Forgot your password?
New user?
New Window Opens on the Secret Life of Microbes: Scientists Develop First Microbial Profiles of Ecosystems
CAS announces the release of SciFinder Scholar for Mac OS X
Press Releases
Press Releases
| Check out our New Publishers' Select for Free Articles |
Analytical and Bioanalytical Chemistry (v.371, #2)
No Title by Hussein M. Sorouraddin; Akihide Hibara; Takehiko Kitamori (pp. 91-96).
A new method for determination for catecholamines (CA) utilizing microchip technology and a thermal lens microscope has been developed. Microchannels with a 250 μm×100 μm cross section were used for mixing, reaction, and detection. Epinephrine (EP), nor-epinephrine (NE), dopamine (DA), and L-dopa (LD) were determined by using coloring oxidization to aminochromes by sodium metaperiodate. A thermal lens microscope (TLM) was used for detection of the product. The sensitivity of the system was comparable for the four CA and required only 15 s for mixing of sample and reagent. The calibration lines indicated excellent linearity for concentrations of 5–20 μg mL–1. The relative standard deviations for 10 μg mL–1 solution were 1.08, 2.18, 2.2, and 2.5% for EP, NE, DA, and LD, respectively. CA in pharmaceutical injections were also determined by use of the system and the results correlated very well with nominal values. Results obtained by use of the integrated system suggested there was a sufficient possibility to realize high-throughput medical diagnosis systems.
No Title by Bernhard H. Weigl; Ron L. Bardell; Natasa Kesler; Christopher J. Morris (pp. 97-105).
Microfluidic structures for the generation of laminar fluid diffusion interfaces (LFDIs) for sample preparation and analysis are discussed. Experimental data and the results of fluid modeling are shown.LFDIs are generated when two or more streams flow in parallel in a single microfluidic structure without any mixing of the fluids other than by diffusion of particles across the diffusion interface. It has been shown that such structures can be used for diffusion-based separation and detection applications. The method has been applied to DNA desalting, the extraction of small proteins from whole blood samples, and the detection of various constituents in whole blood, among other examples.In this paper the design and manufacture of self-contained microfluidic cartridges for the extraction of small molecules from a mixture of small and large molecules by diffusion is demonstrated. The cards are operated without any external instrumentation, and use hydrostatic pressure as the driving force. The performance of the cartridges is illustrated by separating fluorescein from a mixture of fluorescein and dextran of molecular weight 2×106. In a single pass, 98.6% of dextran was retained in the product whereas 43.1% of fluorescein was removed. The method is adjustable for different separation requirements, and computational fluid dynamics (CFD) models are shown that demonstrate the tuning of various microfluidic parameters to optimize separation performance.Other applications of LFDIs for establishment of stable concentration gradients, and the exposure of chemical constituents or biological particles to these concentration gradients are shown qualitatively. Microfluidic chips have been designed for high-throughput screening applications that enable the uniform and controlled exposure of cells to lysing agents, thus enabling the differentiation of cells by their sensitivity to specific agents in an on-chip cytometer coupled directly to the lysing structure.
No Title by Ring-Ling Chien; Wallace J. Parce (pp. 106-111).
A multiport system suitable for pressure control on a lab-on-a-chip microfluidic device is described. An algorithm and a strategy for calculating pressures were developed to control the flow from multiple reservoirs for the microfluidic devices. Dye mixing and enzyme assay titration experiments were performed using pressure-driven flow only. Results show a good linear response over two orders of dynamic range.
No Title by Martin Stelzle; Manfried Dürr; Michael Cieplik; Wilfried Nisch (pp. 112-119).
A micro-chamber for electrophoretic accumulation of charged biomolecules has been designed and evaluated. The system is based on a chip with an array of planar focusing electrodes.Particular attention was devoted to a design which enables penetration of a large sample volume by the electric field of the focusing electrodes. General design principles for a cylindrically symmetrical arrangement of the focusing electrodes were derived.Accumulation of DNA oligomers and streptavidin in aqueous solution was demonstrated. The concentration of biomolecules in the centre of the chip was enhanced by up to a factor of 200.The major fraction of the total charge delivered during electrophoretic accumulation results from Faradaic processes. The maximum charge density deliverable without visible gas formation was determined. By careful control of the voltage and current density applied to the electrodes, evolution of gas bubbles could be avoided for the time required to accumulate analyte molecules in the centre of the micro-chamber.On-chip electrophoretic accumulation of biomolecules can be applied to sample pre-conditioning in lab-on-a-chip devices for analysis of DNA and protein samples.
