ISSN:1473-0197    

DOI:10.1039/b500478k

出版商:RSC    

年代:2005

数据来源: RSC

ISSN:1473-0197    

DOI:10.1039/b400381k

出版商:RSC    

年代:2004

数据来源: RSC

摘要:

Education/EmploymentM.Sc. Applied Physics, University of TwentePh.D. Technical Sciences, University of TwenteScientist at CSEM, Chemical Sensors DepartmentSenior Scientist at IMTProgram Director μTAS at MESA, University of TwentePart-time appointment as Full Professor ‘Microfluidics’Program Director MiCS at MESA+, University of TwenteSimon Stevin Award, STW2002 – the present: Full Professor at ‘BIOS’-chair, The Lab-on-a-Chip Group

ISSN:1473-0197    

DOI:10.1039/b400106k

出版商:RSC    

年代:2004

数据来源: RSC

摘要:

IntroductionMicrofluidic chip-based platforms have become increasingly popular in recent years for applications such as separation and detection,1–5PCR and/or DNA analysis,6–11and cell manipulation12–14owing to the speed of chip-based processes and the potential for very-large-scale integration. Using microfluidic devices for applications involving biological cells has been motivated by the potential for integrating manipulation and analysis steps, as well as increased sampling throughput and efficiency. Cell adhesion in chips, which results from hydrophobic and electrostatic interactions between cells and the extracellular silica substrate, is a major stumbling block to single- and multiple-cell analyses unless cells are chosen specifically to avoid adhesion. Techniques that reduce cell adhesion must be compatible with various buffers and techniques used for cell analysis (e.g., electrophoresis, and absorbance/LIF detection).

ISSN:1473-0197    

DOI:10.1039/b210621n

出版商:RSC    

年代:2002

数据来源: RSC

摘要:

BackgroundGeSiM1mbH (short for Gesellschaft für Silizium-Mikrosysteme mbH,i.e., ‘Silicon Microsystems Company Ltd.’) has its origins in research projects performed at the Forschungszentrum Rossendorf,2a major research facility in the former East Germany where materials research, the basis of GeSiM, has become one of the focal points after the German reunification. GeSiM’s aim is to develop integrated microfluidic systems to aid the miniaturisation of biotechnological processes. GeSiM is a world leader in non-contact subnanolitre dosage and microarraying and maintains a cleanroom facility in which microsystems can be built according to customers’ requests. As a small company, GeSiM cannot offer the latest, fanciest, and most expensive technology, but it does offer a cost-effective and fast one-stop service which includes processes as diverse as the development and production of microfluidic devices, chip packaging, and the manufacturing of entire instruments.The past few years there has been much hype around lab-on-a-chip technologies; many people have entered the field and maybe more have been writing about it. But with the possible exception of microarrays, the market has reacted indifferently to these developments. This attitude is about to change, because so many achievements have been made. What then are the advantages of ‘micro’ in biotechnology? The biggest point is parallel sample processing, which by definition enables high throughput to screen either nucleic acids, proteins, whole cells, or chemicals, thus saving an enormous amount of time while keeping the workforce away from tedious repetitive tasks. The second point is the decrease of sample volume and thus a dramatic reduction of costs (of expensive enzymes, nucleic acids,etc.). GeSiM, as a company not dependent on venture capital, have taken a pragmatic, evolutionary approach to microsystems technology in the biotech in that they introduce novelties one at a time and test their marketability. This, however, requires customers who know what lab-on-a-chip devices they need.

ISSN:1473-0197    

DOI:10.1039/b212706g

出版商:RSC    

年代:2003

数据来源: RSC

摘要:

IntroductionThe development of multifunctional, high throughput lab-on-a-chip devices depends heavily on the ability to measure flow rate and perform quantitative analysis of fluids in minute volumes. Traditionally, there have been many MEMS-based (MEMS = microelectromechanical system) flow sensors for gaseous flows.1In recent times, there has been some advancement in measuring micro-flows of liquids. Examples of sensing principles explored in the measurement of microfluidic flow are heat transfer detection,2–4molecular sensing,5atomic emission detection,6streaming potential measurements,7electrical impedance tomography,8ion-selective field-effect transitors9and periodic flapping motion detection.10Flow sensors form the integral part of micrototal analysis systems11with multisensors. Conversely, a measure of electric current is used for pumping a measurable flow rate of fluids in electro-osmotic flow (EOF).12Flow sensors based on sensing the temperature difference between two points in the microchannel2–4can sense very low flows. However, such flow sensors require a complicated design and the integration of the heater, temperature sensors and membrane shielding is difficult to implement. Moreover, the sensitivity and accuracy of the flow sensors depend on the environment associated in the heat transfer. Most other methods are not capable of measuring very low flow rates. We consider flow sensing by directly measuring the electrical admittance of the fluid using two surface electrodes.In electrolytes flowing in a microchannel under laminar flow conditions, a parabolic velocity profile exists and so the ions in the middle of the channels travel faster than those near the walls. This results in the redistribution of ions within the electric double layer (EDL) formed in the channel.13The ac voltage across the channel electrodes (Fig. 3) drives the ions back and forth across the electrodes. The ionic redistribution develops electrokinetic effects and contributes to change in electric admittance. Thus the flow of fluid is very sensitive to the admittance across microelectrodes14,15in the flow channels, and measuring the increase in admittance precisely accounts for the flow rate. Our flow sensor operating with optimized electric parameters can be efficient and accurate for precise values of flows. This method is relatively simple and suitable for most of the chemical and biochemical microfluidic applications since most of the reagents used are electrolytes. In this paper, we present such a flow sensor based on the measurement of electrical admittance.PrincipleIn hydrodynamic conditions, forced convection dominates the transport of ions to the electrodes within the flow channels. When the width of the microfluidic channel is very small compared to the length of the channel, the lateral diffusion of the ions is significant under laminar flow. Under an ac electrical signal applied across the channel, the equivalent circuit16of the microsystem is shown inFig. 1. The electrical double layer17formed across the channel is formed from two capacitances namely diffuse layer capacitance (Cs) and the outer Helmholtz plane capacitance (Ce). The former is due to ion excess or depletion in the channel, and the latter is due to the free electrons at the electrodes and is independent of the electrolyte concentration. The smaller of these capacitances dominates the admittance since these two capacitances are in series. The frequency of the applied ac voltage, flow rate and conductivity of the fluid are the factors affecting the admittance of the fluidic system and our flow sensing principle is based on the optimization of these parameters.The equivalent circuit for the channel and electrodes flow sensor cell. The solution in the channel offers a parallel resistive (Rs) and capacitive (Cs) impedance while the electrodes by themselves offer serial capacitive (Ce) impedance with the solution.For an electrochemical oxidation of a species A to A+in a microchannel, the convective–diffusive equation for mass transport under steady state conditions is given byeqn. (1):1where [A] is the concentration of the species,DAis the diffusion coefficient andvxis the velocity in the direction of flow. The first term is the lateral diffusion in the microchannel and the second term is the transport along the length of the channel. Under steady state flow conditions the boundary condition is given byeqn. (2). The solution of this equation predicts the mass transport limited current (iL)18as a function of flow rate,Qas given byeqn. (3):23wherenis the number of electrons transferred,F, the Faraday constant,xeis the electrode length,h, the cell half-height,d, the width of the cell andw, the electrode width. It is to be noted that the current due to flow of electrolyte is directly proportional to the cube root of volume flow rate of the fluid. The ac voltage signal is considered rather than dc voltage since the application of an ac voltage in the flow sensor does not promote any electrode reaction. Optimization of the electrical parameters like voltage and frequency of the ac signal are considered as an operating condition for measuring low flow rates. This optimizes the distance of movement of ions and their relaxation behavior across the channel electrodes so that the current admittance suffered is maximum.

ISSN:1473-0197    

DOI:10.1039/b310282c

出版商:RSC    

年代:2003

数据来源: RSC

摘要:

Andrew J. deMellois a Senior Lecturer at Imperial College London. He obtained a First Class honours degree in Chemistry from Imperial College in 1991, and subsequently completed a doctorate in the field of molecular photophysics. He then moved to the University of California, Berkeley where he held a post-doctoral research fellowship in the Department of Chemistry. Between 1996 and 1997, Dr deMello held a lectureship in Physical Chemistry at the University of East Anglia.Dr deMello′s current research programmes are centred on the areas of miniaturised chemical analysis systems and ultra-high sensitivity detection. Generally, studies focus on performing chemistry in picoliter volumes, high-efficiency manipulation of small liquid samples and investigating novel phenomena on the microscale. In particular he has an established track record in the development of microdevices for DNA analysis, microfluidic reactors for small molecule and nanomaterial synthesis, novel chip-based detection protocols and evanescent wave and single molecule spectroscopies. He was a member of the Genome Instrumentation Panel, DOE, USA (1998), and is currently a member of the Detection and Decontamination of Chemical and Biological Weapons Working Group of The Royal Society.Dr. deMello has co-authored one book and in excess of 60 scientific publications in scientific journals. Since 1997, he has given over 70 oral presentations on various aspects of his research on microfluidic systems. Dr deMello was awarded the 2002 SAC Silver Medal by the Royal Society of Chemistry for his contributions to the Analytical Sciences.

