface-to-volume ratio and short

1446: 209:, which started in October 1990, created demand for improvements in 6769: 6136: 2649: 2587: 2519: 2299: 2295: 2291: 2204: 2145: 2074: 2037: 1922: 1710: 1706: 1519: 1381: 1344: 1246: 1088: 489: 408:, silicon-based bio-MEMS can be readily functionalized to minimize 317: 186: 106: 78: 6656: 3450: 2647: 2176:

area that that switch in osteogenic / adipogenic lineage in human

1943:

have been patterned to co-culture at specific cell densities with

1526:, monitoring of protein quantities, monitoring activity states in 2591: 2579: 2491: 2486: 2208: 2044:

modifications between stem cells and their daughter cells affect

1952: 1935: 1870: 1799: 1533:

Reverse-phase protein arrays test replicates of cell lysates and

1459: 1401: 1190: 1182: 1146: 1080: 931: 897: 893: 781: 566: 502: 473: 453: 425: 421: 404: 399: 321: 258: 170: 82: 5228: 1364:, identifying disease risk, and predicting therapy efficacy for 1025: 506:

applications. The most common polymers used in bio-MEMS include

6797: 6751: 2531: 2511: 2343: 2330: 2192:

can also be used to cross-link cell-seeded photo-polymerizable

2062: 1512: 1352: 1170: 1096: 1087:. The most common bioreceptors used in biosensing are based on 545: 4689:. Methods in Molecular Biology. Vol. 570. pp. 3–17. 1791:

and his team at the University of Florida involves the use of

951: 930:, which is the phenomenon where an electric field changes the 605:

into appropriate multi-cellular architectures to recapitulate

217:

thus became a focus for chemical and DNA separation. Thirdly,

6934: 5736:

Flaim, Christopher J; Chien, Shu; Bhatia, Sangeeta N (2005).

5639: 5054: 3782: 3068: 2429: 2355: 2011:

engineering is to be able to control the differentiation and

1948: 1925:

for cell line development in the biopharmaceutical industry.

1918: 1893:

cultures, the collected concentrations are higher for better

1290: 1238: 1214: 1174: 1124: 1041: 262: 218: 49:. Bio-MEMS is typically more focused on mechanical parts and 6617: 2337:

have been applied in these technologies to better mimic the

2117:, as demonstrated by using arrays of perfusion chambers for 1099:

interactions, cellular interactions, and interactions using

980: 972:

mold, making it an entirely additive manufacturing process.

752:

and cells are moved along the microchannel by an applied DC

269:

that were not compatible with biological material. In 1993,

161:

In 1967, S. B. Carter reported the use of shadow-evaporated

6944: 6173: 5493:"In Vitro Zonation and Toxicity in a Hepatocyte Bioreactor" 4625:"Protein microarrays: high-throughput tools for proteomics" 3177: 2369: 2267: 2262: 1971:

where multiple vascularized tissues interface, such as the

1956: 1496: 1488: 1480: 1454: 1356: 1355:

analysis faster and cheaper, as well as identify activated

1194: 1127:

reflection into a four-position detector) or electrically (

515: 493: 391: 250: 16: 6611: 5897: 5540:

Lam, Raymond H. W.; Kim, Min-Cheol; Thorsen, Todd (2009).

4623:

Stoevesandt, Oda; Taussig, Michael J; He, Mingyue (2009).

4072: 3698: 3431: 3392: 1963:

detoxification. Similarly, integrating microfluidics with

1518:

Analytical or capture protein arrays display antigens and

1339:

Affymetrix GeneChip is an example of a genomic microarray.

432:

methods, as well as have low cost. Many polymers are also

6454:

Rebello, K.J. (2004). "Applications of MEMS in Surgery".

6078: 5994: 5794:

Rosenthal, Adam; Macdonald, Alice; Voldman, Joel (2007).

5793: 5436: 4971: 4733: 4618: 4616: 4614: 4612: 4610: 4608: 4318: 4182: 1685: 1600: 1202: 1152: 785: 777: 292:

In 1998, the first solid microneedles were developed for

5941: 3885:

Ulijn, Rein; Courson, David S.; Rock, Ronald S. (2009).

3069:

Henry, Sebastien; McAllister, Devin V.; Allen, Mark G.;

1648:

reverse transcription polymerase chain reaction (RT-PCR)

412:, but the brittleness of silicon remains a major issue. 5851:

Lee, Philip J.; Hung, Paul J.; Shaw, Robin; Jan, Lily;

5185: 5048: 4528: 3817: 3694: 3692: 3591:

Voldman, Joel (2003). "Bio-MEMS: Building with cells".

2109:

or rotating cone apparatuses in on-off scenarios only.

1293:

generation by energy release from a chemical reaction.

805: 6233: 5787: 5692: 5596: 4605: 4568: 4257: 3173: 3171: 3017: 2403:

has led to the development of Michigan probes and the

1064: 1061:

shortening the characteristic diffusion length scale.

842:, they flow in separate flow lanes (no mixing) due to 378:, chemical detectors, separation capillaries, mixers, 6410:"Wireless Recording in the Peripheral Nervous System" 5231:"Reconstituting Organ-Level Lung Functions on a Chip" 4564: 4562: 4560: 4558: 2305: 2215:

on stem cells is more advantageous than conventional

984:

Diagram of an ice valve with Peltier cooling element.

892:

Microfluidic devices consume much smaller amounts of

6620:

Current Opinion in Solid State and Materials Science

4622: 3776: 3733: 3689: 3427: 3425: 2703: 2641: 2619:

and microchips with gold-capped drug reservoirs for

2302:-inducing factors, as well as self-renewal factors. 1330: 1305:

or gratings that measure the resonance behaviour of

1165:, especially in comparison to optical detection. In 398:

