Miniaturized Analysis Systems

The need for improved sensor performance has led to the emergence of micro and nanofluidics. These fields seek to develop miniaturized analysis systems that combine the desired attributes in a compact and cost-effective setting. These platforms are commonly labeled as labs-on-chip or micro total analysis systems (pTAS)2, often using optical methods to realize a desired functionality. The preeminent role that optics play has recently led to the notion of optofluidics as an independent field that deals with devices and methods in which optics and fluidics enable each other3. Most of the initial lab-on-chip advances, however, occurred in the area of fluidics, while the optical components continued to consist largely of bulk components such as polarizers, filters, lenses, and objectives. 

Upadhyay, S., Ohgami, N., Kusakabe, H., and Suzuki, H., Electrochemical determination of gamma-glutamyl transpeptidase activity and its application to a miniaturized analysis system Biosens. Bioelec., 21, 1230,2006. 

Lab-on-a-Chip Micrototal analysis system (pTAS) Miniaturized analysis systems... 

Hill M, Harris N (2007) Ultrasonic particle manipulation. In Hardt S, Schbnfeld F, editors. Microfluidic Technologies for Miniaturized Analysis Systems. Springer Science + Business Media LLC, New York, USA. p 357-383. 

Hardt S, Schonfeld F (2007) Microlliudic technologies for miniaturized analysis systems. Springer, New York... 

Requirements for miniaturized analysis systems 2.1 DESIRED SYSTEM CHARACTERISTICS... 

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... 

In its most elementary version as depicted in Figure 1, a miniaturized analysis system has been used for the measurement of ion concentrations with ion sensitive field effect transistors (ISFET). The system comprises two pumps and two multi-ISFET detector cells, one of which acts as a reference. Preliminary experiments have been performed with a functional model of the system where the individual elements were connected with lengths of silicone rubber tubing. Measurement of potassium concentrations using an ISFET with a valinomycin / PVC membrane in a glass flow through cell showed the feasibility of the setup [8]. 

These new methods open up completely new possibilities concerning chemical analysis and chemical reactions It is now possible to fabricate highly efficient analysis systems with short analysis times, high efficiency and low reagent consumption [4] Miniaturized analysis systems enable field analysis and additionally it is possible to develop disposable systems which are highly significant for medical applications... 

Figure 2 Basic setup for a miniaturized analysis system. (Adapted from ref. 10)...

Micro Total Analysis Systems (pTAS) are chip-based micro-channel systems that serve for complete analytics. The word Total refers to the monolithic system character of the devices, integrating a multitude of miniature functional elements with minimal dead volumes. The main fields of application are related to biology, pharmacology, and analytical chemistry. Detailed applications of pTAS systems are given in Section 1.9.8. Recently, pTAS developments have strongly influenced the performance of organic syntheses by micro flow (see, e.g., [29]). By this, an overlap with the micro-reactor world was made, which probably will increase more and more. 

N., WiDMER, H. M., p-TAS miniaturized total chemical analysis systems, in Proceedings of the Micro Total Analysis System Workshop, pp. 5-27 (Nov. 1994), Enschede, The Netherlands. 

Bergfeld, P. (Eds.), Proceedings of the 2nd International Symposium on Miniaturized Total Analysis Systems,... 

Cowen, S. and Craston, D. H., An on-chip miniature liquid chromatography system design, construction and characterization, in Micro Total Analysis Systems, van den Berg and Bergveld, Eds., Kluwer Academic, The Netherlands, 1995, 295. 

The field of on-chip solution-phase synthesis and analysis, termed pSYN I AS (miniaturized-SYNthesis and Total Analysis Systems) is a rather new field in or-... 

A.J. Tudos, G.A.J. Besselink, and R.B.M. Schasfoort, Trends in miniaturized total analysis systems for point-of-care testing in clinical chemistry. Lab on a Chip 1, 83-95 (2001). 

Lu H, Schmidt MA, Jensen KF (2001) Photochemical Reactions and On-Line UV Detection in Microfabricated Reactors. Lab Chip 1 22-28 Manz A, Harrison DJ, Verpoorte EMJ, Fettinger JC, Ludi H, Widmer HM (1991) Miniaturization of Chemical-Analysis Systems - A Look into next Century Technology or just a Fashionable Craze. Chimia 45 103-105 McCreedy T (1999) Reducing the Risks of Synthesis. Chem Ind 15 588-590 McCreedy T (2000) Fabrication Techniques and Materials Commonly Used for the Production of Microreactors and Micro Total Analytical Systems. Trac Trends Anal Chem 19 396-401... 

Miniaturized chemical analysis systems have been developed for most macroscopic counterparts (Dittrich et al. 2006). The availability of optical fibers, light sources, and detectors in the visible UV and near-infrared (NIR) wavelengths makes it possible to integrate spectroscopic measurements in microreactors (Lobbecke et al. 2005). Fourier transform infrared spectroscopy (FTIR) is an efficient, broadly applicable... 

Manz, A., Graber, N., and Widmer, H. M. (1990). Miniaturized total chemical analysis systems a novel concept for chemical sensing. Sens. Actuators B Chem. Bl, 244—248. 

Harrison, D. J., Glavina, P. G., and Manz, A. (1993). Towards miniaturized electrophoresis and chemical analysis systems on silicon an alternative to chemical sensors. Sens. Actuators B Chem. BIO, 107-116. 

De Mello et al. have constructed a so-called pSYNTAS (miniaturized synthesis and total analysis system). The system was used to perform an Ugi-type reaction to form several a-aminoacetamides from amines, isocyanates and formaldehyde in the presence of water (Scheme 25) [56-58]. The reported system consists of a glass/silicon nanoreactor [59] in connection to a TOF-MS for the real-time online analysis of the reaction stream. Reactions were conducted in the 600 nl volume chip under continuous flow of 20-2 pl/min flow rate. Reduced flow rates resulted in increased outputs. The analyzed outlet flow showed high yields of the desired products with small quantities of starting materials and intermediates (no exact yields were reported). 

Janasek, D., Franzke, J., and Manz, A. 2006. Scaling and the design of miniaturized chemical-analysis systems. Nature 442 374-80. 

Three-dimensional (3D) structuring of materials allows miniaturization of photonic devices, micro-(nano-)electromechanical systems (MEMS and NEMS), micro-total analysis systems (yu,-TAS), and other systems functioning on the micro- and nanoscale. Miniature photonic structures enable practical implementation of near-held manipulation, plasmonics, and photonic band-gap (PEG) materials, also known as photonic crystals (PhC) [1,2]. In micromechanics, fast response times are possible due to the small dimensions of moving parts. Femtoliter-level sensitivity of /x-TAS devices has been achieved due to minute volumes and cross-sections of channels and reaction chambers, in combination with high resolution and sensitivity of optical con-focal microscopy. Progress in all these areas relies on the 3D structuring of bulk and thin-fllm dielectrics, metals, and organic photosensitive materials. 

Further progress of ECL probes immobilization methods should result in new robust, stable, reproducible ECL sensors. Especially, the use of electrochemilumi-nescent polymers may prove to be useful in this respect. There are also good prospects for ECL to be used as detection in miniaturized analytical systems particularly with a large increase in the applications of ECL immunoassay because high sensitivity, low detection limit, and good selectivity. One can believe that miniaturized biosensors based on ECL technology will induce a revolution in clinical analysis because of short analysis time, low consumption of reactants, and ease of automation. 

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