E. Verpoorte

Three-dimensional micro flow manifolds for miniaturized chemical analysis systems

A three-dimensional (3D) stack concept for the assembly of photolithographically fabricated microfluidic components is presented and discussed. The system uses silicon-based micropumps and simple planar structures which mimic standard elements of conventional flow systems. Detection is provided either by solid state electrochemical sensors or small volume optical detection. The general advantages of using micromachined flow manifolds for microchemical analysis are addressed. The particular benefits to be derived from this an approach compared with other assembly methods are also examined.

Fabrication of multilayer systems combining microfluidic and microoptical elements for fluorescence detection

This paper presents the fabrication of a microchemical chip for the detection of fluorescence species in microfluidics. The microfluidic network is wet-etched in a Borofloat 33 (Pyrex) glass wafer and sealed by means of a second wafer. Unlike other similar chemical systems, the detection system is realized with the help of microfabrication techniques and directly deposited on both sides of the microchemical chip. The detection system is composed of the combination of refractive microlens arrays and chromium aperture arrays. The microfluidic channels are 60 /spl mu/m wide and 25 /spl mu/m deep. The utilization of elliptical microlens arrays to reduce aberration effects and the integration of an intermediate (between the two bonded wafers) aluminum aperture array are also presented. The elliptical microlenses have a major axis of 400 /spl mu/m and a minor axis of 350 /spl mu/m. The circular microlens diameters range from 280 to 300 /spl mu/m. The apertures deposited on the outer chip surfaces are etched in a 3000-/spl Aring/-thick chromium layer, whereas the intermediate aperture layer is etched in a 1000-/spl Aring/-thick aluminum layer. The overall thickness of this microchemical system is less than 1.6 mm. The wet-etching process and new bonding procedures are discussed. Moreover, we present the successful detection of a 10-nM Cy5 solution with a signal-to-noise ratio (SNR) of 21 dB by means of this system.

A Silicon Flow Cell for Optical Detection in Miniaturized Total Chemical Analysis Systems

Abstract The applicability of silicon micromachining to the fabrication of a small-volume flow cell for UV-visible absorption detection is demonstrated. With volumes ranging from 1 to 100 nl and lengths of 1 and 5 mm, this type of cell has a long path length relative to its volume. Light is transported through the cell by means of a series of reflections, so that the optical path length may be increased to values beyond the actual cell length, depending on the input angle of the light. Preliminary experiments using a 1 mm, 15 nl cell to measure dye-containing solutions demonstrate an application of multireflection to the measurement of absorbance.

A novel approach to ion separations in solution : synchronized cyclic capillary electrophoresis (SCCE)

Abstract A novel concept for ion separation is presented. Repeated column switching in capillary electrophoresis allows for the elimination of unwanted sample components, and for the separation of species having very similar mobilities. Theoretical considerations predict good separation efficiencies, e.g., high plate numbers per volt. Using micromachining techniques, a planar glass structure has been fabricated, composed of four capillaries of 20 mm length arranged in a square. Laser fluorescence detection is used in the detection scheme. To move a component around one cycle, 1 min is needed when applying 2.5 kV. A demonstration of the peak band broadening after several cycles and a separation example are given.

Novel instrumentation for real-time monitoring using miniaturized flow systems with integrated biosensors

A prototype miniaturized Total Chemical Analysis System (μTAS) has been developed and applied to on-line monitoring of glucose and lactate in the core blood of anaesthetized dogs. The system consists of a highly efficient microdialysis sampling interface sited in a small-scale extracorporeal shunt circuit (‘MiniShunt’), a silicon machined microflow manifold and integrated biosensor array for glucose and lactate detection with associated computer software for analytical process control. During in-vivo testing the device allowed real-time on-screen monitoring of glucose and lactate with system response times of less than 5 min, made possible by the small dead volume of the microflow system. On-line glucose and lactate measurements were made in the basal state as well as during intravenous infusion of glucose or lactate. The prototype μTAS is currently suitable for trend monitoring but refinements are necessary before application of the system for determination of individual lactate values.

µ-TAS: Miniaturized Total Chemical Analysis Systems

The miniaturized total chemical analysis system is a concept for on-line monitoring combining classical analytical techniques and photolithographically defined micro structures. Examples of silicon and glass micro structures for flow-injection analysis, capillary liquid chromatography and capillary electrophoresis are given. The results obtained indicate faster separations, dramatically reduced reagent consumption, and access to novel types of analysis techniques.

Planar chip technology for capillary electrophoresis

Miniaturization of separation columns implies equally reduced volumes of injectors, detectors and the connecting channels. Planar chip technology provides a powerful means for the fabrication of micron sized structures such as channels. This is demonstrated with three examples. An optical absorbance detector chip exhibits the expected behavior of a 1 mm optical pathlength cell despite its volume of 4 nL. A capillary electrophoresis device allows for integrated injections of 100 pL samples, for efficiencies of 70 000 to 160 000 theoretical plates in 10 to 20 seconds, and for external laser-induced fluorescence detection at any capillary length of choice between 5 and 50 mm. A system for synchronized cyclic capillary electrophoresis is also presented in which plate numbers per volt can be dramatically increased.

Microsystems for Analysis in Flowing Solutions

A three-dimensional modular setup for a miniaturized analysis system for flowing streams is presented. The system uses silicon micromachined pumps and flow manifolds in combination with electrochemical sensors or optical detection. Applications range from simple ion concentration measurements with ISFETs to a multi-step chemical analysis of phosphate. Miniaturization of the flow systems leads to a substantial reduction in reagent consumption.

A Microfabricated Probe with Integrated Coils and Channels for on-Chip NMR Spectroscopy

We present the development of a monolithic NMR probe fabricated on a glass substrate, combining an integrated high-quality factor, multi-turn planar coil with a microfluidic network. Concentrations of a few percent ethanol in water can be detected by 1H NMR in a 30-nL volume with only 3 scans.

A novel optical detector cell for use in miniaturized total chemical analysis systems

The use of silicons optical and mechanical properties is demonstrated in a silicon-based, small-volume, optical flow cell. Cells having volumes ranging from 1 to 100 nL and lengths of 1 and 5 mm have been constructed using a basic micromachining process. Cell depths of 50 to 100 mu m and widths of 50 and 300 mu ms across demonstrate the applicability of silicon micromachining to fabrication of cells having dimensions not attainable by conventional machining methods. Utilization of silicon crystalline planes to couple light into and out of the cell through a series of reflections should improve detection limits obtainable using these cells, as effective optical pathlength can be increased beyond actual cell length.<<ETX>>