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For the past two decades intensive research has been carried out on the development of environmental sensors. Nevertheless, the applicability of such devices has been hindered by harsh work conditions and the complexity of the sample matrices. A novel approach centres on the integration of sample pre-treatment steps, where the technology involved can be used advantageously for the design of a Micro Total Analysis System (fluid motion and detection enhancement). The synergistic mixed surfactant system allows the development an independent "green" target specific extraction scheme. Amphiphiles are routinely used in the electrophoretic separation process for their intrinsic detection signal enhancement (i.e. by optical/electrochemical methods). They can also be regarded as a means of flow generation (e.g. Marangoni's Flow) in micro-systems. In this perspective, we are currently developing micro-systems based on glass and polymeric substrates (e.g. poly dimethyl silicone). Whilst the surface chemistry of glass substrates allows the integration of mesoporous silica and ceramics, soft lithographic methods, such as micro-moulding or prototyping, renders the design of PDMS substrate simple. While the selectivity of the system may be based on molecular imprinted silicates, biologically compatible ceramics such as titanium dioxide can be used for the design of a single optical/ electrochemical detection cell. All of these previously cited technologies form a standing bridge towards independent, automated, at-/on-line sensor systems.

Internal channel has been widely used in biotechnology applications such as DNA stretching, Micro total analysis system (µ-TAS), Lap on a chip and etc. Bulk machining with laser was developed as a direct writing method which focuses laser beam inside the bulk material and write a pattern inside the material. Femtosecond laser provides non-thermal multiphoton interaction with material, and thus results in high quality of channel. Compared to glass, polymer has several advantages in biomedical applications such as wide range of material properties, low cost, high toughness, and biocompatibility. In this paper, we are presenting a new method to fabricate internal channel inside PMMA with femtosecond laser and gas assisted material removal concept. The minimum diameter of 2µm was achievable and the maximum channel was achievable as long as 10mm.Internal channel has been widely used in biotechnology applications such as DNA stretching, Micro total analysis system (µ-TAS), Lap on a chip and etc. Bulk machining with laser was developed as a direct writing method which focuses laser beam inside the bulk material and write a pattern inside the material. Femtosecond laser provides non-thermal multiphoton interaction with material, and thus results in high quality of channel. Compared to glass, polymer has several advantages in biomedical applications such as wide range of material properties, low cost, high toughness, and biocompatibility. In this paper, we are presenting a new method to fabricate internal channel inside PMMA with femtosecond laser and gas assisted material removal concept. The minimum diameter of 2µm was achievable and the maximum channel was achievable as long as 10mm.

This paper describes a new method to fabricate large scale 3D weir-type filter for cell fractionation. The 3D structure is realized by a conformal bonding of two separate PDMS (poly-dimethyloxane) layers with in-situ microchannels which are formed by the conventional soft lithographic techniques. Moreover, the microfluidics channels on the two PDMS are set to cross to each other to increase weir numbers and flow throughput. The gap space of the weir filters depends on the thickness of the photoresist coated for the master formation, thereby it can be defined as required from submicron to hundreds micron scale. A white blood cells (WBCs) extraction experiments with the full polymer fabricated filters are conducted to validate the proposed method.. The experimental results show that the weir-type filter array can fractionate the WBCs well from blood samples. Due to its intrinsic advantages of rapid process, high throughput and low cost, the proposed method is very promising for being integrated into Micro Total analysis System (#956;TAS).

In this work, micro particle imaging velocimetry (micro-PIV) was performed on the fundamental components of a micro total analysis system. Specifically, high aspect ratio passive valves and mixers were designed, fabricated, and characterized. The components were built using Micralyne Protolyne technology on a glass substrate and operated at reasonably achievable pressures. The flows through the components were analyzed both qualitatively and quantitatively with the goal of developing a more complete understanding of internal device performance. Using the results of the micro-PIV developed velocity fields it was found that the high aspect ratio passive valves are able to perform at reasonably achievable pressures. However, it was determined that the high aspect ratio passive mixers offer limited performance enhancements because of the low Reynolds number flows. The results of this work contribute to the understanding of passive component operation and address some of the challenges associated with developing completely integrated micro total analysis systems that use passive devices.Copyright © 2005 by ASME

Micropumps are studied for applications to /spl mu/TAS (micro total analysis system) systems for automatic medication, and so on. The principals of the micropumps are using piezoelectric materials, SMA (shape memory alloy), etc. In this study, we propose a micropump using a magnetic micromachine. As the magnetic micromachines work wirelessly, we can obtain a wireless micropump that is suitable for the miniaturization. In previous studies, we examined the basic properties of the pump, and we found that the produced pressure could be controlled by the frequency of the applied rotational magnetic field. In this study, we examined the properties of the pump such as the pressure and the flow rate. In addition, we proposed a disposable pump system using the magnetic micromachine.