facilities, high material and processing costs make

6519: 6517: 6515: 6513: 6511: 6509: 6507: 6505: 6503: 6407: 6167: 6035: 5389: 5387: 5385: 5383: 5381: 5379: 5377: 5097: 4815: 4813: 4811: 4809: 4807: 4805: 4803: 4801: 4480: 4478: 4476: 4474: 4472: 4470: 4468: 4367:Arlett, J.L.; Myers, E.B. M.; Roukes, M.L. (2011). 3168: 2350:. Bio-MEMS devices have been developed to evaluate 1939:conditions and 3D natural structure. Specifically, 1675: 918:. In digital microfluidics, a substrate surface is 7000:Microelectronic and microelectromechanical systems 5393: 5375: 5373: 5371: 5369: 5367: 5365: 5363: 5361: 5359: 5357: 4967: 4965: 4925: 4555: 4362: 4360: 4314: 4312: 3062: 2411:causing damage during implantation and triggering 1929:co-cultures have also contributed to bio-MEMS for 1869:the cells off the substrate. Dispensing fluids by 1743:Microfluidic sample separation can be achieved by 1466: 390:. Due to being single-use only, larger than their 305:In 1999, the first demonstration of heterogeneous 181:still used today that can be considered the first 20:An example of a bio-MEMS device is this automated 6526:IEEE Engineering in Medicine and Biology Magazine 6286: 5891: 5686: 5644:; Bhadriraju, Kiran; Chen, Christopher S (2004). 5633: 5430: 5293: 4369:"Comparative advantages of mechanical biosensors" 4366: 4225:Vo-Dinh, Tuan (2006). "Biosensors and Biochips". 4178: 4176: 4068: 4066: 4064: 3543: 3541: 3422: 3386: 2706:Fundamentals of bio-MEMS and medical microdevices 2027:interactions, cell-cell interactions, as well as 1822: 1783:Circulating Tumor Cell (CTC) Capture Technologies 1530:, and profiling antibody repertories in diseases. 1161:detection are easily adapted for portability and 6981: 6574: 6500: 6227: 6072: 5735: 5188:Journal of Biomaterials Science, Polymer Edition 4872: 4870: 4868: 4866: 4798: 4465: 4128: 4016: 3884: 3878: 3123: 2914: 2188:can determine traction forces exerted on cells. 1277:and the presence or enhancement/reduction (e.g. 896:, can be made to require only a small amount of 874:, and microoptics onto the same platform allows 838:When multiple solutions are added into the same 6029: 5935: 5354: 5222: 5179: 5140: 4962: 4919: 4357: 4309: 3811: 3527: 3525: 3013: 3011: 3009: 3007: 3005: 2502:layer-by-layer microfabrication techniques for 1979:devices where a porous membrane and the seeded 1223:light-addressable potentiometric sensors (LAPS) 878:, which reduces human error and operation costs 354:Conventional micromachining techniques such as 6832:Radio-frequency microelectromechanical systems 6449: 6447: 6445: 6280: 5850: 5729: 4684: 4680: 4678: 4676: 4522: 4220: 4218: 4216: 4214: 4173: 4061: 3957:Si, Chaorun; Hu, Songtao; Wu, Weichao (2017). 3727: 3538: 3337: 3335: 3333: 3331: 3329: 3327: 3325: 3323: 3321: 3319: 3317: 3315: 3313: 3311: 3309: 2374: 1626:inhibits the reaction. Polymers, particularly 1215:ion-sensitive field effect transistors (ISFET) 402:-based bio-MEMS less economically attractive. 6672: 5539: 5149:. Advance online publication (6): 1438–1446. 4863: 4727: 4424: 4422: 4420: 3307: 3305: 3303: 3301: 3299: 3297: 3295: 3293: 3291: 3289: 3255: 3253: 3251: 3249: 3247: 3245: 3243: 3241: 2943: 2908: 2223:and lower requirement of expensive reagents. 1020: 673:action. A severe disadvantage of paper-based 597:. Biological micropatterning can be used for 6523: 6401: 5287: 5007: 5005: 5003: 4819: 4484: 4012: 4010: 3952: 3950: 3948: 3648: 3646: 3522: 3002: 2699: 2697: 2695: 2440:, and electronic tattoos for measuring skin 2067:hypoxia-induced transcription factors (HIFs) 1770:devices, in order to increase their utility. 1756:, continuous-flow magnetic separations, and 694:, and dilution; the common 96- and 384-well 6442: 6116: 5844: 5091: 4673: 4211: 4135:International Journal of Molecular Sciences 3652: 3584: 1684:A midwife draws blood to measure patients' 1325: 1044:by sonication is intense local heating and 6679: 6665: 6343: 5988: 5533: 5028:"Microfluidic Devices Capture Tumor Cells" 4417: 4124: 4122: 4120: 4118: 3547: 3286: 3238: 2949: 2234:is regulated by both interactions between 1450:Differential comparison in cDNA microarray 1106: 1051: 748:are set at both the inlet and outlet of a 358:, dry etching, deep reactive ion etching, 6847:Biological microelectromechanical systems 6467: 6425: 6337: 6320: 6255: 6012: 5963: 5827: 5661: 5590: 5573: 5508: 5484: 5459: 5337: 5319: 5270: 5162: 5134: 5000: 4902: 4876: 4822:"Microfluidic DNA amplification—A review" 4781: 4763: 4656: 4505: 4400: 4348: 4156: 4146: 4098: 4007: 3990: 3945: 3928: 3910: 3861: 3843: 3759: 3643: 3485: 3467: 3449: 3221: 3203: 2692: 2460: 2226: 1763: 1376:Oligonucleotide chips are microarrays of 641:, and electrochemically active surfaces. 105:. Some of its major applications include 6568: 2885: 2883: 2881: 2879: 2877: 2875: 2873: 2871: 2869: 2867: 2865: 2863: 2861: 2859: 2857: 2855: 2853: 2851: 2849: 2847: 2845: 2843: 2841: 2839: 2837: 2835: 2833: 2831: 2829: 2827: 2825: 2823: 2821: 2819: 2817: 2815: 2813: 2811: 2809: 2807: 2805: 2803: 2801: 2799: 2797: 2795: 2793: 2791: 2789: 2787: 2785: 2783: 2781: 2779: 2777: 2775: 2773: 2771: 2769: 2767: 2765: 2763: 2761: 2759: 2757: 2755: 2753: 2751: 2749: 2747: 2745: 2611:microfluidic device implanted under the 2541: 2464: 2370:Bio-MEMS in medical implants and surgery 2266: 2263:Embryoid body formation and organization 2238:and interactions between stem cells and 2131: 1994: 1990: 1802:, which are attached to the channels of 1679: 1559: 1445: 1371: 1351:microarrays are to make high-throughput 1334: 1289:on a chip devices. Chemiluminescence is 1024: 979: 950: 934:of an electrolyte droplet on a surface. 