No Title by Carolin Peter; Markus Meusel; Frank Grawe; Andreas Katerkamp; Karl Cammann; Torsten Börchers (pp. 120-127).
An optical sensor system based on evanescent field excitation of fluorophore-labeled DNA-targets specifically binding to immobilized DNA probes has been developed, thus enabling for real-time analysis of hybridization events. Oligonucleotide probes are directly immobilized on the surface of the disposable sensor chip via biotin/neutravidin linkage and hybridize to complementary Cy5-labeled target DNA in the sample; this is recorded as an increase in the fluorescence signal. Under optimized conditions the hybridization rate was constant and directly proportional to the target concentration. When an 18mer oligonucleotide was used as a probe a linear calibration curve was obtained for a 56mer single-stranded DNA target derived from the neomycin phosphotransferase gene, a selection marker in a variety of genetically modified plants, with an estimated lower limit of detection of 0.21 nmol L–1. No cross-hybridization to a 51mer actin DNA target was observed and even a single-nucleotide mismatch led to a negligible signal. A shutter in the readout device enabled separate detection of targets hybridizing to probes immobilized at the inlet and outlet sides, respectively, of the flow channel. This opens a route toward a real-time DNA array format with analysis times as short as 1–2 min. As a realistic sample a Cy5-labeled 56 bp PCR product was measured after separation of the double-stranded DNA by simple heat denaturation with a detection limit clearly lower than that of traditional gel electrophoresis.
No Title by A. Jung; I. Stemmler; A. Brecht; G. Gauglitz (pp. 128-136).
Sequence-specific detection and quantification of nucleic acids are central steps in many molecular biology procedures which have also been transferred to chip-based procedures. Hybridization-based assays can be used to quantify and discriminate between DNA target sequences down to the level of single base mismatches. Arrays of DNA probes immobilized on a support enable simultaneous testing of multiple sequences of a single sample. DNA arrays can be produced either by in-situ synthesis of oligonucleotides or by immobilization of pre-assembled DNA probes. Covalent and directed immobilization improves the reproducibility and stability of DNA arrays. This is especially interesting with repeated use of transducers or chips.Procedures are described for effective covalent immobilization of pre-assembled amino-linked oligonucleotides, by use of ink-jet techniques, on a modified and heated glass surface, with addressable surface areas ranging from 0.01 mm2 to a few mm2. Almost immediate evaporation of the spotted droplets on the heated surfaces leads to very high surface hybridization capacities. The surfaces are suitable for use with a label-free detection method – reflectometric interference spectroscopy (RIfS). It is shown that hybridization capacity and non-specific interaction at these DNA-surfaces can be characterized by use of RIfS. With a consumption of less than 80 ng·mm–2 oligonucleotide and a specific hybridization capacity of more than 300 fmol mm–2, the activated aminodextran procedure was usually suitable for setting up a DNA array with label-free detection. Non-specific interactions with random oligomers or protein (ovalbumin) were low. Up to 150 repeated regenerations (stripping) of the surfaces by acid treatment and denaturing agents, and 50 days of storage, have been possible without significant loss of hybridization capacity.
No Title by Qiufeng Gao; Yining Shi; Shaorong Liu (pp. 137-145).
Capillary electrophoresis on microfabricated multiple-channel chips has great potential for high-throughput analysis. This review focuses on multiple-channel chips used for high-throughput DNA analysis. It covers progress in the design and fabrication of multiple-channel chips and detection schemes used on these chips. Applications are concentrated on DNA fragment sizing, genotyping, and sequencing.
Microarray sampling-platform fabrication using bubble-jet technology for a biochip system by Leonardo R. Allain; Minoo Askari; David L. Stokes; Tuan Vo-Dinh (pp. 146-150).