New concept of micro/nano tools working in water solutuon has been proposed by the author. A real three dimensional micro fabrication process using photo curable polymer named "micro/nano stereolithography" has been also developed by the author's group. The latest version of this process achieved 100 nm in 3D resolution and freely movable micro/nano mechanism are easily fabricated within 20 min. Nano tweezers and nano needle with two degrees of freedom were successfully fabricated without any assembly process. Cell and delicate biological materials can be remotely handled with neither any micro actuators nor lead wire. It was verified that this light-driven micro tool has precise force control with 10 FtN. These light-driven micro tools contribute to cellular biology as well as medical tools. The second application of microstereolithography is the biochemical IC chips for both micro chemical analysis and synthesis. Unlike conventional "lab. on a chip" and "micro total analysis system" (micro-TAS), our biochemical IC has micro pumps and active valves in one chip. Users can construct their own micro chemical device by themselves. The advanced biochemical IC chip-set for "on chip cell-free protein synthesis" has been prototyped and verified experimentally. A luminous enzyme of fire fly so called "Luciferase" and useful bio-marker protein "GFP" were synthesized successfully. According to above results, the biomchemical IC chips will be useful to "Order-made medicine" in near future.

A micro total analysis system (μ-TAS) is expected to reduce inspection time or the amount of reagent needed. Because of the small Reynolds number in a microchannel, mixing is performed mainly by diffusion. We have proposed an active method to stir a liquid by an optical mixer to improve efficiency. A fabricated optical mixer (SU-8, 20 μm in diameter) is secured inside a chamber at the focal point of the NA=1.4 objective lens and generates flows around it. We have analyzed the micro-liquid velocity vectors and the flux amount around three kinds of mixers (3, 4 and 5 wings) with an upward-directed YAG laser beam at different depths for both horizontal and vertical rotations.

We present a new rapid prototyping technique to produce a glass chip with high aspect ratio channel for micro total analysis system (/spl mu/TAS). This technique consists of powder blasting technique and laser patterning of newly developed Au nano-particles dispersed polymer mask. The microchannel with maximum aspect ratio of 2.1 in a glass substrate was successfully realized without photolithography step. The proposed technique was applied to a glass chip for electrophoresis and its performance for DNA separation analysis was confirmed. Furthermore, the micro-powder blasting technique with elevated temperature of Au nano-particles dispersed polymer mask was proposed for the first time.

Three-dimensional (3-D) microstructuring of photosensitive glass is demonstrated by using femtosecond (fs) laser for Lab-on-chip, in other words, micro total analysis system (μ-TAS), application. The fs laser direct-write process followed by a thermal treatment and chemical etching in a HF aqueous solution produces true 3-D hollow microstructures embedded in the photosensitive glass. This technique is applied for manufacturing a microfluidic structure inside the glass. Mixing of two kinds of aqueous solutions is demonstrated in the fabricated structure. A freely movable microplate is also fabricated inside glass to control a stream of reagents in the microfluidics. In the meanwhile, this technique is applied for integrating microoptics like micromirror and micro beam splitter in the glass chip for optical analysis of reactants produced in the microfluidics. This paper also discusses the mechanism of fs laser and photosensitive glass interaction.

Presented is a novel approach for an integrated micro total analysis system (microTAS) based on a microfluidic on-chip device that supports ultrasensitive confocal detection of fluorescent cells and particles and subsequently allows for their precise sorting in the fluid phase with respect to spectroscopic properties, such as brightness and color. The hybrid silicone elastomer/glass chip first comprises a branched channel system to initiate fluid mixing and to hydrodynamically focus the sample solution down to a thin flow layer, matching the size of the confocal detection volume placed at that position and, thus, providing a high detection efficiency. In the subsequent on-chip module, the dispersed cells or particles can be sorted into two different output channels. The sorting process is realized by a perpendicular deflection stream that can be switched electrokinetically. The performance of the automated sorting routine is demonstrated by precise partition of a mixture of differently colored fluorescent beads. Moreover, the specifically branched channel geometry allows for direct implementation of reaction steps prior to detection and sorting, which is demonstrated by inducing a selective recognition reaction between the fluorescent protein R-phycoerythrin and a mixture of live bacterial cells exhibiting or lacking the respective surface antigens.