833: 735: 529: 415: 148: 131: 15: 6453: 6122: 4820:Zhang, Yonghao; Ozdemir, Pinar (2009). 4224: 4115: 3590: 3117: 2743: 2741: 2739: 2737: 2735: 2733: 2731: 2729: 2727: 2725: 2184:of microposts and measurement of their 1738: 999: 937: 525: 500:, allowing for better cell adhesion in 6982: 4428: 4251: 3956: 3341: 3259: 2615:for drug delivery to the eye to treat 2534:content, and chemical concentrations. 2164:, and mask spraying have been used in 2051: 1696: 1425:or virtual photomask projected from a 1279:fluorescence resonance energy transfer 1153:Electrical and electrochemical sensors 700:automated liquid handling and analysis 6660: 5490: 5011: 4531:BioMEMS and Biomedical Nanotechnology 4227:BioMEMS and Biomedical Nanotechnology 3262:BioMEMS and Biomedical Nanotechnology 2889: 2498:have been made possible by metal and 2203:to optimize combinatorial effects of 2196:for three-dimensional studies. Using 2088: 1967:co-cultures has enabled modelling of 1595:technique that enables the selective 1011: 577:have been used in the development of 394:counterparts, and the requirement of 251:microelectromechanical systems (MEMS) 189:), Switzerland first coined the term 153:Andreas Manz, one of the pioneers of 4185:Ultrasound in Medicine & Biology 2722: 2590:, are poorly soluble and need to be 349: 309:for selective treatment of cells in 6686: 2565:systems are bio-MEMS applicable to 1065:Bio-MEMS as Miniaturized Biosensors 776:has been used to fractionate small 690:, size-based molecular extraction, 370:have been used in bio-MEMS to make 298:In 1998, the first continuous-flow 47:micro total analysis systems (μTAS) 13: 6837:Microoptoelectromechanical systems 5812:10.1016/j.biomaterials.2007.03.023 5020: 4877:Zhang, Chunshun; Xing, Da (2007). 4197:10.1016/j.ultrasmedbio.2005.05.005 3075:Journal of Pharmaceutical Sciences 2391:signals to study disease, improve 2311:Assisted reproductive technologies 2306:Assisted reproductive technologies 1667:eliminates sample/reagent surface 1441: 1252: 1145:optically detectable label on the 804:. Isoelectric focusing requires a 725: 665:in bio-MEMS include its low cost, 229:for the detection of chemical and 191:micro total analysis system (μTAS) 14: 7016: 5640:McBeath, Rowena; Pirone, Dana M; 2917:Sensors and Actuators B: Chemical 1331:Genomic and proteomic microarrays 1219:Chemical field-effect transistors 1201:, as well as for applications in 1177:reaction causes a redox electron 808:gradient (usually generated with 2537: 2494:, microneedle arrays and tissue 2383:is to interface with the body's 2346:can be integrated for real-time 2148:interacting with ECM molecules. 1676:Point-of-care-diagnostic devices 1312:food quality and safety analysis 820: 744:experiment example: Two conical 565:of biological materials such as 277:chemist, introduced inexpensive 5032:Chemical & Engineering News 4131:"Microfluidic Mixing: A Review" 2015:of pluripotency stem cells for 1827: 1589:polymerase chain reaction (PCR) 1571:system with thin film heaters, 1509:post-translational modification 1467:Peptide and protein microarrays 1271:surface plasmon resonance (SPR) 996:was used as the cooling agent. 946: 907:, and portable applications in 796:is the separation of proteins, 6699:Microelectromechanical systems 6293:Science Translational Medicine 3344:Advanced Drug Delivery Reviews 2358:selection, as well as prevent 1823:Bio-MEMS in tissue engineering 460:for applications where strong 448:. Moreover, many polymers are 265:wafers and used solvent-based 129:and implantable microdevices. 38:microelectromechanical systems 1: 6640:10.1016/S1359-0286(02)00032-3 5663:10.1016/S1534-5807(04)00075-9 3146:10.1126/science.280.5366.1046 2704:Steven S. Saliterman (2006). 2635: 2180:can be cell shape dependent. 975: 780:, charged organic molecules, 339: 241:. Researchers started to use 6427:10.1016/j.neuron.2016.06.034 6305:10.1126/scitranslmed.3000738 5321:10.1371/journal.pone.0042804 4765:10.1371/journal.pone.0033176 4039:10.1126/science.288.5463.113 3912:10.1371/journal.pone.0006479 3845:10.1371/journal.pone.0015641 3469:10.1371/journal.pone.0037548 2929:10.1016/0925-4005(90)80209-I 2598:. Bio-MEMS technology using 2436:alone for measuring cardiac 2107:parallel-plate flow chambers 1951:-specific functions such as 1731:and can be implemented into 1583:RNA in respiratory specimens 1555: 764:using electrical fields. In 561:Microscale manipulation and 344: 157:at MicroTAS conference 2007. 7: 4695:10.1007/978-1-60327-394-7_1 4629:Expert Review of Proteomics 4539:10.1007/978-0-387-25843-0_1 4485:Gabig M, Wegrzyn G (2001). 4235:10.1007/978-0-387-25845-4_1 3270:10.1007/978-0-387-25845-4_5 2397:monitor clinical parameters 2375:Implantable microelectrodes 800:, and cells with different 10: 7021: 6806:Digital micromirror device 6014:10.1093/clinchem/39.9.1944 3416:10.1016/j.nimb.2011.07.065 3356:10.1016/j.addr.2004.03.002 2504:minimally invasive surgery 2473:with temperature sensors, 2387:for recording and sending 1427:digital micromirror device 1068: 1021:Sonication Mixing Elements 824: 729: 466:electrophoretic separation 207:Human Genome Project (HGP) 144: 6927: 6876: 6869: 6819: 6796: 6768: 6750: 6743: 6717: 6694: 6478:10.1109/JPROC.2003.820536 6248:10.1007/s00542-004-0376-5 4841:10.1016/j.aca.2009.02.038 4279:10.1007/s10544-011-9587-6 2894:. Boca Raton: CRC Press. 