Nuwan Bandara

Research Description:

Area of Research: The research in our lab falls under the single-molecule sensing umbrella, wherein we focus not only on the chemistry of sensing but also on the physics, engineering, and electronics aspects of sensing.

What we do: DNA, RNA, proteins, and glycans are imperative building blocks of life. These molecules are omnipresent and responsible for a plethora of biofunctions. Some even serve as biomarkers for health conditions. Our group focuses on real-time sensing of these nanoscale biomolecules to uncover details encompassing structure, function, reaction dynamics, and energy landscapes (to name some) at the molecular level by probing (native, mutated, stimulated, etc.) them individually. We build and develop chemistries, instruments, setups, and codes for this.

Single-Molecule sensing: It's all about detecting one molecule at a time. For this, we use nanopores (and nanopipettes). Nanopores are nanoscale apertures through an otherwise impervious membrane separating two electrolyte reservoirs. A voltage is first applied across the pore, which generates an ionic current through the pore due to ion transport. We call this the open-pore current. Then, the sample containing the target molecule is added to one of the reservoirs and driven across the pore fundamentally via electrophoresis and/or electroosmosis (other mechanisms exist). This perturbs the ion movement across the nanopore and generates ionic signatures (mostly resistive, akin to a square waveform) characteristic of the translocating analyte. For example, the longer the analyte, the longer the duration of this perturbation, and the larger the cross-sectional diameter of the analyte, the larger the magnitude of this current perturbation. We call these perturbations events.

What can events tell us? A lot is the most straightforward answer. For example, information about structure and function, either native, mutated, or in response to (external or internal) stimuli, can be observed in real-time. As incredible as the technology sounds, it is not without limitations. For example, but not limited to, premature pore failure, lack of selectivity, relatively high setup cost, poor SNR and throughput in low-electrolyte conditions, and high pM (or low nM) limit of detection impede the progression of the technology. We aim to find solutions to these (legacy) issues to propel solid-state nanopore technology to its rightful place in the single-molecule realma reliable, low-cost, rapid, selective, ultra-sensitive, easy-to-operate, and accessible technology!

Electronics: We are avid fans of microcontroller technology and its capability to provide low-cost yet robust solutions to create accessible technologies. Within this space, we develop in-house devices for single-molecule sensing efforts. If you are a microcontroller enthusiast (or hobbyist), we'd like to hear from you!

Coding: We like to code our solutions in MATLAB, Mathematica, Python, and LabView (the list will grow over time). Some experiments require the synergistic communication of multiple instruments: we make interfaces to make this possible. Furthermore, nanopore experiments can yield tens to hundreds of GBs of data: we create highly efficient analysis platforms to analyze such heavy data sets!

We aim to give our students a broader research experience spanning chemistry, (bio)physics, engineering, electronics, and coding.