Micro and Nanoengineering Approaches for Advancing Biomedical Applications of Aptamers

Seminar Guest: Qiao Lin, Department of Mechanical Engineering, Columbia University

Abstract:

Aptamers are short, single-stranded nucleic acid sequences that can bind specifically to biological targets. Compared to other affinity molecules such as antibodies, aptamers are attractive due to their applicability to a broad range of targets, customizability for controlled binding characteristics, ease of conjugation with other molecules, small size and potentially low immunogenicity, and synthetic availability with minimal batch-to-batch variability and at low cost.

In this presentation, we will describe the combination of aptamers with functional nanomaterials to enable innovative nanobiosensing. Specifically, we will focus on affinity nanobiosensors that use aptamer-functionalized monolayer graphene. The specific binding of aptamers with target biomarkers can induce a change in the carrier concentration of the graphene in a field-effect transistor configuration, which can be measured for the sensitive and specific determination of biomarker concentrations. These graphene nanosensors can be surface-modified to reject the interference of nonspecific background molecules in physiological fluids such as serum and dialytic ultrafiltrates, and can operate in differential form to reject variations in environmental conditions. Fabricated on highly flexible polymer substrates, the nanosensors can also conform to underlying surfaces in wearable and implantable applications with improved reliability and biocompatibility.

The second part of the presentation will focus on the rapid and efficient generation of aptamers. Traditionally, aptamer generation is time-consuming and laborious. Microfluidic technology, by physical and process integration and automation, can enable more efficient and rapid aptamer discovery. We show that the process, known as SELEX, for evolutionary enrichment of target-binding nucleic acid sequences can be completed in a microfluidic device within several hours, compared to up to a month required by conventional platforms. Using this technology, we have obtained DNA aptamers that specifically recognize glycans and glycosylated peptides for biomarker identification, and monoclonal antibodies from individual patients for personalized monitoring of minimal residual disease in multiple myeloma.

The advancements in aptamer-based nanobiosensing and microfluidic generation of aptamers represent a promising initial step towards the broader use of aptamers as versatile affinity reagents for early disease detection, and for personalized and more effective disease monitoring and treatment.

Bio: Qiao Lin is a professor in the Mechanical Engineering Department at Columbia University. He received the Ph.D. degree in robotics from Caltech in 1998, where he also conducted postdoctoral work on microelectromechanical systems (MEMS). He was on the Mechanical Engineering faculty at Carnegie Mellon from 2000 to 2005. Professor Lin has been directing the Columbia BioMEMS Laboratory since 2005. His research centers on micro- and nanoscale devices as applied to biological sensing and manipulation, with an emphasis on controlling, sensing and characterizing biological systems by integrating MEMS transducers with microfluidic capabilities. Specific research thrusts in his laboratory include micro- and nanobiosensors, aptamer-based microfluidic systems, and microfluidic manipulation and control of biomolecules and cells.