2596:intranasal administration 2040:determine cell fate, how 1745:capillary electrophoresis 1644:capillary electrophoresis 1471:The motivation for using 1079:. The interaction of the 623:self-assembled monolayers 300:polymerase chain reaction 215:Capillary electrophoresis 205:equipment. Secondly, the 119:point-of-care diagnostics 6940:Shallow trench isolation 6538:10.1109/MEMB.2008.931014 6236:Microsystem Technologies 4736:Klapperich, Catherine M. 4583:10.1517/14622416.3.4.527 2892:Introduction to bio-MEMS 2421:brain–computer interface 2379:The goal of implantable 2329:production of mammalian 2081:membranes to gas-filled 1607:of the DNA sequence and 1326:Bio-MEMS for diagnostics 1320:environmental monitoring 1299:electrochemiluminescence 876:automated device control 732:Electrokinetic phenomena 706:readers. Techniques for 644: 223:US Department of Defense 199:chromatographic analyses 6725:Interdigital transducer 6456:Proceedings of the IEEE 6371:10.1126/science.1206157 6347:"Epidermal Electronics" 5857:Applied Physics Letters 5255:10.1126/science.1188302 5200:10.1163/156856298X00695 4321:Applied Physics Letters 3562:10.1023/A:1009949704750 3550:Biomedical Microdevices 3205:10.1073/pnas.96.10.5545 3040:10.1126/science.1990438 2481:is a surgical bio-MEMS. 1909:culture on an array of 1807:and the development of 1269:-based techniques, and 1107:Micromechanical sensors 1052:Passive Mixing Elements 458:electrically insulating 450:biologically compatible 31:is an abbreviation for 7005:Biomedical engineering 6884:Surface micromachining 6783:Scratch drive actuator 5497:Toxicological Sciences 5147:Biotechnology Progress 4883:Nucleic Acids Research 4829:Analytica Chimica Acta 4507:10.18388/abp.2001_3896 2890:Folch, Albert (2013). 2554: 2482: 2461:Microtools for surgery 2364:in-vitro fertilization 2272: 2244:cell–cell interactions 2227:Cell–cell interactions 2178:mesenchymal stem cells 2158:micro-contact printing 2119:mesenchymal stem cells 2004: 1796:nucleic acid sequences 1764:Outstanding Challenges 1689: 1654:detection sensitivity. 1634:) chip architectures. 1584: 1575:, and continuous flow 1564:Continuous flow-based 1451: 1340: 1030: 985: 956: 853:mathematical modelling 847: 757: 722:, and wax patterning. 558: 484:with elements such as 464:are necessary such as 452:, chemically inert to 253:as inherited from the 158: 141: 103:biomedical engineering 91:mechanical engineering 87:electrical engineering 25: 5510:10.1093/toxsci/kfi052 5491:Allen, J. 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(2005). 4393:10.1038/nnano.2011.44 4373:Nature Nanotechnology 2629:fibrous encapsulation 2594:immediately prior to 2545: 2487:surgical applications 2468: 2413:foreign-body reaction 2270: 2132:Cell–ECM interactions 2034:transcription factors 1998: 1991:Stem-cell engineering 1895:signal-to-noise ratio 1877:can be replaced with 1683: 1563: 1449: 1372:Oligonucleotide chips 1366:personalized medicine 1338: 1028: 983: 954: 916:digital microfluidics 855:of flow patterns and 837: 739: 688:hydrodynamic focusing 615:microcontact printing 533: 434:optically transparent 416:Plastics and polymers 152: 135: 115:molecular diagnostics 19: 6960:Silicon on insulator 6038:Analytical Chemistry 5599:Analytical Chemistry 5546:Analytical Chemistry 5057:Analytical Chemistry 4928:Analytical Chemistry 4148:10.3390/ijms12053263 3785:Analytical Chemistry 3701:Analytical Chemistry 3655:Analytical Chemistry 2578:(if the material is 2405:Utah electrode array 1887:embryonic stem cells 1859:tissue culture hoods 1804:microfluidic devices 1754:isoelectric focusing 1739:Sample fractionation 1623:thermal conductivity 1513:enzymatic activities 1234:electrical impedance 1101:biomimetic materials 1000:Prefabricated Valves 938:BioMEMs Flow Control 909:developing countries 794:Isoelectric focusing 718:, ink jet printing, 627:extracellular matrix 526:Biological materials 496:to decrease surface 271:George M. Whitesides 233:that were potential 127:single cell analysis 99:chemical engineering 6919:3D microfabrication 6889:Bulk micromachining 6632:2002COSSM...6..329S 6363:2011Sci...333..838K 6197:10.1038/nature04970 6189:2006Natur.442..164H 6125:Nature Neuroscience 5869:2005ApPhL..86v3902L 5396:Integrative Biology 5312:2012PLoSO...742804T 5247:2010Sci...328.1662H 5241:(5986): 1662–1668. 5014:Scientific American 4756:2012PLoSO...733176C 4687:Peptide Microarrays 4385:2011NatNa...6..203A 4333:2006ApPhL..89v4104T 4267:Biomed Microdevices 4031:2000Sci...288..113U 3975:2017NatSR...740570S 3903:2009PLoSO...4.6479C 3836:2010PLoSO...515641A 3605:2003NatMa...2..433V 3460:2012PLoSO...737548M 3408:2012NIMPB.273..161I 3264:. pp. 93–115. 3196:1999PNAS...96.5545T 3138:1998Sci...280.1046K 3132:(5366): 1046–1048. 