ISSN:1473-0197    

DOI:10.1039/b315960b

出版商:RSC    

年代:2004

数据来源: RSC

摘要:

Liquid TeflonSoft lithography has become highly popular over the past few years, offering a rapid, flexible and low-cost route to the creation of micron-sized features on planar substrates. Soft lithographic methods describe the moulding of elastomeric polymers using master templates. Elastomeric siloxane polymers such as PDMS are easily moulded, optically transparent (well into the UV), durable, cheap, non-toxic and stable over wide temperature ranges. Such materials can be cast against a positive relief template to form microfluidic structures with high aspect ratios by simply pouring a mixture of the elastomer precursor and a curing agent over a template. After curing the structured polymer is peeled away from the template and an enclosed fluidic structure created by contacting the elastomer with a planar surface. Although PDMS exhibits useful chemical properties such as significant gas permeability, biocompatibility and a low surface energy, it is not robust to a wide range of solvents and reagents. For example, PDMS has limited compatibility with many organic solvents and can appreciably swell upon contact with solvents such as hexane, dichloromethane, toluene and acetonitrile.To address this limitation Joseph DeSimone and co-workers at the University of North Carolina at Chapel Hill, North Carolina State University and Caltech show that perfluoropolyethers (PFPEs) are excellent elastomeric materials suitable for microfluidic applications. As with PDMS, PFPEs exhibit low surface energies, low Young's moduli, high gas permeabilities, but also possess chemical resistivities similar to that of Teflon. The authors fabricate devices by partially photocuring PFPE layers to provide rigidity without compromising feature sizes, and fully curing after repositioning to enable adhesion and channel creation. Fully cured PDMS and PFPE materials were shown to exhibit similar elastic behaviour at room temperature and also have similar tensile moduli. Nevertheless, PFPE devices were shown to be resistant to toluene and dichloromethane, with negligible swelling. PFPEs will undoubtedly prove useful in creating elastomeric structures for use in a variety of chemical applications inaccessible to conventional silicone materials.Journal of the American Chemical Society, 2004,126, 2322–2323.

ISSN:1473-0197    

DOI:10.1039/b403700f

出版商:RSC    

年代:2004

数据来源: RSC

摘要:

Professor David BeebeProfessor Albert FolchFrom the beginning of MicroElectro Mechanical Systems, biological applications for micro devices have been envisioned. Early micromotors prompted thoughts of micro "roto rooters" that might someday clean plaque from arteries. While this vision has not been fulfilled, several successful commercial applications of MEMS have appeared. With the emergence of microfluidics and soft lithography techniques, the hopes for successful biological applications were again raised. However, only recently has the field matured to where microfluidic systems for biology have gone beyond simply replicating methods and techniques performed using more traditional means. As highlighted in this special issue, the development of Lab on a Chip devices for cell biology is rapidly moving from demonstration to utility. One of the key shifts has been to a more intelligent use of micro scale phenomena and systems to either improve functionality or more importantly, to perform functions in beneficial ways not possible before. There are numerous biomedical applications that benefit from miniaturization. The materials and fabrication methods used are as varied as the application to which they are best suited, but the common theme is one of new or enhanced performance.While cell culture has become an essential tool in cell and molecular biology and in biotechnology, it is now falling behind in the pace of progress brought by genome sequencing, imaging probes, and high-throughput testing of biochemicals. For over a century, cell culture technology has essentially consisted of the immersion of a large population of cells in a homogeneous fluid medium. This requires large numbers of cell culture surfaces, bulky incubators, large fluid volumes, and expensive human labor and/or equipment. Moreover, cells respond to local concentrations of a variety of molecules which may be dissolved in the extracellular medium (e.g., enzymes, nutrients, small ions), present on neighboring scaffolds (e.g., extracellular matrix proteins) or on the surface of adjacent cells (e.g., membrane receptors). Microfabrication technology has an inherent potential for providing the next generation of cell culture and cell analysis tools where large numbers of single cells or small cell populations can be probed inexpensively, at high throughput, and in a cellular microenvironment of increased physiological relevance with respect to present cell culture methods.The 16 papers gathered for this special issue span a wide range of topic areas across "the science and applications of cell biology in microsystems." Papers from Schuler1and Williams2describe systems designed to provide insights into very basic biological questions such as the mechanisms responsible for the development of tight intercellular junctions in the blood–brain barrier and thermal control of dorsal root ganglion neurons respectively. Important considerations when designing microsystems for cell culture were recently discussed in LOC.3Four papers describe systems that address various aspects of culturing cells in Lab on a Chip. Lee4describes a system for high throughput cell culture, while Kennedy5demonstrates the ability to monitor insulin secretion using electrophoretic-based immunoassays on continuously perfused cells. Jeon6and Folch7describe methods and systems that allow for patterning cells within microchannels and for their long term study (6 days and > 2 weeks, respectively) and Bhatia describes patterning in a 3D hydrogel matrix.8Systems that allow enhanced separation or sorting functionality are described by Liepmann9and Toner,10while Jensen11and Lee12utilize electroporation for cell lysis and for increasing cell membrane permeability. Van den Berg describes a microfluidic chip for cell trapping enabling imaging of cell status after exposure to fluorophores indicating different states of cell death.13One of the earliest examples of microfluidics and cell biology is in the field of embryology. This tradition continues here with three papers that describe advances in this area. Park14describes a system to transport, isolate, orient and immobilize embyros. Chemical and mechanical manipulation of embryos is described in two papers by Beebe15,16that demonstrate enhanced functionality over traditional methods. Finally, Laurell17describes a method for the efficient separation of lipid particles from red blood cells in a system that should have important clinical applications. In summary, this special issue, while far from exhaustive, presents a selection of the state-of-the-art in the science and application of cell biology in microsystems. As these papers make clear, the field is rapidly moving from exploratory demonstrations to sophisticated and targeted applications where the unique properties of microsystems can be leveraged to provide new or enhanced functionality.Professor David BeebeDept. of Biomedical EngineeringUniversity of Wisconsin2142 Engineering Centers Bldg1550 Engineering DriveMadison WI 53706USAProfessor Albert FolchBioengineering Dept.University of WashingtonCampus Box 352255SeattleWA 98195USA

