Microfluidic lab-on-a-chip systems based on polymers—fabrication and application

https://doi.org/10.1016/j.cej.2004.01.016Get rights and content

Abstract

In the future, plastic-based lab-on-a-chip systems will play a crucial role in modern life sciences, e.g. biotechnology and (bio)medical engineering. Presently, microfluidic systems for capillary electrophoresis (CE) are being used. They allow for the safe handling of smallest substance volumes in the pL range and their separation into the individual components. From the microtechnical point of view, current R&D activities mainly focus on the development of inexpensive fabrication methods. Low-cost CE systems may be obtained by plastic molding techniques on a polymer basis. First separations of biological fluids and inorganic ion solutions have been performed successfully.

Introduction

Microfluidic systems increasingly gain importance in modern life sciences as well as in diagnostic and therapeutic biomedical engineering.

Special types of microfluidic and nanofluidic structures are applied in so-called micro total analysis systems (μTAS) [1] and lab-on-a-chip systems [2], in miniaturized drug delivery systems as well as in areas of tissue engineering [3].

These are predominantly passive microcomponents, e.g. simple microdepressions that are frequently applied in conventional microtiter plates as reservoir areas or miniaturized sample chambers, so-called wells. Miniaturized analysis systems are additionally equipped with capillary microchannel structures, mainly in the form of inlet or supply channels or as reaction or separation sections. Microchannels with integrated microcomponents may take over either mixing or filter functions. Via smallest pores, a precisely adjusted sample transfer into and from microfluidic systems can be achieved [4].

Active microcomponents comprise, e.g. smallest pumping or valve systems that are mostly found in rather complex μTAS systems [5].

Hence, lab-on-a-chip systems represent special μTAS systems that are usually designed for a certain and well-defined analytical task. As presently there is a considerable need for miniaturized separation systems in various areas of modern life sciences (biotechnology, pharmaceutical industry, etc.), miniaturization of capillary electrophoresis (CE) also is in the focus of interest. CE systems currently represent a major example of use of microfluidic systems. By means of CE technology, substance mixtures of various biomolecules (DNA, proteins, etc.) or inorganic ions can be separated specifically into their components.

To meet the requirements of modern substance research, future lab-on-a-chip systems for CE technology also will have to be suitable for use in high-throughput screening (HTS) and ultra-high-throughput screening (UHTS). It is therefore required to implement microfluidic structures on the standardized format of microtiter plates, with the fabrication on the basis of microtechnically processed polymer substrates being rather inexpensive. For reasons of costs and hygiene, single-use products made of biocompatible polymers offer considerable advantages.

Section snippets

Setup and function of lab-on-a-chip systems for capillary electrophoresis

The setup and functioning principle of a microfluidic system for capillary electrophoresis is represented schematically in Fig. 1. The most simple design of such a system consists of two intersecting microchannels that can be reached via reservoir areas (Fig. 1a). After buffer solution has been introduced into the entire microfluidic CE system, the shorter channel serves as a sample channel for the sample material to enter the area of capillary intersection. This is achieved by means of an

Microtechnical fabrication and assembly

To produce microfluidic modules and systems from polymers, various microtechnical fabrication methods have been made available in the meantime [7]. For the low-cost production of plastic microcomponents, replication methods, e.g. hot embossing, injection molding or injection embossing, are applied [7], [8]. However, this results in the necessity of producing a metal mold insert possessing the inverse microfluidic structures. Depending on the requirements to be fulfilled by the design of the

CE separations in lab-on-a-chip systems

At the end of the separation capillaries, detection can be carried out with light-optical methods (e.g. fluorescence spectroscopy techniques) or with an electric measurement (Fig. 1a). For electric conductivity detection, the measurement electrodes are integrated in the microchannels. In the contactless conductivity detection (CCD technique) mode, they are arranged outside.

The CE systems available (cf. Fig. 7, Fig. 9) may be subjected to simple separation tests of charged particles in an

Summary and outlook

Meanwhile, a large number of microfluidic CE systems have been produced at Forschungszentrum Karlsruhe within the framework of a first prototype series. Using the brass mold inserts available and an optimized vacuum hot embossing technique or injection molding techniques, exact replication of all fluidic CE channel systems in PMMA, PS, and COC was achieved. To obtain real capillary systems, all fluidic microchannel systems are closed in a precise and leakage-free manner. Depending on the

Acknowledgements

The authors would like to thank Messrs. H. Biedermann and A. Mayer (both IMT), D. Scherhaufer (IMVT) for their constant support in the rapid fabrication of the above lab-on-a-chip systems. Thanks go to Dr. H. Hein (IMT) for the fabrication of the mold inserts by UV lithography and nickel electroplating. Thanks are also due to Mr. P. Abaffy (IMT) for the large number of SEMs made as well as for the evaluation of a number of light-optical images to determine the exact channel cross-sections.

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