3032:1991Sci...251..767F 2972:10.1038/nature05058 2964:2006Natur.442..368W 2510:. Incorporation of 2475:electrocardiography 2142:mechanotransduction 2052:Biochemical factors 1973:blood–brain barrier 1701:In blood analysis, 1697:Sample conditioning 1539:biomarker discovery 1528:signalling pathways 1524:biomarker discovery 1479:is firstly because 1477:protein microarrays 1316:medical diagnostics 1265:-based techniques, 1121:surface free energy 966:Stanford University 884:cross contamination 686:operations such as 629:proteins, cellular 285:In 1991, the first 95:optical engineering 43:lab-on-a-chip (LOC) 6894:HAR micromachining 5650:Developmental Cell 5408:10.1039/c0ib00004c 4986:10.1039/c2lc40630f 4895:10.1093/nar/gkm389 3963:Scientific Reports 3514:has generic name ( 3071:Prausnitz, Mark R. 2571:interstitial fluid 2555: 2483: 2454:ultrasonic energy} 2273: 2089:Fluid shear stress 2005: 1931:tissue engineering 1863:hydrodynamic traps 1690: 1585: 1452: 1362:neonatal screening 1341: 1133:resonant frequency 1031: 1012:Micro-scale Mixing 986: 957: 848: 802:isoelectric points 758: 591:tissue engineering 559: 410:protein adsorption 388:bioincompatibility 302:chip was developed 289:chip was developed 159: 142: 123:tissue engineering 57:is concerned with 26: 6977: 6976: 6973: 6972: 6865: 6864: 6357:(6044): 838–843. 6183:(7099): 164–171. 6050:10.1021/ac020579e 5877:10.1063/1.1938253 5806:(21): 3208–3216. 5642:Nelson, Celeste M 5611:10.1021/ac049837t 5605:(18): 5257–5264. 5558:10.1021/ac9006864 5552:(14): 5918–5924. 5194:(11): 1137–1160. 5155:10.1002/btpr.2690 5069:10.1021/ac071311w 5063:(22): 8557–8563. 4980:(18): 3249–3266. 4940:10.1021/ac061058k 4934:(23): 7997–8003. 4889:(13): 4223–4237. 4704:978-1-60327-393-0 4548:978-0-387-25564-4 4533:. pp. 3–21. 4494:Acta Biochim. Pol 4443:10.1021/cr068107d 4341:10.1063/1.2388925 4244:978-0-387-25566-8 4229:. pp. 1–20. 4025:(5463): 113–116. 3983:10.1038/srep40570 3797:10.1021/ac900847g 3791:(15): 5990–5998. 3746:(20): 2659–2665. 3713:10.1021/ac9013989 3667:10.1021/ac9020193 3350:(11): 1565–1586. 3279:978-0-387-25566-8 3190:(10): 5545–5548. 3087:10.1021/js980042+ 3026:(4995): 767–773. 2958:(7101): 368–373. 2901:978-1-4398-1839-8 2551:hypodermic needle 2438:electrophysiology 2425:cochlear implants 2240:membrane proteins 2221:higher throughput 2003:inducing factors. 1902:microscopy assays 1875:robotic pipetting 1758:molecular sieving 1703:white blood cells 1593:molecular biology 1591:is a fundamental 1398:inkjet technology 1267:chemiluminescence 1207:DNA hybridization 1149:or bioreceptors. 1085:electrical signal 888:rapid prototyping 814:Dielectrophoresis 639:dielectrophoresis 595:artificial organs 579:cell-based arrays 470:Surface chemistry 462:electrical fields 442:UV/Vis absorbance 430:rapid prototyping 350:Silicon and glass 239:terrorist threats 231:biological agents 75:clinical sciences 71:material sciences 67:chemical analysis 7012: 6955:Photolithography 6874: 6873: 6827:Millipede memory 6788:Thermal actuator 6748: 6747: 6718:Basic structures 6681: 6674: 6667: 6658: 6657: 6652: 6651: 6615: 6609: 6608: 6589:10.1039/b804690e 6572: 6566: 6565: 6521: 6498: 6497: 6471: 6451: 6440: 6439: 6429: 6405: 6399: 6398: 6341: 6335: 6334: 6324: 6284: 6278: 6277: 6259: 6242:(6–7): 478–483. 6231: 6225: 6224: 6171: 6165: 6164: 6120: 6114: 6113: 6094:10.1039/b504397m 6076: 6070: 6069: 6044:(7): 1671–1675. 6033: 6027: 6026: 6016: 5992: 5986: 5985: 5967: 5956:10.1039/b903753e 5939: 5933: 5932: 5913:10.1039/b618439a 5895: 5889: 5888: 5848: 5842: 5841: 5831: 5791: 5785: 5784: 5757:10.1038/nmeth736 5742: 5733: 5727: 5726: 5707:10.1039/b406953f 5690: 5684: 5683: 5665: 5637: 5631: 5630: 5594: 5588: 5587: 5577: 5537: 5531: 5530: 5512: 5488: 5482: 5481: 5463: 5452:10.1039/b417651k 5434: 5428: 5427: 5391: 5352: 5351: 5341: 5323: 5291: 5285: 5284: 5274: 5226: 5220: 5219: 5183: 5177: 5176: 5166: 5138: 5132: 5131: 5112:10.1039/b510901a 5095: 5089: 5088: 5052: 5046: 5045: 5039: 5038: 5024: 5018: 5017: 5009: 4998: 4997: 4969: 4960: 4959: 4923: 4917: 4916: 4906: 4874: 4861: 4860: 4826: 4817: 4796: 4795: 4785: 4767: 4731: 4725: 4724: 4682: 4671: 4670: 4660: 4641:10.1586/epr.09.2 4620: 4603: 4602: 4571:Pharmacogenomics 4566: 4553: 4552: 4526: 4520: 4519: 4509: 4491: 4482: 4463: 4462: 4431:Chemical Reviews 4426: 4415: 4414: 4404: 4364: 4355: 4354: 4352: 4316: 4307: 4306: 4264: 4255: 4249: 4248: 4222: 4209: 4208: 4191:(9): 1265–1277. 4180: 4171: 4170: 4160: 4150: 4141:(5): 3263–3287. 4126: 4113: 4112: 4102: 4091:10.1039/b809673b 4070: 4059: 4058: 4014: 4005: 4004: 3994: 3954: 3943: 3942: 3932: 3914: 3882: 3876: 3875: 3865: 3847: 3815: 3809: 3808: 3780: 3774: 3773: 3763: 3752:10.1039/c004821f 3731: 3725: 3724: 3696: 3687: 3686: 3650: 3641: 3640: 3593:Nature Materials 3588: 3582: 3581: 3545: 3536: 3529: 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6979: 6978: 6969: 6923: 6861: 6815: 6792: 6764: 6739: 6713: 6704:Microtechnology 6690: 6688:Microtechnology 6685: 6655: 6616: 6612: 6573: 6569: 6522: 6501: 6469:10.1.1.121.5772 6452: 6443: 6406: 6402: 6342: 6338: 6285: 6281: 6232: 6228: 6172: 6168: 6121: 6117: 6088:(11): 1229–32. 6077: 6073: 6034: 6030: 5993: 5989: 5940: 5936: 5896: 5892: 5849: 5845: 5792: 5788: 5740: 5734: 5730: 5691: 5687: 5638: 5634: 5595: 5591: 5538: 5534: 5489: 5485: 5435: 5431: 5402:(7–8): 305–25. 5392: 5355: 5292: 5288: 5227: 5223: 5184: 5180: 5139: 5135: 5096: 5092: 5053: 5049: 5036: 5034: 5026: 5025: 5021: 5010: 5001: 4970: 4963: 4924: 4920: 4875: 4864: 4824: 4818: 4799: 4732: 4728: 4705: 4683: 4674: 4621: 4606: 4567: 4556: 4549: 4527: 4523: 4489: 4483: 4466: 4427: 4418: 4365: 4358: 4317: 4310: 4262: 4256: 4252: 4245: 4223: 4212: 4181: 4174: 4127: 4116: 4071: 4062: 4015: 4008: 3955: 3946: 3883: 3879: 3816: 3812: 3781: 3777: 3732: 3728: 3697: 3690: 3651: 3644: 3613:10.1038/nmat936 3589: 3585: 3546: 3539: 3530: 3523: 3511: 3510: 3501: 3500: 3430: 3423: 3391: 3387: 3340: 3287: 3280: 3258: 3239: 3176: 3169: 3122: 3118: 3067: 3063: 3016: 3003: 2948: 2944: 2913: 2909: 2902: 2888: 2723: 2716: 2702: 2693: 2646: 2642: 2638: 2617:ocular diseases 2605:bioavailability 2540: 2520:catheterization 2508:robotic surgery 2463: 2434:surface tension 2381:microelectrodes 2377: 2372: 2348:quality control 2308: 2276:Embryoid bodies 2265: 2229: 2174:cell attachment 2162:inkjet printing 2150:Micropatterning 2134: 2111:Poiseuille flow 2091: 2061:relationships. 