This paper presents a novel fabrication method of in-channel three-dimensional micromesh structures using the conventional photolithography. The micromesh was realized by exposing UV light from the backside of the SU-8 coated metal-patterned glass substrate for different angles. Numbers of exposure and irradiation angle decided the shape and the size of micromesh. Based on this technique, three different micromesh-inserted microchannel structures were fabricated. For hydrodynamic characterization, their flow resistances were measured. Finally, for the application of micro total analysis system (/spl mu/TAS), the microfilter was fabricated and its filtering property was demonstrated.

Fluid handling integrated into microsystems has been in use now for a number of years. Mostly, research has focused on micro pumps, valves, sensor flow cells and electrophoresis. However, the underlying idea of shrinking the whole analytical chemistry or biochemistry lab down to chip size will make it necessary to talk about interfacing these modules properly and efficiently. Recently, we have proposed a concept for a chemical microprocessor. This concept is related to an earlier attempt to define an analytical chemistry microsystem, /spl mu/-TAS (miniaturised total analysis system).

One of the challenges of future miniaturized biochemical analysis laboratories is to manipulate sub-/spl mu/L samples in parallel fashion. Since the development and implementation of the 96-well microtiter plate technology, considerable progress has been made to increase the plate density. A number of high-density formats have been developed based on the well-established 96-well format, including 386, 864, and 1536 wells. The available sample handling systems, however, are lagging due to wide center-to-center spacing and inability to handle sample volumes below 0.5 /spl mu/L. Also, these systems are capable of dispensing only 6 to 12 pipettes at one time. With the current trends of miniaturizing biochemical analysis techniques and the drive toward the development of a Micro Total Analysis System (/spl mu/TAS), techniques must be developed to allow macroscale spatial manipulation of sub-/spl mu/L sample volumes in a highly parallel manner at sub-mm spacing In this work, we present an approach for macroscopic manipulation of pL to /spl mu/L fluid volumes and demonstrate the application to slab gel electrophoresis.

The field of microfluidics is developing rapidly with advances in MEMS (micro electro mechanical system) and μ TAS (micro total analysis system) technologies. In various devices, controlling the flow rate of liquid or gas accurately at micro or nanoliter volume levels is required. In this work, the gas-liquid two-phase flow patterns in a microchannel T-junction have been examined. The two-phase flow patterns were observed in the T-junction under two different gas and liquid injection conditions. The flow patterns of liquid and gas in the microchannel after the T-junction were also observed and classified into three types depending on the flow rate, and a two-phase flow pattern map was constructed. The mechanism of bubble breakup at a micro T-junction was also experimentally and analytically investigated.Copyright © 2003 by ASME

In order to realize a medical micro total analysis system in practical use, a partly disposable 3-way microvalve was developed. The separate channel structure and pneumatic actuation are employed considering the problems of whole blood handling. It has the advantages of easy assembly, large on/off flow ratio (about 10/sup 4/), no bubble problem, low cost due to the partly disposable structure and perfect process matching to micro chemical sensors (amperometric sensors or ISFETs).

A microfabricated capillary electrophoresis chip has been recently developed and many researchers have reported its attractive potentials such as the drastic increase of speed, reduced sample volumes, higher resolutions and so forth. Furthermore the more aggressive strategy is to integrate a variety of components of analysis system on a chip and has been rapidly developed as so-called "/spl mu/-TAS (micro total analysis system)", which is composed of microchannel network for sample pre- and post treatment, chemical reactions and separations and also detection systems like bio/chemical sensors, microoptics and microelectronic devices. In order to achieve the health care device that allows short-time inspection of human body by analyzing a slight amount of body fluid like blood, urine or saliva, we have been developing the micro analysis devices, and so far on-chip analysis of blood cells and serum have been studied based on micro-capillary electrophoresis chips. In this article, for the purpose of on-chip cell and/or particle separation and manipulation, (1) a separation of the serum and blood cells from the whole blood using a centrifugal chip, and (2) cell trapping using interdigitated electrodes have been investigated.