The fabrication of microarrays containing PCR-amplified genomic DNA extracts from mice tumors on a Zetaprobe membrane using a modified thermal ink-jet printer is described. A simple and cost-effective procedure for the fabrication of microarrays containing biological samples using a modified bubble-jet printing system is presented. Because of their mass-produced design, ink-jet printers are a much cheaper alternative to conventional spotting techniques. The usefulness of the biochip microarray platform is illustrated by the detection of human fragile histidine triad (FHIT), a tumor suppressor gene. Subcutaneous carcinomas were induced with MKN/FHIT and MKN/E4 cell lines in immunodeficient mice. Several weeks into their development, the tumors from both groups of mice were removed and subjected to DNA extraction by lysis of tissue samples. The extracted DNA samples were amplified by PCR (30 cycles) using the primers corresponding to nucleotides 2 to 18 of the FHIT sequence. The resulting solution was transferred to the individual reservoirs of a three-color cartridge from a conventional thermal ink-jet printer (HP 694C), and arrays were printed on to a Zetaprobe membrane. After spotting, these membranes were used in a hybridization assay, using fluorescent probes, and detected with a biochip.
No Title by Frank F. Bier; Frank Kleinjung (pp. 151-156).
The appeal of microarray technology is the possibility of large-scale parallel determination of a variety of variables simultaneously. Hence, microarray technologies attract the interest of both the scientific and business worlds alike. High-throughput screening has been the major focus of the utilization of microarray technologies in recent years, and has provided the strong driving force for developments in this field. DNA chip and biochip technologies have been developed as a consequence of worldwide activity in genome research. This review focuses on microarray-based analysis and emphasizes some of its principal constraints, especially detection limits.
No Title by Fotini Lamari; Maria Militsopoulou; Xanthee Gioldassi; Nikos K. Karamanos (pp. 157-167).
Proteoglycans are a major family of glycoconjugates which participate in and regulate several cellular events and biological functions. Their glycan chains determine their physicochemical and biological properties. Capillary electrophoresis, because of its high resolving power and sensitivity, has been successfully used for the analysis of carbohydrates. The monosaccharide constituents, the disaccharide sulfation pattern, and the uronic acid distribution within glycan chains of proteoglycans determine their interactions with matrix effectors and are responsible for numerous effects. Determination of the chemical composition and identification of key structural components and domains of glycans are, therefore, essential in understanding the biological functions of proteoglycans. In this report an overview of the capillary electrophoresis methods used to analyze and characterize the structure of the glycan chains of proteoglycans is presented.
No Title by S. Ehala; I. Vassiljeva; R. Kuldvee; R. Vilu; M. Kaljurand (pp. 168-173).
Capillary electrophoresis (CE) can be a valuable tool for on-line monitoring of bioprocesses. Production of organic acids by phosphorus-solubilizing bacteria and fermentation of UHT milk were monitored and controlled by use of a membrane-interfaced dialysis device and a home-made microsampler for a capillary electrophoresis unit. Use of this specially designed sampling device enabled rapid consecutive injections without interruption of the high voltage. No additional sample preparation was required. The time resolution of monitoring in this particular work was approximately 2 h, but could be reduced to 2 min. Analytes were detected at low µg mL–1 levels with a reproducibility of approximately 10%. To demonstrate the potential of CE in processes of biotechnological interest, results from monitoring phosphate solubilization by bacteria were submitted to qualitative and quantitative analysis. Fermentation experiments on UHT milk showed that monitoring of the processes by CE can provide good resolution of complex mixtures, although for more specific, detailed characterization the identification of individual substances is needed.
No Title by Yolanda Fintschenko; Wen-Yee Choi; Sarah M. Ngola; Timothy J. Shepodd (pp. 174-181).
The first rigorous evaluation of a UV-initiated porous polymer monolith (PPM) as a stationary phase for chip electrochromatography (ChEC) is described. All channels in an offset T-injector-design-chip (25-µm deep by 50-µm wide channels) were filled by capillary action with an acrylate-based PPM precursor solution and polymerized in situ using 365 nm light for several minutes. Photodefinability of the monolith cast in the channels during the polymerization process was also demonstrated by masking off the injection arms during photoinitiation. The chromatographic performance of this chip was compared with that of chips completely filled with monolith. The detection window was photodefined after polymerization using the detection laser (257 nm doubled argon ion laser) to depolymerize the detection window. A successful ChEC separation of 10 out of 13 polycyclic aromatic hydrocarbons (PAH) was performed with on-column, off-packing laser-induced fluorescence detection at 257 nm. Van Deemter plots for early-, middle-, and late-eluting compounds showed the minimum plate height to be 5 µm. The average number of theoretical plates per meter for the PAH was 200,000. Several factors contributed to irreproducible results. Oxygen was observed to dynamically quench the fluorescence of the sample over time. Improved sealing of the reservoirs solved this problem. A within-chip variability in the retention time of 2–10% RSD was observed. These results demonstrate the feasibility and reliability of the PPM as a solid reversed-phase for electroosmotic flow-driven chip-based chromatography in microscale total analysis systems.
