Biosample Preparation by Lab-on-a-Chip Devices

The main objective of this chapter is to review the on-chip molecular sample preparation methods. For an on-chip sample preparation for large biological objects, such as cells and particles, prior to the molecular sample preparation, there are several methods available such as dielectrophoresis, hydrophoretic filtration, and separation via magnetic forces, acoustic forces, and optical forces. These sample preparation methods are taking an increasingly important role in the on-chip sample preparation. However, a detailed description of these methods is beyond the scope of this review and the interested readers are referred to other review papers on this topic [2-5]. Typically, most biosensing involves detection of low-concentration target molecules over molecular backgrounds with much higher concentrations. In genomic biosensing, this problem is largely resolved by , which can be used to increase the number of polymerase chain reaction (PCR) nucleotides with a specific sequence by several orders of magnitudes. However, in proteomic biosensing and bioanalysis, the issue of sample preparation still remains as a serious technical bottleneck, since there is no PCR equivalent for proteins and other biomolecules. For example, blood plasma or serum from any source is valuable for proteomics-based discovery of biomarkers for diseases or for discovery of novel drug targets. Detection of these proteins has potential diagnostic values; however, the major challenge is the complexity of common biomolecule samples. It is estimated that there are more than 10 000 present in a serum sample. Moreover, most biomarker proteins are generally protein species present at very low concentrations (< pg/ml), while others, such as albumin and , are present in very immunoglobulins large amounts ( > mg/ml). This large concentration variation poses a formidable challenge to currently existing techniques, most of which do not have low enough and large enough dynamic biomolecule detection detection sensitivity range. It is expected, therefore, that the detection of low-abundance protein species or biomarkers would be possible only by better sample preparation and sorting. Conventionally, two dimensional (2D) protein gel electrophoresis, coupled with mass spectrometry (MS) has been the norm of proteomics research for decades, while multidimensional liquid chromatography coupled with MS is getting wider use due to ease of automation. Both techniques demonstrate similar separation peak capacity (up to ∼3000) and dynamic range of detection (∼10 ) when coupled with MS. 4