Research Program
Biomolecular Devices and Analysis

Objectives

The objective of this project is to develop microfabricated devices capable of performing a reliable and multiplex RNA aptamer selection based on an automated and large-scale analysis of multiplex protein composition. RNA aptamers are RNA molecules selected in vitro by cycles of selection and amplification, a process called SELEX (Systematic Evolution of Ligands by Exponential Enrichment) that allows isolation of extremely rare RNAs that have high affinity for a specific protein. We propose to transform the existing conventional SELEX biotechnology to a multiplex SELEX-on-a-chip by combining Micro-Electro-Mechanical Systems (MEMS) and sol-gel chemistry.

Recently, we demonstrated that specific RNA aptamers bind their respective protein targets in sol-gel droplets and can be selectively eluted from specific sol-gel droplets by micro-heating.  Our prototype microfluidic SELEX system improved selection efficiency, reducing the number of selection cycles needed to produce high-affinity aptamers by as much as 50% when compared directly to conventional filter-binding SELEX. Moreover, using this microfluidic SELEX with TATA Binding Protein (TBP) as a target, we selected aptamers that bind tightly and specifically to this protein that were identical or homologous to those isolated in a previous conventional SELEX, using only half the number of SELEX cycles. In the coming year, we propose to develop this technology into a functioning multiplex system for highly efficient, large-scale, aptamer selections.