No Title by Ximo Pous; Mª Ruíz; Yolanda Picó; Guillermina Font (pp. 182-189).
Imidacloprid, metalaxyl, myclobutanil, propham, and thiabendazole have been simultaneously determined in strawberries, oranges, potatoes, pears, and melons by matrix solid-phase dispersion (MSPD) followed by liquid chromatography–atmospheric pressure chemical ionization–mass spectrometry (LC–APCI–MS) in positive-ion mode. The samples were homogenized with C8 bonded silica as MSPD sorbent, placed in a glass column, and eluted with dichloromethane. Chromatographic separation of the compounds was achieved on a reversed-phase LC column using a methanol–ammonium formate (50 mmol L–1) gradient as a mobile phase. Samples were screened by monitoring the protonated molecular ion at m/z 256 for imidacloprid, 280 for metalaxyl, 289 for myclobutanil, and 202 for thiabendazole, and the main fragment at m/z 138 for propham. Positive samples were confirmed by multiple-ion monitoring. The repeatability (<20%) and recovery (>57%) of the method were good, and limits of detection (<0.05 mg kg–1) were adequate.
No Title by Maria Carles; Thomas Lee; Shanti Moganti; Ralf Lenigk; Karl W. Tsim; Nancy Y. Ip; I-Ming Hsing; Nikolaus J. Sucher (pp. 190-194).
Over the last 50 years or so Traditional Chinese medicine (TCM) has been subject to intensive basic and clinical research. Although the effectiveness and remarkable safety of TCM have been documented after controlled clinical studies, there are several herbal and animal parts that are toxic or difficult to identify. DNA polymorphism-based assays have recently been developed for the identification of herbal medicines. In this approach, small amounts of DNA are amplified by the polymerase chain reaction and the reactions products are analyzed by gel electrophoresis, sequencing, or hybridization with species-specific probes. With the DNA based identification of TCM materials as an example, chip-based analytical micro devices were developed with the goal of fabricating an integrated device that will enable sample preparation, amplification, and analysis on a single microchip-based device ("lab-on-a-chip"). The application of a silicon-based polymerase chain reaction microreactor and a DNA microarray for the DNA sequence-based identification of toxic medicinal plants is reported here.
No Title by Andreas Manz; Luc Bousse; Andrea Chow; Tammy Metha; Anne Kopf-Sill; Wallace J. Parce (pp. 195-201).
Synchronized cyclic capillary electrophoresis (SCCE) makes use of a closed loop separation channel by which the same sample can be separated during many cycles. This enables the repeated use of the same voltage for separations such that a high total voltage, and thus high efficiency, is obtained for the synchronized components. This can be accomplished by using any type of polygon geometry for the separation channel; and calculations of the available field and number of connections needed for polygons from 3 to 5 sides are presented. Triangular designs have the advantage of using the lowest number of wells. Such designs are described, with two additional features compared to that of earlier work: 1. voltage connections that are much shallower than the separation channel, to reduce losses and dispersion at the intersections; and 2. corners that are narrower than the separation channels to reduce dispersion in the turns.Experimental data is presented for the separation of a mixture of amino acids, and for a DNA separation in a polymeric sieving matrix. The DNA separation is most sensitive to the corner dispersion problem, which reduces the observed efficiency for that separation.
No Title by S. Lin; F. Tseng; H. Huang; C. Huang; C. Chieng (pp. 202-208).
A novel method of protein array immobilization, using micro stamps to pick up proteins from micro wells and deposit them on to a bio-absorption chip, has been developed. This method can potentially transfer several protein spots on to an organized array for applications such as disease diagnosis and drug screening by parallel biological or chemical processes. Fabrication of the micro stamp and the micro well arrays involves thick-photoresist lithography, bulk micromachining, and a molding process, whereas fabrication of the bio-absorption chip involves amino-modification by use of APTS (aminopropyltrimethoxysilane) and surface activation by use of BS3 (bis-sulfosuccinimidyl suberate). Successful transfer of protein on to the bio-absorption surface using the micro stamp-well array has been demonstrated. The size variation between different stamping spots has been shown to be less than 10%, and the APTS–BS3 surface has also been proved to bind the protein efficiently. Appreciable protein retention was achieved during 6-h washing, which shows the binding strength of the bio-absorption surface is sufficient for protein processing.
