(15i) Point-of-Care Molecular Detection with Surface Engineering of Nanomaterials for Diagnostic Platforms

Authors: 
Mahshid, S. S., University of Toronto
Research Interests:

A fundamental axiom of medicine is that faster diagnosis yields earlier intervention, reducing the spread of infection and improving patient outcomes. The development of effective, point-of-care (POC) methods for the detection of disease biomarkers would thus increase the frequency with which many diseases are detected and identified, and decrease the delay between diagnosis and treatment. In order to be efficient, POC diagnostic devices must put clinically actionable information in a doctorâ??s hands during a patientâ??s first visit rather than during a follow-up. Here we proposed a new signaling mechanism for detection of a variety of molecules that displays clinically relevant sensitivity and specificity for variety of targets, and ideally is: 1-rapid relative to the 15 minutes of a typical patient/provider interaction, 2-selective enough to work in unprocessed bodily fluids, 3-amenable to small volumes rather than venous blood draws, 4-quantitative, and 5-able to diagnose multiple analytes simultaneously. This electrochemical DNA-based sensing platform is designed to detect real antibodies in human blood based on steric hindrance effects of the big molecule to influence the DNA-DNA hybridization. We hypothesized that when a large macromolecule binds to a DNA strand, this should, in principle, reduce the number of DNA strands that can hybridize to their complementary strand attached to a surface. We set out to demonstrate this steric hindrance mechanism using electrochemistry by employing a redox-labeled signaling DNA strand and a gold electrode that contains the complementary capturing DNA sequence at high surface density. Upon binding to the capturing strands, the redox-labeled signaling strands generate a large electrochemical signal by bringing the redox labels close to the electrode surface. In the presence of a large target protein that binds a recognition element on the signaling strand, we hypothesize that fewer copies of this strand will be able to reach the surface-bound capturing strand due to steric hindrance, therefore generating lower electrochemical currents. We eventually demonstrate the multiplexing detection of multiple antibodies within less than 10 minutes in whole blood having this detection platform. Additionally, the platform can be broadly adapted to selectively and specifically detect many other proteins having well-designed recognition ligand to that protein. Thus, this detection platform holds great promise to be well positioned for adaptation as, for example, point-of-care diagnostics.

As a faculty candidate, I envision three potential multidisciplinary projects, which are in line with the interdisciplinary and collaborative research environment: (1) Point-Of-Care diagnosis: Single-step methods for rapid and quantitative diagnosis of disease biomarkers. (2) Electrochemical 2D and 3D -sensors for direct and/or indirect molecular detection. Improvement of the catalytic activity of nanostructured Pt (Pd, or Au) by electrochemical alloying, (3) Development of Giant MagnetoResistnace in nanoscale magnetic Multilayer for biosensing application.

Teaching Interests:

I am eager to continue to the undergraduate and graduate education. I would be exited to teach courses across the curriculum of Materials Engineering, Chemical Engineering, Nanotechnology Engineering and Biomedical Engineering, as well as advanced course subjects in the field of nanobiotechnology, surface engineering, electrochemistry and analytical chemistry.

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