Microarrays and microfluidic devices: miniaturized systems for biological analysis

https://doi.org/10.1016/S0167-9317(02)00458-6Get rights and content

Abstract

Nowadays, the possibility to work on the whole genome in real time is achievable. However, new tools are necessary for high throughput analysis and cost reduction. In such a way, microarrays and lab-on-a-chip systems are going to fulfil these new requirements, including the miniaturization of biological assays as well as the parallelization of analysis. Both sensitivity and reliability of microarray devices are key points for the future. The optical enhancement of the fluorescence signal is particularly addressed in this issue, where it is shown that a significant increase in sensitivity can be reached. Concerning the technology of electrophoresis in microfluidic devices, remarkable developments have been achieved, especially in the DNA separation area. In particular, a specifically designed microfluidic device has been implemented for high throughput genotyping and its stability has been validated on a set of 150 thermally cycled biochemical reactions.

Introduction

The industrial approach of DNA sequencing has allowed the determination of the first draft of the human genome. A 109 increase in the gene mapping efficiency has been achieved during the last 25 years and the same relative increase is necessary to achieve a personalized medicine by the turn of 2030 [1]. Microarrays and lab-on-a-chip systems are adequate tools to fulfil these new requirements, as they include the miniaturization of biological assays as well as the parallelization of analysis. The aim of this paper is to present the state of the art of these technologies and to discuss their actual limitations. Possible improvements are illustrated through the description of results on optical enhancement of microarrays sensitivity. A new design for high throughput genotyping microfluidic device is also presented.

Section snippets

Microarrays principle and technologies

The microarrays technique is based on the mutual selectivity between complementary strands of nucleic acids due to hydrogen bonds leading to a double helix structure as described by Watson and Crick in 1953 [28]. The process of recognition between two single strands of nucleic, called hybridisation, can be highly parallel: every sequence of a complex biological sample can be interrogated simultaneously by an array of single strand nucleic acid probes tethered to a solid support [2]. After a

Optical enhancement of the microarrays sensitivity

As described in Fig. 1, the microarray is made of a substrate, on top of which thin films are deposited. After the hybridization step, each double strand bears one or more fluorophores. By considering each fluorophore as an electromagnetic dipole, we can simulate the fluorescence signal of a microarray [19]. The optical parameters as well the thickness of the thin films corresponding to an enhanced and optimized signal can be simulated whatever the substrate is. As the most critical application

Microfluidic devices

An ideal microfluidic system corresponds to a complete miniaturization of analytical equipments. The user would still have to collect a biological sample, but once introduced into the microsystem, all subsequent analytical steps would be performed automatically from sample separation to analytical results. Although the concept has been performed by miniaturizing the analytical equipments, the technology comes from the microelectromechanical and microelectronics industries [20].

As the critical

Continuous flow analytical microsystem

The genotyping allows the characterization of DNA genetic variation between individuals (genotype) as well as the study of transmission pathway within families. The correlation between these information and illnesses is necessary for the development of new therapeutic approaches. The study of the single nucleotide polymorphism (SNP) is crucial for characterizing molecular targets. The typical requirements for an integrated genotyping device are throughput (1 000 000 genotypes/day), reaction

Conclusion

Microarrays and microfluidic devices are critical tools for the post genomic era to unravel the function of thousand genes in a massively fashion. Microarray technology is rapidly advancing and applications ranging from genetic testing to gene expression as well as drug discovery have been demonstrated. Commercially available glass slides typically includes 25 000 genes sequences on a 3×1 in. area (1 in.=2.54 cm). However, reliability and sensitivity have still to be improved. There is room for

Acknowledgments

The authors are indebted to the people involved in this work from the different CEA divisions: Life Science, Materials and Science, Microtechnology, Optronics, Systems for Information and Health and Nuclear Division. This work was supported financially by the French ministry of Industry in a cooperation program with Genset.

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