ISSN:1473-0197    

DOI:10.1039/b418165b

出版商:RSC    

年代:2004

数据来源: RSC

摘要:

How pathogen bacteria colonise the intestineEpithelial cells in the gastrointestinal tract of humans co-exist with non-pathogenic, so called commensal bacterial cells. Indeed, the interactions between the bacteria and the intestine host cells are important for normal intestine functioning. Infections by pathogenic bacterial cells can severely disturb the balance between host cells and commensal bacteria. Interestingly, few pathogen bacterial cells are often sufficient to out-compete huge numbers of non-pathogen bacterial cells, and manage to pass the commensal layer and infect the intestine epithelial cells. From former investigations on intestine infections it became evident that some signalling molecules produced by the commensal bacteria in high concentration play a significant role on pathogen infection. Arul Jayaraman and co-workers from Texas A&M University (College Station, TX, USA) could now investigate in more detail the interactions of host cells and pathogen bacteria and influences by signalling molecules by means of a microfluidic device.1The device is designed to form localised cultures of epithelial cells (HeLa cells) and commensal bacteria. This is achieved by integration of a pneumatically controlled trap for the bacterial cells into a microchannel that contains the epithelial cells. After introduction of the cells in their respective compartment, epithelial cells reached confluence after 48 h, while the bacterial cells formed a biofilm during the same time. Subsequent introduction of pathogen bacterial cells (enterohemorrhagic E.coli, EHEC) into the bacteria cell trap resulted in uniform distribution of the pathogen cells within the commensal cell population. Next, 6 hours after introduction of EHEC cells, the cell trap is opened to allow the migration of pathogen cells into the epithelial cell layer, and the infection of the epithelial cells around the cell traps is determined using a live/dead cell assay. This system can be used to study influences of signalling molecules on infection. For this the authors repeated the experiment using a mutant of the commensal bacterial cells that do not produce the signalling molecule indole. After introduction of pathogen cells and opening the trap, it turns out that the number of dead epithelial cells significantly increased,i.e.the infectivity of the pathogen cells doubled. Pre-treatment of the epithelial cells with indole could only partially decrease the infectivity. In other words, high local concentration of the signalling molecules seems to support more efficient infection of epithelial cells than equal distribution of the signalling molecules. The method described in the paper could be extended to investigate the role of other signalling molecules. It might be useful as well for screening probiotic cell strains for modulating pathogen infectivity on the gastrointestinal tract.

ISSN:1473-0197    

DOI:10.1039/b923816f

出版商:RSC    

年代:2009

数据来源: RSC