A modular microfluidic architecture for integrated biochemical analysis

Abstract

Microfluidic laboratory-on-a-chip (LOC) systems based on a modular architecture are presented. The architecture is conceptualized on two levels: a single-chip level and a multiple-chip module (MCM) system level. At the individual chip level, a multilayer approach segregates components belonging to two fundamental categories: passive fluidic components (channels and reaction chambers) and active electromechanical control structures (sensors and actuators). This distinction is explicitly made to simplify the development process and minimize cost. Components belonging to these two categories are built separately on different physical layers and can communicate fluidically via cross-layer interconnects. The chip that hosts the electromechanical control structures is called the microfluidic breadboard (FBB). A single LOC module is constructed by attaching a chip comprised of a custom arrangement of fluid routing channels and reactors (passive chip) to the FBB. Many different LOC functions can be achieved by using different passive chips on an FBB with a standard resource configuration. Multiple modules can be interconnected to form a larger LOC system (MCM level). We demonstrated the utility of this architecture by developing systems for two separate biochemical applications: one for detection of protein markers of cancer and another for detection of metal ions. In the first case, free prostate-specific antigen was detected at 500 aM concentration by using a nanoparticle-based bio-bar-code protocol on a parallel MCM system. In the second case, we used a DNAzyme-based biosensor to identify the presence of Pb 2؉ (lead) at a sensitivity of 500 nM in <1 nl of solution.laboratory-on-a-chip ͉ microfluidic breadboard ͉ polydimethylsiloxane

Magnetic microsphere-based mixers for microdroplets

“…Thus, dropletbased microfluidic systems offer a promising platform for massively parallel DNA analysis and real-time molecular detection and recognition. [11][12][13] They also offer the promise of decoupling a binary yes/no response from the determination of agent concentration. 9 Rapid mixing is essential in many microfluidic systems for proper biochemical analysis, 13 sequencing or synthesis of nucleic acids, 14 and for reproducible biological processes that involve cell activation, 15 enzyme reactions, 16 and protein folding.…”

“…[11][12][13] They also offer the promise of decoupling a binary yes/no response from the determination of agent concentration. 9 Rapid mixing is essential in many microfluidic systems for proper biochemical analysis, 13 sequencing or synthesis of nucleic acids, 14 and for reproducible biological processes that involve cell activation, 15 enzyme reactions, 16 and protein folding. 17 However, at this small length scale, species transport in fluid flow is dominated by molecular diffusion, which is usually very slow in comparison with the flow residence time.…”

Detection of HIV-1 P24 Gag in Plasma by a Nanoparticle-Based Bio-Barcode-Amplification Method

“…Technological advances in nanotechnology provide the opportunity to overcome many shortcomings of other diagnostic approaches [22][23][24][25]. The nanoparticle-based bio-barcodeamplification method offers an innovative approach to protein detection.…”

Microfluidic parallel circuit for measurement of hydraulic resistance

“…This approach to define a channel segment with complex patterns will be practical for design of microchannel networks that an equivalent electrical circuit model is commonly used. Most importantly, this method will be helpful to develop modular microfluidic systems 26,27 that require precise characterization of each channel module. As a means to characterize the newly developed channel segment with predefined standard channels, this method can provide practical design parameters that facilitate design of microfluidic networks.…”