Immobilized bioelements offer additional sensitivity and/or selectivity in analytical techniques, in biotechnological devices, and in different medical applications. Great research interest has recently been focused in all these fields on miniaturization techniques, special attention being accorded to the patterning of biomolecules (e.g. enzymes) on solid surfaces with micrometer resolution. Novel microanalysis systems consider the use of enzyme microstructures as e.g. part of mu- Total Analysis System platforms as biochemical microreactors or detection units. This mini-review highlights recent advances in the creation of enzyme microstructures by indirect methods (photolithography, microcontact printing. etc.) and active placement methods (electrospraying, microdispensing, etc.). Some key visualization techniques of enzyme microstructures (fluorescence microscopy, scanning electrochemical microscopy, etc.) are also mentioned together with examples of their applications or application possibilities. (Less)

A continuous flow micro total analysis system (micro-TAS) consisting of an on-chip microfluidic device connected to a matrix assisted laser desorption ionization [MALDI] time-of-flight [TOF] mass spectrometer (MS) as an analytical screening system is presented. Reaction microchannels and inlet/outlet reservoirs were fabricated by powderblasting on glass wafers that were then bonded to silicon substrates. The novel lab-on-a-chip was realized by integrating the microdevice with a MALDI-TOFMS standard sample plate used as carrier to get the microfluidic device in the MALDI instrument. A novel pressure-driven pumping mechanism using the vacuum of the instrument as a driving force induces flow in the reaction microchannel in a self-activating way. Organic syntheses as well as biochemical reactions are carried out entirely inside the MALDI-MS ionization vacuum chamber and analyzed on-line by MALDI-TOFMS in real time. The effectiveness of the micro-TAS system has been successfully demonstrated with several examples of (bio)chemical reactions.

Flow cytometry (FCM) has applications in biodefense, clinical, and environmental analysis of microbial populations [1]. Currently, the widespread use of FCM is limited by the size and cost of multi-color instruments. This paper describes a two-color micro-integrated flow cytometer (MIFC) which is novel with respect to 1) the configuration of fiberoptics within a disposable microfluidic system, and 2) the implementation of diode lasers, LEDs, and low-cost PIN photodetectors in a total analysis system with high signal to noise ratio (S/N). The MIFC (Fig. 1) has been validated using biological samples, and can reduce the size and cost of FCM by two orders of magnitude for portable, hand-held applications.

A miniaturized flow system was constructed for the analysis of cells immobilized on a silicon micro(µ)chip. Cell viability was tested by stimulating the cells with sucrose, followed by monitoring the production of glucose (GL) and ethanol (ET), using a µ-chip based enzyme catalyzed chemiluminescent (CL) reaction.

DNA amplification with polymerase chain reaction (PCR) is often performed in a batch process using a bench-top thermal cycler or in a micromachined PCR chamber. Recent effort has shown a continuous flow through PCR system can be realized by a time-space conversion in the PCR system [1]. Devices of this kind open up new areas of application in medical diagnostics, such as the online amplification and monitoring of a specific gene. Here we take advantage of the vertical integration capability of multi-layer ceramic technology and demonstrate a miniaturized cyclic PCR device. A cyclic device promises much smaller footprint and ease of integration into a micro total analysis system.

In the latest ten years, great efforts have been taken to miniaturize the biochemical and chemical analysis systems, and many kinds of biochips with functions of biology sample preparing, chemical assay reacting and result detecting, or mixture of some of these functions have been reported. An aspherical micro lens array with large numerous aperture is developed for a biosensor to achieve high fluorescence collection and high sensitivity. The optimized design and fabrication with new organic-inorganic sol-gel materials of micro lens arrays are discussed in this paper. Because of merits of micro size, low cost, facility to reproduce, flexibility to design and multi-channels detection, these elements are suitable to form a compact, multi-channel fluorescence biosensor that can address multiple biology samples simultaneously without loss in detection sensitivity. Packaging and alignment strategies for a sensor consist of micro lens arrays detecting fluorescence labeled DNA assay arrays are also presented, which is promising to be integrated into a micro total analysis system (u-TAS).

The integration is discussed of all parts of a microdialysis-based micro Total Analysis System or /spl mu/TAS. In particular a microdialysis probe, a potentiometric and amperometric ion- and enzyme sensor and a calibration dosing pump have been developed separately using different precision machining techniques. By modifying and adapting these parts they can be realized in one generic technology consisting of a stack of a silicon and a glass wafer. The silicon wafer contains the double lumen microdialysis probe connections, a dosing pump chamber with meander formed cavities containing the calibration solutions and small cavities for both the potentiometric and amperometric sensor. The glass wafer contains all the electrical contacts and wires for the sensors, the pump and Interconnections. Both wafers are anodically bonded to each other, yielding a hermetically sealed liquid handling system.