No Title by Katsumi Uchiyama; Wei Xu; Jingmiao Qiu; Toshiyuki Hobo (pp. 209-211).
A blue-light-emitting diode was incorporated as a fluorescence-excitation light source into a polyester microchannel chip fabricated by in situ polymerization. Placing the light-emitting facet of the diode close to the microchannel obviated any need for an additional optical arrangement. Fluorescence from the sample was transmitted by an optical fiber incorporated into the microchip perpendicular to the LED. FITC labeled amino acids were separated in the presence of 5 mM SDS by using the microchip and were detected by LED-induced fluorescence.
No Title by M. Wedig; M. Thunhorst; S. Laug; M. Decker; J. Lehmann; U. Holzgrabe (pp. 212-217).
For two years drugs introduced to the market have had to be enantiomerically pure. Rapid and cheap methods of high reproducibility must, therefore, be available for evaluation of enantiomeric purity. Within the framework of a larger project dealing with chiral recognition of phenethylamines by means of native and derivatized cyclodextrins it was intended to find capillary electrophoresis methods suitable for separation of the enantiomers of chiral bis(phenethyl)amines and their corresponding cyclic analogues, within 10 min, using small amounts of a chiral selector, to save time and money. Heptakis(2,3-O-diacetyl-6-sulfato)β-CD was found to be the most promising candidate most often fulfilling these requirements.
Micro flow modules with combined fluid flow channel and optical detection waveguide – hyper Rayleigh scattering as a case study by H. Fouckhardt; A. Grosse; M. Grewe; M. Kuhnke (pp. 218-227).
Micro flow modules with optical detection have been fabricated in a way which enables optical wave-guiding inside and a defined interaction length along the fluid channel. Because of the usually lower refractive index of the solution compared with that of the substrate, so-called "leaky" optical wave-guiding must be employed. The combination of the fluid flow channel function with that of the optical waveguide has advantages for all miniaturized optical detection cells. It has been shown for hyper Rayleigh scattering (HRS) that improvement of the analytical principle is inherent in the miniaturization. The detection limit can be enhanced by at least a factor of 20. The applied HRS measurement procedure also enables simultaneous detection of two photon absorption (TPA) fluorescence. The severe boundary conditions of capillary electrophoresis were used as micro flow module design constraints to enable the transfer of the approach to other types of analysis.
No Title by Benedikt Graß; Dirk Siepe; Andreas Neyer; Roland Hergenröder (pp. 228-233).
Conductivity detection is one of the most often employed means of detection in isotachophoresis. In microanalytical devices, thin-film platinum electrodes can be used for conductivity detection and for other electrochemical methods of detection. The design and the performance of different electrode geometries for on-column contact conductivity detection with thin-film platinum electrodes integrated on an isotachophoresis PMMA-microchip is described. Three different electrode geometries for direct conductivity detection were used for the investigation of isotachophoretic separations. The influence of the width of the electrodes and their positioning relative to the separation channel was investigated. The performance of the different detectors is compared for the analysis of organic carboxylic acid anions.
No Title by Dmitry A. Markov; Darryl J. Bornhop (pp. 234-237).
The current trend toward miniaturization of fluid-handling systems, particularly those of micro-fluidic devices on the capillary-scale, will certainly lead to improvements in chemical and biochemical analyses. Unfortunately, when fluid volumes reach nano- and picoliter scale it is problematic to perform non-invasive fast and accurate volume flow or flow velocity measurements. Here a simple, non-invasive method is presented for detecting and measuring linear flow velocity within fluid-filled capillaries. A small fluid volume is repeatedly heated locally by means of an infrared laser diode and using the micro-interferometric back-scatter detector (MIBD) at a fixed distance downstream, a thermally induced change in refractive index is observed when the heated volume traverses the probe volume of the detector. Fluid velocity is calculated by monitoring the phase difference between the second harmonic of the heating function and the resulting MIBD output in the Fourier domain. In a probe volume of 40 nL flow rates between 1 and 10 µL min–1 are quantifiable, with 3σ detection limits determined to be 42.8 nL min–1.
No Title by C. Mayer; N. Stich; T. Schalkhammer; G. Bauer (pp. 238-245).