2054: 2001:differentiation 1993: 1981:epithelial cell 1959:synthesis, and 1911:photoconductors 1830: 1825: 1817:UNC Chapel Hill 1813:Steven A. Soper 1785: 1766: 1749:electro-osmotic 1741: 1699: 1678: 1659:thermal cycling 1605:thermal cycling 1558: 1485:DNA microarrays 1469: 1444: 1442:cDNA microarray 1416:microelectrodes 1386:microelectrodes 1374: 1333: 1328: 1307:surface plasmon 1295:Bioluminescence 1255: 1253:Optical sensors 1247:bacterial cells 1169:biosensors, an 1163:miniaturization 1159:electrochemical 1157:Electrical and 1155: 1109: 1073: 1067: 1054: 1023: 1014: 1002: 978: 949: 940: 866:Integration of 829: 823: 817:concentration. 774:Electrophoresis 766:electrophoresis 742:electrophoresis 734: 728: 726:Electrokinetics 708:micropatterning 663:electrophoresis 647: 635:optical tweezer 631:electrophoresis 599:high-throughput 549: 538:Micropatterning 528: 418: 352: 347: 342: 287:oligonucleotide 201:in parallel on 173:commercialized 167:cell attachment 147: 59:miniaturization 12: 11: 5: 7018: 7008: 7007: 7002: 6997: 6992: 6975: 6974: 6971: 6970: 6968: 6967: 6962: 6957: 6952: 6947: 6942: 6937: 6931: 6929: 6925: 6924: 6922: 6921: 6916: 6911: 6906: 6901: 6896: 6891: 6886: 6880: 6878: 6871: 6867: 6866: 6863: 6862: 6860: 6859: 6854: 6849: 6844: 6842:Microphotonics 6839: 6834: 6829: 6823: 6821: 6817: 6816: 6814: 6813: 6811:Optical switch 6808: 6802: 6800: 6794: 6793: 6791: 6790: 6785: 6780: 6774: 6772: 6766: 6765: 6763: 6762: 6760:Microbolometer 6756: 6754: 6745: 6741: 6740: 6738: 6737: 6732: 6727: 6721: 6719: 6715: 6714: 6712: 6711: 6709:Micromachinery 6706: 6701: 6695: 6692: 6691: 6684: 6683: 6676: 6669: 6661: 6654: 6653: 6626:(4): 329–334. 6610: 6583:(7): 1027–30. 6567: 6499: 6441: 6420:(3): 529–539. 6400: 6336: 6299:(24): 24ra22. 6279: 6226: 6166: 6137:10.1038/nn1233 6131:(5): 446–451. 6115: 6071: 6028: 5987: 5950:(17): 2591–5. 5934: 5890: 5863:(22): 223902. 5843: 5786: 5751:(2): 119–125. 5745:Nature Methods 5728: 5685: 5656:(4): 483–495. 5632: 5589: 5532: 5503:(1): 110–119. 5483: 5429: 5353: 5286: 5221: 5178: 5133: 5090: 5047: 5019: 4999: 4961: 4918: 4862: 4835:(2): 115–125. 4797: 4726: 4703: 4672: 4635:(2): 145–157. 4604: 4577:(4): 527–536. 4554: 4547: 4521: 4464: 4437:(2): 462–493. 4416: 4379:(4): 203–215. 4356: 4327:(22): 224104. 4308: 4250: 4243: 4210: 4172: 4114: 4060: 4006: 3944: 3877: 3830:(12): e15641. 3810: 3775: 3726: 3688: 3661:(1): 329–335. 3642: 3599:(7): 433–434. 3583: 3556:(2): 131–144. 3537: 3521: 3421: 3385: 3285: 3278: 3237: 3167: 3116: 3081:(8): 922–925. 3061: 3001: 2942: 2907: 2900: 2721: 2714: 2691: 2664:(12): 2151–6. 2654:hybridization" 2639: 2637: 2634: 2557:Microneedles, 2539: 2536: 2462: 2459: 2446:bioelectricity 2415:and electrode 2385:nervous system 2376: 2373: 2371: 2368: 2352:sperm motility 2313:help to treat 2307: 2304: 2264: 2261: 2228: 2225: 2133: 2130: 2090: 2087: 2053: 2050: 1992: 1989: 1977:lung-on-a-chip 1965:micropatterned 1927:Micropatterned 1838:growth factors 1829: 1826: 1824: 1821: 1793:ligand-binding 1784: 1781: 1780: 1779: 1775: 1771: 1765: 1762: 1740: 1737: 1729:flow cytometry 1698: 1695: 1677: 1674: 1673: 1672: 1662: 1655: 1609:DNA polymerase 1557: 1554: 1543: 1542: 1531: 1516: 1501:nitrocellulose 1468: 1465: 1443: 1440: 1439: 1438: 1435: 1419: 1412: 1410:polyacrylamide 1373: 1370: 1332: 1329: 1327: 1324: 1303:refractometers 1254: 1251: 1227:conductometric 1211:potentiometric 1205:detection and 1154: 1151: 1138:damped mediums 1129:piezo-resistor 1108: 1105: 1095:interactions, 1091:interactions, 1069:Main article: 1066: 1063: 1053: 1050: 1022: 1019: 1013: 1010: 1001: 998: 994:carbon dioxide 990:Thermoelectric 977: 974: 948: 945: 939: 936: 928:electrowetting 920:micropatterned 912: 911: 901: 890: 879: 872:micromechanics 864: 860: 857:concentrations 825:Main article: 822: 819: 770:electric field 754:electric field 730:Main article: 727: 724: 710:paper include 669:, and natural 646: 643: 621:delivery, and 548:glass surface. 527: 524: 498:hydrophobicity 482:ion-irradiated 417: 414: 368:fusion bonding 364:anodic bonding 351: 348: 346: 343: 341: 338: 314: 313: 303: 296: 290: 245:equipment for 211:DNA sequencing 195:drug discovery 179:pregnancy test 146: 143: 9: 6: 4: 3: 2: 7017: 7006: 7003: 7001: 6998: 6996: 6995:Microfluidics 6993: 6991: 6988: 6987: 6985: 6966: 6963: 6961: 6958: 6956: 6953: 6951: 6948: 6946: 6943: 6941: 6938: 6936: 6933: 6932: 6930: 6926: 6920: 6917: 6915: 6912: 6910: 6907: 6905: 6902: 6900: 6897: 6895: 6892: 6890: 6887: 6885: 6882: 6881: 6879: 6875: 6872: 6868: 6858: 6855: 6853: 6852:Microfluidics 6850: 6848: 6845: 6843: 6840: 6838: 6835: 6833: 6830: 6828: 6825: 6824: 6822: 6818: 6812: 6809: 6807: 6804: 6803: 6801: 6799: 6795: 6789: 6786: 6784: 6781: 6779: 6776: 6775: 6773: 6771: 6767: 6761: 6758: 6757: 6755: 6753: 6749: 6746: 6742: 6736: 6733: 6731: 6728: 6726: 6723: 6722: 6720: 6716: 6710: 6707: 6705: 6702: 6700: 6697: 6696: 6693: 6689: 6682: 6677: 6675: 6670: 6668: 6663: 6662: 6659: 6649: 6645: 6641: 6637: 6633: 6629: 6625: 6621: 