The capability to sort, that is, to separate and isolate particular molecules, viruses, bacteria and mammalian cells, from a large background of complex mixtures, at very high throughput, purity and efficiency is a key biotechnological capability. Such bioseparation technologies have very broad applications ranging from molecular diagnositics to transplant therapies. Currently, widely used methods for cell sorting include fluorescence-activated cell sorting (FACS) and magnetic activated cell sorting (MACS). Unfortunately, neither of the technologies are well suited for ultrahigh performance cell sorting in a portable and disposable platform. The goal of our research area is to develop electrokinetic and magnetophoretic separation systems that that operate in a massively parallel manner such that unprecedented levels of throughput, purity, and rare cell recovery can be achieved simultaneously. 

 

The invention of hybridoma monoclonal antibody (mAb) technology in 1975 opened the paradigm of affinity reagents which bind specifically to their target molecules. Since then, affinity reagents have become the cornerstone of modern biotechnology, and it is almost inconceivable to imagine an area of biology and medicine that do not depend on their affinity and specificity. However, despite significant advances such as bacteriophage and cell surface display, we continue to be limited by the high cost, lengthy development time, limited availability, and often inadequate biochemical properties of affinity reagents for many applications. This rings especially true in advanced diagnostic and proteomic applications, where the demand for new reagents far exceeds the rate at which they can be produced. Consequently, there remains an urgent need for technologies to identify and produce ligands with high affinity and specificity to particular target molecules quickly, efficiently, reproducibly, and inexpensively. Towards this end, our laboratory develops extremely rapid screening technologies to select and evolve nucleic acid based (aptamers) and peptide based molecules using novel microfluidics technology.

Over the last few decades, the development of effective biosensors received much attention. The technical challenges lie in the fact that, for example, as few as 50 cells of E. coli O157:H7 is sufficient to cause infections, however, these 50 cells may be diluted in a large volume of complex, background mixtures. As a consequence, the current capability to detect pathogens at extremely low concentrations remains limited due to the fact that the biosensors must meet the competing requirements of extremely high sensitivity and exquisite specificity, concurrently. The research in our laboratory focuses on an alternative and complimentary solution to this problem; instead of solely improving the sensitivity or specificity of the biosensor chemistry, we utilize microfabrication technologies to integrate electrokinetic and magnetophoretic enrichment of the analytes with sequence specific biosensors in a microfluidic platform.