The most fundamental properties of metal nanoclusters, namely the high local-field enhancement and nanoscale resonance behavior of the cluster electron plasma when exited by electromagnetic radiation, have been used to set up a variety of sensors transducing biorecognitive interactions into optical signals. This paper focuses on applications of resonant-cluster technology, which enabled us to monitor biorecognitive binding of a variety of proteins on a chip, thus constructing high-throughput interaction-screening devices.Decisive for this type of sensor is the nanometric distance from the local field surrounding a cluster to other parts of the sensor interacting with this field. In particular, the cluster–mirror or cluster–fluorophore distance gives rise to a variety of enhancement phenomena. Depending on the desired application this "resonance" – distance is approximately 5–400 nm.All types of sensor can be set up on photolithographically constructed microchips, but microscopic glass slides can also be employed; this also enables the use of standard devices for dotting and read out.Using slide based chips a standard format of 3200 microdots (125 µm in diameter) was the basis of either microassays applying direct optical transduction via surface-enhanced absorption or striking for more sensitivity via surface-enhanced fluorescence.
No Title by M. Trojanowicz (pp. 246-260).
Methods of in-vitro artificial formation of bilayer lipid membranes (BLM) and their analytical applications are reviewed, on the basis of 122 literature references. Different techniques for preparation of free-suspended planar BLMs, and gel-, filter-, and solid-supported systems are presented. The analytical applications developed are based on direct interaction of analytes with chemically unmodified BLMs, and with systems modified by use of redox mediators, ionophores, ion-channel forming species, enzymes, antibodies, or DNA.
No Title by Antoine Daridon; Valia Fascio; Jan Lichtenberg; Rolf Wütrich; Hans Langen; Elisabeth Verpoorte; Nico F. de Rooij (pp. 261-269).
A new, versatile architecture is presented for microfluidic devices made entirely from glass, for use with reagents which would prove highly corrosive for silicon. Chips consist of three layers of glass wafers bonded together by fusion bonding. On the inside wafer faces a network of microfluidic channels is created by photolithography and wet chemical etching. Low dead-volume fluidic connections between the layers are fabricated by spark-assisted etching (SAE), a computer numerical controlled (CNC)-like machining technique new to microfluidic system fabrication. This method is also used to form a vertical, long path-length, optical cuvette through the middle wafer for optical absorbance detection of low-concentration compounds. Advantages of this technique compared with other, more standard, methods are discussed.When the new glass-based device for flow-injection analysis of ammonia was compared with our first-generation chips based on silicon micromachining, concentration sensitivity was higher, because of the longer path-length of the optical cuvette. The dependence of dispersion on velocity profile and on channel cross-sectional geometry is discussed. The rapid implementation of the devices for an organic synthesis reaction, the Wittig reaction, is also briefly described.
No Title by Ellis Meng; Shuyun Wu; Yu-Chong Tai (pp. 270-275).
Several types of silicon fluidic coupler have been designed, fabricated, and tested to facilitate external connections to MEMS (microelectromechanical systems) fluidic devices. By using both bulk micromachining and DRIE (deep reactive ion-etching) techniques, couplers of different geometry have been produced for use with any standard MEMS fluidic port. In addition, couplers are easily modified to accommodate any arbitrary fluidic port geometry. For ease of use, these couplers interface with PEEK (polyetheretherketone) and fused-silica capillary tubing, both of which are commonly used in HPLC (high-performance liquid chromatography) systems and are supported by a wide range of plumbing products. Coupler performance was evaluated and an operating range of at least 0–8963 kPa (0–1300 psig) is attainable.
No Title by Yuichi Wakamoto; Ippei Inoue; Hiroyuki Moriguchi; Kenji Yasuda (pp. 276-281).
A method is described for continuous observation of isolated single cells that enables genetically identical cells to be compared; it uses an on-chip microculture system and optical tweezers. Photolithography is used to construct microchambers with 5-µm-high walls made of thick photoresist (SU-8) on the surface of a glass slide. These microchambers are connected by a channel through which cells are transported, by means of optical tweezers, from a cultivation microchamber to an analysis microchamber, or from the analysis microchamber to a waste microchamber. The microchambers are covered with a semi-permeable membrane to separate them from nutrient medium circulating through a "cover chamber" above. Differential analysis of isolated direct descendants of single cells showed that this system could be used to compare genetically identical cells under contamination-free conditions. It should thus help in the clarification of heterogeneous phenomena, for example unequal cell division and cell differentiation.