Novel Dome-Shaped Structures for High-Efficiency Patterning of Individual Microbeads in a Microfluidic Device

摘要

Recently, microfluidic systems have attracted a large amount of interest in various biological-assay applications.[1] Among numerous claims of advantages over conventional methods, short assay times and the low reagent volume required have been well demonstrated and established by researchers. Several papers have published assay times ranging from 30 s to 74 min and many required a volume 10-times less than conventional assays.[2]-[8] In addition, bead-based microfluidic devices possess an edge over normal fluidic systems as it employs microbeads as a solid support. There are three main advantages in the use of these microbeads. Firstly, the surface-to-volume ratio is greatly increased even in a microfluidic device. For example, one gram of microbeads with a diameter of 0.1 m has a total surface area of about 60 m2.[9] As a result, the sensitivity of assays is increased due to higher efficiency of interactions between samples and reagents.[10] Secondly, the analytes attached to the beads can be easily transported in a fluidic system using pressure-driven flow or electric fields. Finally, and most importantly, there are a variety of surface modifications available on these microbeads, which introduce multiple functionalities to a single microfluidic design. Therefore, DNA, RNA, antibodies, antigens, and a vast number of other biological molecules can be easily attached to the microbeads for transport and analysis in a fluidic system.[11]-[15] These added benefits induced by the incorporation of microbeads prompted researchers to devise many different strategies to immobilize beads in microchannels.[16] Andersson et al. fabricated a grid of pillars by deep reactive ion etching to confine the beads for reaction,[17] and Sato et al. constructed a dam for the entrapment of polystyrene beads in an immunosorbent assay.[18] Instead of building physical structures to trap the microbeads, an external magnetic field can be utilized to capture paramagnetic beads in a microfluidic system.[19], [20] Alternatively, the surface of microchannels can be modified by microcontact printing with binding proteins complementary to other proteins attached to the beads.[21] All of the above strategies have similar aims to concentrate the microbeads in a confined area for processing and analysis.