A novel integrated optical biosensor, that combines optical planar waveguides for illumination with microlens arrays for collection of fluorescence, is presented in this paper. This sensor is based on laser induced fluorescence detection and will be applied for biochemical or chemical applications such as fluorescence labeled DNA affinity assay. An evanescent field is generated by the optical planar waveguides, which illuminate DNA arrays on the surface of the waveguide. High signal to noise ratio and sensitivity can be achieved since the evanescent field is tightly confined within the neighborhood of the surface of waveguides and laser noise will scarcely reach the detector. Micro lens arrays with large numerous aperture are combined into the sensor to collect more fluorescent lights from DNA samples induced by the evanescent field. A high sensitive CCD is used for this multi-channel system. The sensor has advantages of compactness, multi-dimensional channel detection simultaneously, high sensitivity and good compatibility with biology samples, so it is not only suitable to be used in detection of fluorescent labeled DNA arrays, but also can be used in other life science research like fluorescence immunoassays. The compact design of the sensor allows it to be integrated in a micro total analysis system ((mu) -TAS) such as a portable DNA diagnostics device.

Based on laser induced fluorescence detection a miniaturized and sensitive optical system is developed for micro total analysis systems (u-TAS) application. A micro optical system integrated with a micro fluid device is a convenient way to realized biochemical reaction and detection on one chip. Such a bi-functional micro system for DNA affinity assay is presented in this paper. The optical system composed of optical fiber coupling with planar waveguide for illuminating the labeled DNA samples, and micro lens arrays for collecting the induced fluorescence light. High signal-to-noise ratio can be achieved because of evanescent field excitation mode. A specially designed micro chamber, with chemical process, including small pipes for guiding sample agent is included in the system in order to enable DNA affinity reaction, and to wash the chamber afer reaction. These components will be integrated within the encapsulation of a photoelectric array detector, so the size of this system can be greatly reduced. This bi-functional micro system has merits of integration of reaction and detection together, more compactness, multi-channel detection, high sensitivity and good compatibility with biological samples. This system is a promising candidate to be integrated into a micro total analysis system, such as a portable DNA diagnostics device.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Since the first work into miniaturisation technology by the micro-electronics industry, many branches of science have continued to follow this trend with the production of micro-sized instruments, one notable example was the manufacture of a miniature GC by Terry et al [1] in 1979. However it has only recently become apparent that the name micro-chip does not only apply to those devices found within complex computers and simple wrist watches. The name has also been taken by analytical chemists to describe a miniature appliance capable of performing the functions of a macro-scale system, whilst only a few centimetres in size. This “lab-on-a-chip” concept stems from the idea of the total analysis system (TAS). These complicated instruments which employ the capabilities of an entire lab, i.e. sampling, storage, pre-treatment, analysis, detection and data evaluation initiated the production of the micro-TAS (μ-TAS). These miniature total analysis systems embody the functions of the TAS whilst providing faster sample processing, higher efficiency and lower reagent consumption than conventional TAS. In addition, μ-TAS allow in-situ measurement due to their reduced dimensions and portability.

A silicon-machined micromixer[1] has been coupled with electrospray ionisation mass spectrometry (ESI-MS) as a step toward the development of a µSYNTAS (miniaturized-SYNthesis and Total Analysis System).[2] The micromixer has been successfully used for the synthesis of small organic molecules via C-C and C-N bond-forming steps. The potential utility of this device for the production of compound libraries is demonstrated through a multicomponent reaction, thus illustrating a possible methodology for combinatorial synthesis.

In this paper, we describe the design, fabrication, and testing of a prototype microvalve which makes use of a novel magnetic microactuator. The completed device consists of three layers, with the bottom two layers making up the normally closed valve. The top layer (actuator) contains the flux generator on its top surface combined with Ni/Fe plated through holes for guiding the flux to the valve. The actuator and valve components are separately fabricated and then attached to form the completed device. Preliminary test results show that the valve is capable of controlling gas flow in the range of tens to hundreds of (mu) L/min. This device will, therefore, be useful in its target applications, which is a microfluidic total analysis system ((mu) TAS) that will require precise valving at moderate flow rates (about 100 (mu) L/min).