6614: 6606: 6602: 6598: 6594: 6590: 6586: 6582: 6578: 6577:Lab on a Chip 6571: 6563: 6559: 6555: 6551: 6547: 6543: 6539: 6535: 6531: 6527: 6520: 6518: 6516: 6514: 6512: 6510: 6508: 6506: 6504: 6495: 6491: 6487: 6483: 6479: 6475: 6470: 6465: 6461: 6457: 6450: 6448: 6446: 6437: 6433: 6428: 6423: 6419: 6415: 6411: 6404: 6396: 6392: 6388: 6384: 6380: 6376: 6372: 6368: 6364: 6360: 6356: 6352: 6348: 6340: 6332: 6328: 6323: 6318: 6314: 6310: 6306: 6302: 6298: 6294: 6290: 6283: 6275: 6271: 6267: 6263: 6258: 6257:2027.42/47852 6253: 6249: 6245: 6241: 6237: 6230: 6222: 6218: 6214: 6210: 6206: 6202: 6198: 6194: 6190: 6186: 6182: 6178: 6170: 6162: 6158: 6154: 6150: 6146: 6142: 6138: 6134: 6130: 6126: 6119: 6111: 6107: 6103: 6099: 6095: 6091: 6087: 6083: 6082:Lab on a Chip 6075: 6067: 6063: 6059: 6055: 6051: 6047: 6043: 6039: 6032: 6024: 6020: 6015: 6010: 6007:(9): 1944–7. 6006: 6002: 5998: 5991: 5983: 5979: 5975: 5971: 5966: 5961: 5957: 5953: 5949: 5945: 5944:Lab on a Chip 5938: 5930: 5926: 5922: 5918: 5914: 5910: 5906: 5902: 5901:Lab on a Chip 5894: 5886: 5882: 5878: 5874: 5870: 5866: 5862: 5858: 5854: 5847: 5839: 5835: 5830: 5825: 5821: 5817: 5813: 5809: 5805: 5801: 5797: 5790: 5782: 5778: 5774: 5770: 5766: 5762: 5758: 5754: 5750: 5746: 5739: 5732: 5724: 5720: 5716: 5712: 5708: 5704: 5700: 5696: 5695:Lab on a Chip 5689: 5681: 5677: 5673: 5669: 5664: 5659: 5655: 5651: 5647: 5643: 5636: 5628: 5624: 5620: 5616: 5612: 5608: 5604: 5600: 5593: 5585: 5581: 5576: 5571: 5567: 5563: 5559: 5555: 5551: 5547: 5543: 5536: 5528: 5524: 5520: 5516: 5511: 5506: 5502: 5498: 5494: 5487: 5479: 5475: 5471: 5467: 5462: 5457: 5453: 5449: 5445: 5441: 5440:Lab on a Chip 5433: 5425: 5421: 5417: 5413: 5409: 5405: 5401: 5397: 5390: 5388: 5386: 5384: 5382: 5380: 5378: 5376: 5374: 5372: 5370: 5368: 5366: 5364: 5362: 5360: 5358: 5349: 5345: 5340: 5335: 5331: 5327: 5322: 5317: 5313: 5309: 5306:(8): e42804. 5305: 5301: 5297: 5290: 5282: 5278: 5273: 5268: 5264: 5260: 5256: 5252: 5248: 5244: 5240: 5236: 5232: 5225: 5217: 5213: 5209: 5205: 5201: 5197: 5193: 5189: 5182: 5174: 5170: 5165: 5160: 5156: 5152: 5148: 5144: 5137: 5129: 5125: 5121: 5117: 5113: 5109: 5106:(1): 149–54. 5105: 5101: 5100:Lab on a Chip 5094: 5086: 5082: 5078: 5074: 5070: 5066: 5062: 5058: 5051: 5044: 5033: 5029: 5023: 5015: 5008: 5006: 5004: 4995: 4991: 4987: 4983: 4979: 4975: 4974:Lab on a Chip 4968: 4966: 4957: 4953: 4949: 4945: 4941: 4937: 4933: 4929: 4922: 4914: 4910: 4905: 4900: 4896: 4892: 4888: 4884: 4880: 4873: 4871: 4869: 4867: 4858: 4854: 4850: 4846: 4842: 4838: 4834: 4830: 4823: 4816: 4814: 4812: 4810: 4808: 4806: 4804: 4802: 4793: 4789: 4784: 4779: 4775: 4771: 4766: 4761: 4757: 4753: 4750:(3): e33176. 4749: 4745: 4741: 4737: 4730: 4722: 4718: 4714: 4710: 4706: 4700: 4696: 4692: 4688: 4681: 4679: 4677: 4668: 4664: 4659: 4654: 4650: 4646: 4642: 4638: 4634: 4630: 4626: 4619: 4617: 4615: 4613: 4611: 4609: 4600: 4596: 4592: 4588: 4584: 4580: 4576: 4572: 4565: 4563: 4561: 4559: 4550: 4544: 4540: 4536: 4532: 4525: 4517: 4513: 4508: 4503: 4500:(3): 615–22. 4499: 4495: 4488: 4481: 4479: 4477: 4475: 4473: 4471: 4469: 4460: 4456: 4452: 4448: 4444: 4440: 4436: 4432: 4425: 4423: 4421: 4412: 4408: 4403: 4398: 4394: 4390: 4386: 4382: 4378: 4374: 4370: 4363: 4361: 4351: 4346: 4342: 4338: 4334: 4330: 4326: 4322: 4315: 4313: 4304: 4300: 4296: 4292: 4288: 4284: 4280: 4276: 4272: 4268: 4261: 4254: 4246: 4240: 4236: 4232: 4228: 4221: 4219: 4217: 4215: 4206: 4202: 4198: 4194: 4190: 4186: 4179: 4177: 4168: 4164: 4159: 4154: 4149: 4144: 4140: 4136: 4132: 4125: 4123: 4121: 4119: 4110: 4106: 4101: 4096: 4092: 4088: 4084: 4080: 4079:Lab on a Chip 4076: 4069: 4067: 4065: 4056: 4052: 4048: 4044: 4040: 4036: 4032: 4028: 4024: 4020: 4013: 4011: 4002: 3998: 3993: 3988: 3984: 3980: 3976: 3972: 3968: 3964: 3960: 3953: 3951: 3949: 3940: 3936: 3931: 3926: 3922: 3918: 3913: 3908: 3904: 3900: 3896: 3892: 3888: 3881: 3873: 3869: 3864: 3859: 3855: 3851: 3846: 3841: 3837: 3833: 3829: 3825: 3821: 3814: 3806: 3802: 3798: 3794: 3790: 3786: 3779: 3771: 3767: 3762: 3757: 3753: 3749: 3745: 3741: 3740:Lab on a Chip 3737: 3730: 3722: 3718: 3714: 3710: 3706: 3702: 3695: 3693: 3684: 3680: 3676: 3672: 3668: 3664: 3660: 3656: 3649: 3647: 3638: 3634: 3630: 3626: 3622: 3618: 3614: 3610: 3606: 3602: 3598: 3594: 3587: 3579: 3575: 3571: 3567: 3563: 3559: 3555: 3551: 3544: 3542: 3535: 3528: 3526: 3517: 3505: 3497: 3493: 3488: 3483: 3479: 3475: 3470: 3465: 3461: 3457: 3452: 3447: 3444:(5): e37548. 3443: 3439: 3435: 3428: 3426: 3417: 3413: 3409: 3405: 3401: 3397: 3389: 3381: 3377: 3373: 3369: 3365: 3361: 3357: 3353: 3349: 3345: 3338: 3336: 3334: 3332: 3330: 3328: 3326: 3324: 3322: 3320: 3318: 3316: 3314: 3312: 3310: 3308: 3306: 3304: 3302: 3300: 3298: 3296: 3294: 3292: 3290: 3281: 3275: 3271: 3267: 3263: 3256: 3254: 3252: 3250: 3248: 3246: 3244: 3242: 3233: 3229: 3224: 3219: 3215: 3211: 3206: 3201: 3197: 3193: 3189: 3185: 3181: 3174: 3172: 3163: 3159: 3155: 3151: 3147: 3143: 3139: 3135: 3131: 3127: 3120: 3112: 3108: 3104: 3100: 3096: 3092: 3088: 3084: 3080: 3076: 3072: 3065: 3057: 3053: 3049: 3045: 3041: 3037: 3033: 3029: 3025: 3021: 3014: 3012: 3010: 3008: 3006: 2997: 2993: 2989: 2985: 2981: 2977: 2973: 2969: 2965: 2961: 2957: 2953: 2946: 2938: 2934: 2930: 2926: 2922: 2918: 2911: 2903: 2897: 2893: 2886: 2884: 2882: 2880: 2878: 2876: 2874: 2872: 2870: 2868: 2866: 2864: 2862: 2860: 2858: 2856: 2854: 2852: 2850: 2848: 2846: 2844: 