There are several different approaches to bioanalytical measurements, including biosensors, flow injection analysis, and separation techniques such as capillary electrophoresis. Automating the use of all these techniques usually involves incorporation into flow systems, a concept which is known as the total analysis system (TAS). Optimization of analytical performance in most flow systems, particularly those which are based on high resolution separation methods, can be accomplished through miniaturization of the system to a μTAS. The use of microfabricated devices has become a popular approach for realizing miniaturized analysis systems for measurements on a sub-μL scale. This presentation will focus on the use of μTAS-type systems, both biosensor and non-biosensor based, for biosensing applications. A brief introduction to the analytical methods available for adaptation to bioanalytical μTAS is included in this review. Finally, the potential of μTAS to combine the best aspects of both stand-alone biosensors and benchtop biosensing systems will be discussed.

The combination of electrochemical transducers made in silion technology with chemical and biochemical components has been used to manufacture miniaturized sensor structures. Three different types of sensors have been developed and optimized for practical use: (i) an ion-selective sensor, (ii) a glucose enzyme sensor, (iii) a redox-amplifying sensor for immunosensing. The immunodetection based on the redox recycling of mediator molecules is shown for low and high molecular weight analytes. The sensors have been integrated with miniaturized fluidic components and combined with sensor-related electronics and a common microcontroller.

The development of miniaturized analytical systems has gained considerable momentum in the last few years. Planar micro-optics and solid state light sources have a great potential for reducing the size and simplifying the architecture of analytical systems1. Our investigation is focused on microlens arrays for μTAS. Arrays of refractive microlenses (2 μm to 5 mm lens diameter) have been fabricated by melting resist technology and replicated in polycarbonate and PMMA by embossing and casting techniques. Microlens arrays have been integrated into miniaturized analytical systems.

This Chapter has two purposes: The first purpose is to illustrate in some detail a design of an advanced chemical microsystem, also called a micro total analysis system (μTAS) 1 which can use either surface acoustic wave or optical chemical sensors in the test chamber, and which can be fabricated by silicon micromachining technology and semiconductor-glass bonding techniques; this μTAS can acquire data from chemically sensitive devices located in an ambient fluid, transform them in a suitable format for further signal processing and perform internal flow management and control; The second purpose is to present and discuss the Rome Tor Vergata electronic nose (EN), applied as an example in this paper to food analysis, using quartz micro balance (QMB) sensors and metallo-porphyrines as promising chemically interactive materials (CIM’s). The current study on QMB sensor matrices is considered and oriented to achieve all the necessary information for the development of the more advanced μTAS introduced above.

A new type of flow cell has been developed for detection of heavy metal ions in aqueous solutions, based on the flow injection method. The cell contains two chemically modified field effect transistors (CHEMFETs) of which one is selective for the supporting electrolyte ion (in this case a 0.1 M potassium ion solution) and the other is selective for the heavy metal ion to be detected (Cd2+, Pb2+). The differential signal of the reference electrode CHEMFET and the heavy metal ion CHEMFET in the flow cell system which has been presently developed will be evaluated for miniaturization and further integration in a micro total analysis system.

Microanalysis systems which are built up in a modular way can be adapted to various applications by exchanging individual modules. Thus, a bigger number of units can be sold and prices reduced. At the Karlsruhe Nuclear Research Center a microfluidic handling module is being developed which will be used in two different microanalysis systems joined with sensor modules. A batch fabrication process has been developed which was used to manufacture micropumps and microvalve systems by assembly of two molded thermoplastic parts and transfer of a polyimide diaphragm from a silicon wafer.

By comparing the developments taken place in the field of consumer electronics, where large scale equipment has been miniaturized due to the integration of electronic functions in one and the same chip, it is made clear how in the same way the present large scale equipment for chemical analysis might be miniaturized to portable µTAS systems. The progress in silicon sensor technology as well as in the micro systems technology for liquid handling systems makes this miniaturisation possible, but for the practical realisation of µTAS systems a standardisation for the interconnection of the system components has to be developed.

A new concept for miniaturised analysis systems, based on a modular assembly of silicon system components on a anodically bonded base plate containing fluid channels, is presented. The proposed configuration allows the separate development of the different system elements as well as an easy modification of the system setup. Besides micropumps and flow-sensors, for detection, different ISFET-based chemical sensors for cations are presented. Using covalent attachment of all membrane components to the polymer matrix, a durable CHEMFET system is obtained. It is shown that such sensors can be very well incorporated in a continuous flow system, e.g. a Flow Injection Analysis (FIA) system. Finally, the realization of a liquid dosing module and a modular setup for a Micro Total Analysis System (μTAS) is illustrated. Possible applications of such μTAS are discussed, and future markets are indicated.