2842: 2840: 2838: 2836: 2834: 2832: 2830: 2828: 2826: 2824: 2822: 2820: 2818: 2816: 2814: 2812: 2810: 2808: 2806: 2804: 2802: 2800: 2798: 2796: 2794: 2792: 2790: 2788: 2786: 2784: 2782: 2780: 2778: 2776: 2774: 2772: 2770: 2768: 2766: 2764: 2762: 2760: 2758: 2756: 2754: 2752: 2750: 2748: 2746: 2744: 2742: 2740: 2738: 2736: 2734: 2732: 2730: 2728: 2726: 2717: 2715:0-8194-5977-1 2711: 2707: 2700: 2698: 2696: 2687: 2683: 2679: 2675: 2671: 2667: 2663: 2659: 2658:Lab on a Chip 2655: 2653: 2644: 2640: 2633: 2630: 2626: 2622: 2618: 2614: 2610: 2606: 2601: 2600:piezoelectric 2597: 2593: 2589: 2585: 2584:gene delivery 2581: 2577: 2572: 2568: 2567:drug delivery 2564: 2561:systems, and 2560: 2552: 2548: 2544: 2538:Drug delivery 2535: 2533: 2529: 2526:, pressures, 2525: 2521: 2517: 2513: 2509: 2505: 2501: 2497: 2493: 2488: 2485:Bio-MEMS for 2480: 2477:sensors, and 2476: 2472: 2467: 2458: 2455: 2451: 2447: 2443: 2439: 2435: 2431: 2426: 2422: 2418: 2417:encapsulation 2414: 2410: 2406: 2402: 2398: 2394: 2390: 2389:bioelectrical 2386: 2382: 2367: 2365: 2361: 2357: 2353: 2349: 2345: 2340: 2336: 2335:Microfluidics 2332: 2328: 2324: 2320: 2316: 2312: 2303: 2301: 2297: 2293: 2289: 2288:embryoid body 2284: 2281: 2278:are a common 2277: 2269: 2260: 2258: 2253: 2249: 2245: 2241: 2237: 2233: 2224: 2222: 2218: 2214: 2210: 2206: 2202: 2199: 2195: 2191: 2187: 2183: 2179: 2175: 2171: 2167: 2163: 2159: 2155: 2151: 2147: 2143: 2139: 2129: 2127: 2126:cell adhesion 2124: 2120: 2116: 2112: 2108: 2104: 2103:organogenesis 2100: 2099:embryogenesis 2096: 2086: 2084: 2083:microchannels 2080: 2076: 2072: 2068: 2064: 2060: 2059:dose-response 2049: 2047: 2043: 2039: 2035: 2030: 2029:embryoid body 2026: 2022: 2018: 2014: 2010: 2002: 1997: 1988: 1986: 1982: 1978: 1974: 1970: 1966: 1962: 1958: 1954: 1950: 1946: 1942: 1938: 1937: 1932: 1928: 1924: 1920: 1916: 1913:which can be 1912: 1908: 1903: 1901: 1896: 1892: 1888: 1884: 1880: 1876: 1872: 1868: 1864: 1860: 1856: 1852: 1847: 1844:, genes, and 1843: 1842:neuropeptides 1839: 1835: 1832:Conventional 1820: 1818: 1814: 1810: 1805: 1801: 1797: 1794: 1790: 1776: 1772: 1768: 1767: 1761: 1759: 1755: 1750: 1746: 1736: 1734: 1733:microfluidics 1730: 1726: 1721: 1716: 1712: 1708: 1704: 1694: 1687: 1682: 1670: 1666: 1663: 1660: 1656: 1653: 1649: 1646:channels for 1645: 1641: 1637: 1636: 1635: 1633: 1629: 1624: 1619: 1615: 1614:heat transfer 1610: 1606: 1602: 1598: 1597:amplification 1594: 1590: 1582: 1578: 1574: 1570: 1567: 1562: 1553: 1551: 1550: 1540: 1536: 1532: 1529: 1525: 1521: 1517: 1514: 1510: 1506: 1505: 1504: 1502: 1498: 1494: 1490: 1486: 1482: 1478: 1474: 1464: 1461: 1456: 1448: 1436: 1432: 1428: 1424: 1420: 1417: 1413: 1411: 1407: 1406: 1405: 1403: 1399: 1395: 1391: 1387: 1383: 1379: 1369: 1367: 1363: 1358: 1354: 1350: 1346: 1343:The goals of 1337: 1323: 1321: 1317: 1313: 1308: 1304: 1300: 1296: 1292: 1288: 1284: 1280: 1276: 1272: 1268: 1264: 1260: 1250: 1248: 1244: 1243:nucleic acids 1240: 1235: 1232:, changes in 1231: 1228: 1224: 1220: 1216: 1212: 1208: 1204: 1200: 1196: 1192: 1188: 1184: 1180: 1176: 1172: 1168: 1164: 1160: 1150: 1148: 1143: 1139: 1134: 1130: 1126: 1122: 1118: 1114: 1104: 1102: 1098: 1094: 1090: 1086: 1082: 1078: 1072: 1062: 1059: 1049: 1047: 1043: 1039: 1035: 1027: 1018: 1009: 1007: 997: 995: 991: 982: 973: 971: 967: 963: 962:Stephen Quake 953: 944: 935: 933: 929: 925: 921: 917: 910: 906: 902: 899: 895: 891: 889: 886:, as well as 885: 880: 877: 873: 869: 865: 861: 858: 854: 850: 849: 845: 841: 836: 832: 828: 827:Microfluidics 821:Microfluidics 818: 815: 811: 807: 803: 799: 795: 791: 787: 783: 779: 775: 771: 767: 763: 755: 751: 747: 743: 738: 733: 723: 721: 717: 716:laser cutting 713: 709: 705: 701: 697: 693: 689: 685: 681: 676: 675:microfluidics 672: 668: 664: 660: 659:microfluidics 656: 652: 642: 640: 636: 632: 628: 624: 620: 616: 612: 608: 604: 600: 596: 592: 588: 584: 580: 576: 572: 568: 564: 556: 552: 547: 543: 539: 536: 532: 523: 521: 517: 513: 509: 505: 504: 499: 495: 491: 487: 483: 479: 475: 471: 467: 463: 459: 455: 451: 447: 443: 439: 435: 431: 427: 423: 413: 411: 407: 406: 401: 397: 393: 389: 385: 381: 377: 373: 372:flow channels 369: 365: 361: 357: 337: 335: 331: 330:self-assembly 327: 323: 319: 312: 311:microchannels 308: 307:laminar flows 304: 301: 297: 295: 294:drug delivery 291: 288: 284: 283: 282: 280: 276: 272: 268: 264: 260: 256: 252: 248: 244: 240: 236: 232: 228: 224: 220: 216: 212: 208: 204: 200: 196: 192: 188: 184: 180: 176: 172: 168: 164: 156: 151: 139: 134: 130: 128: 124: 120: 116: 112: 108: 104: 100: 96: 92: 88: 84: 80: 76: 72: 68: 64: 60: 56: 55:lab-on-a-chip 52: 48: 44: 40: 39: 35: 30: 23: 18: 6914:Wire bonding 6846: 6744:Applications 6735:Microchannel 6623: 6619: 6613: 6580: 6576: 6570: 6532:(1): 31–39. 6529: 6525: 6462:(1): 43–55. 6459: 6455: 6417: 6413: 6403: 6354: 6350: 6339: 6296: 6292: 6282: 6239: 6235: 6229: 6180: 6176: 6169: 6128: 6124: 6118: 6085: 6081: 6074: 6041: 6037: 6031: 6004: 6000: 5990: 5947: 5943: 5937: 5907:(6): 770–6. 5904: 5900: 5893: 5860: 5856: 5853:Lee, Luke P. 5846: 5803: 5800:Biomaterials 5799: 5789: 5748: 5744: 5731: 5701:(1): 111–8. 5698: 5694: 5688: 5653: 5649: 5635: 5602: 5598: 5592: 5549: 5545: 5535: 5500: 5496: 5486: 5446:(4): 401–6. 5443: 5439: 5432: 5399: 5395: 5303: 5299: 5289: 5238: 5234: 5224: 5191: 5187: 5181: 5146: 5136: 5103: 5099: 5093: 5060: 5056: 5050: 5041: 5035:. 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