Parylene-C has been widely used as a biocompatible material for microfluidics and micro total analysis system (microTAS) applications in recent decades. However, its autofluorescence can be a major obstacle for parylene-C based devices used in applications requiring sensitive fluorescence detection. In this paper, Parylene-C was compared with other commonly used polymer and plastic materials in microTAS devices for their autofluorescence. We also report here an in-depth study of the behaviors and mechanisms of the autofluorescence of parylene-C, as well as several other commercialized members in the parylene family, including parylene-D, parylene-N and parylene-HT, using epifluorescence microscopy, fluorimeter and infrared spectroscopy. Strong autofluorescence was induced in parylene-C during short-wavelength excitation (i.e. UV excitation). Variation of autofluorescence intensity of parylene-C film was found to be related to both dehydrogenation and photo-oxidation. Moreover, the influence of microfabrication process on parylene-C autofluorescence was also evaluated. Parylene-HT, which exhibits low initial autofluorescence, decreasing autofluorescence behavior under UV excitation and higher UV stability, can be a promising alternative for microTAS applications with fluorescence detection.

Here we report an approach utilizing a suspended nanoparticle crystal (S-NPC) as an electrical read-out biosensor based on a nanofluidic electrokinetics principle. As a preliminary demonstration, streptavidin-modified S-NPC with a particle diameter of 520 nm was used to detect biotin in a PBS buffer. The present result indicated that the detection range of biotin by this nanofluidics-based biosensor was about 1 nM-10 muM (in 10(-4)x PBS) with a sensitivity of 160 nS/nM. Being easy to get established, low-cost, and having large electrical read-out signal, the present S-NPC is believed to be a promising biosensing scheme in the micro total analysis system.

We fabricated a device equipped with a microchannel on a complementary metal oxide semiconductor (CMOS) sensor to observe the optical polarization rotation angle during in situ monitoring. The sensor is based on the integrated wire-grid polarization detection method. The microchannel is fabricated on a Si layer by deep reactive ion etching (DRIE). Using this device, we measured the optical rotation of chiral molecules in a microfluid. This showed that the device is applicable to in situ chiral measurement. Optical rotation angles of the linearly polarized light corresponded to different concentrations of sucrose solution. Sensor output reflecting the temporal concentration change of chiral molecules was also observed. These results clearly demonstrate that the CMOS sensor has the capability of measuring chiral molecules in situ.

We generated an aqueous two-phase laminar flow in a microfluidic chip and used the system to isolate leukocyte and erythrocyte cells from whole blood cells. The microfluidic system reduced the effect of gravity in the aqueous two-phase system (ATPS). Poly(ethylene glycol) (PEG) and dextran (Dex) solutions were used as the two phases, and the independent flow rates of the solutions were both 2 microL/min. When hydrophobic and hydrophilic polystyrene beads were introduced into the microfluidic device, the hydrophilic beads moved to the Dex layer and the hydrophobic beads to the interface between the two phases. In the case of living cells, Jurkat cells and erythrocytes moved more efficiently to the PEG and Dex layers, respectively, than they move in a conventional ATPS. When whole blood cells were inserted into the microfluidic chip, leukocytes could be separated from erythrocytes because erythrocytes moved to the Dex layer while leukocytes remained outside of this layer in the microfluidic system. The reported microfluidic chip for the whole blood cell separation can effectively be integrated into a Micro Total Analysis System designed for cell-based clinical, forensic, and environmental analyses.

We have studied the micro total analysis system as a blood test. A microfluidic device with a three-pronged microchannel and artificial capillary vessels was fabricated. The microchannel is to transport blood, focus blood cells, and line them up. The vessels are to observe red blood cell deformation. An excimer laser was used to form grooves and so on. Numbers of thermosetting resin film and fluororesin were piled up on a cover glass. A laser fabricated part of the channel at the each film every lamination, and then a three-dimensional structure microchannel was fabricated. The channel sizes have widths of 50-150 microm and depths of 45 mum. Through holes used as artificial capillary vessels are made in the fluororesin having a minimum diameter of 5 microm and a length of 100 microm. As blood and a physiological saline are injected into the microchannel, the device stands upward facing the channel, and blood cells go into the vessels by the force of gravity and sheath flow of the saline. By gravity various groove patterns were made changing the width and length for measurement of blood focusing. Moreover, the red blood cell deformation was observed in the vessels with a microscope.

The prevailing approach to cellular molecular analyte investigations employs lysis. Using analogies with automobiles, we explain how current practise ridicules cellular individuality and meaningful variation. Single cell analysis and micro total analysis system (microTAS) prospects are discussed.

This paper describes an application of surface acoustic wave for micro fluid systems. Owing to its high sensitivity, fabrication easiness, and actuation capacity, current SAW devices are widely used as a chemical sensor and linear motor [Takahashi et al. IEEE Trans. Ultrason. Ferroelectri. Frequ. Control 43, 901 (1996)] as well as SAW devices including filters and SAW‐Tag in the field of mobile communication. Furthermore, its applications for actuators in liquid such as liquid streaming [Shiokawa et al., Jpn. J. Appl. Phys. 28(28‐1), 126–128 (1989)] and atomizer [Kurosawa et al., Sensors Actuators A 50, 69 (1995)] are very attractive for micro fluid systems such as a micro injector, a micro total analysis system, and a lab‐on‐chip. In this paper, we propose and evaluate a novel fluid actuator device for micro fluid systems using Rayleigh waves. One of the important issues is a micro pump and fluidic friction of the micro channel for TAS. The surface acoustic wave is one solution for the issue. Some of the fluid dynamics will be discussed.

A new biosensing system is described that is based on the aggregation of nanoparticles by a target biological molecule and dielectrophoretic impedance measurement of these aggregates. The aggregation process was verified within a microchannel via fluorescence microscopy, demonstrating that this process can be used in a real time sensor application. Positive dielectrophoresis is employed to capture the nanoparticle aggregates at the edge of thin film electrodes, where their presence is detected either by optical imaging via fluorescence microscopy or by measuring the change in electrical impedance between adjacent electrodes. The electrical detection mechanism demonstrates the potential for this method as a micro total analysis system (microTAS).

The development of a microfluidic biosensor module with fluorescence detection for the identification of pathogenic organisms and viruses is presented in this article. The microfluidic biosensor consists of a network of microchannels fabricated in polydimethylsiloxane (PDMS) substrate. The microchannels are sealed with a glass substrate and packed in a Plexiglas housing to provide connection to the macro-world and ensure leakage-free flow operation. Reversible sealing permits easy disassembly for cleaning and replacing the microfluidic channels. The fluidic flow is generated by an applied positive pressure gradient, and the module can be operated under continuous solution flow of up to 80 microL min(-1). The biosensor recognition principle is based on DNA/RNA hybridization and liposome signal amplification. Superparamagnetic beads are incorporated into the system as a mobile solid support and are an essential part of the analysis scheme. In this study, the design, fabrication and the optimization of concentrations and amounts of the different biosensor components are carried out. The total time required for an assay is only 15 min including sample incubation time. The biosensor module is designed so that it can be easily integrated with a micro total analysis system, which will combine sample preparation and detection steps onto a single chip.

We describe the development of a micro total analysis system for the detection of ochratoxin A (OTA) in wine and beer. The OTA detection strategy is based on an indirect competitive ELISA detection by chemiluminescence with the integration of microfluidics with microfabricated amorphous silicon photodiodes fabricated on glass substrates [1] . The full lab-on-chip (LoC) assay is implemented on a prototype device for fully-automatic measurement and monitoring of photodiode signals and control of fluid handling. The device is composed of three peripheral control and measurement modules: a peristaltic pump, a fluid dispenser for fluid handling, and a multi-sensor data acquisition with custom transimpedance amplifier. A microcontroller interfaces the individual modules with a computer via USB communication. The analysis is run automatically and the results displayed through a PC controlled user interface. OTA was detected in wine and beer extracts down to 0.5 ng/mL.

DNA extraction automation is a major concern in molecular diagnostic where processing of numerous and daily samples of blood represent a labor-intensive task and are difficult to automate. With the rapid growth in the area of DNA diagnostics, there is an URGENT need for the development of a micro total analysis system which can do all the three main steps involved during nucleic acid-based diagnostics: sample preparation, extraction of the DNA, detection and quantification on one SINGLE chip. This work presents design, fabrication and testing of an integrated system, which can extract and electrochemically quantify DNA simultaneously from any unknown sample on one single chip. The system is fabricated using aluminum oxide membranes (AOM) as substrates for the extraction and quantification of DNA, bonded with the PDMS (Polydimethylsiloxane) block for providing the microfluidic inlet and outlet. Cost effective fabrication methods such as xurography (knife plotter) and soft lithography are used to obtain integrated hybrid fluidic and detector prototypes.