(7af) Nano-Bio-Sensors for Point-of-Care Diagnostics

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

Development of rapid approaches for in-situ and real-time monitoring of analytes in complex matrices plays crucial roles in medical diagnostics, prognostics and therapeutics. Current methods for quantitative detection of disease markers, such as ELISAs, Western blots, fluorescence polarization assays, are time-consuming and multiple-step processes reliant on well-trained technicians working in fully-equipped laboratories. Inspired by electrochemical approaches I have invented an electrochemical DNA-based single-step detection mechanism (eSHHA) for rapid quantitative detection of proteins and small molecules in therapeutic ranges. This platform, based on steric hindrance effects at the nanoscale, has capability of integration with various sensor devices aiming for detection of variety of target molecules, including DNAs/RNAs, proteins/antigens biomarkers and pathogens. I engineered the sensor’s surface by immobilization of selecting/capturing monolayers (DNAs) on the interface of the sensing electrode to provide the desired specificity in real biological samples, e.g. whole blood.

On the other hand, I have achieved high sensitivities in these sensing systems through utilizing electrochemical detectors with nanostructured electrodes in macroscale and microscale. In this regard, the improvement in sensor’s selectivity is achieved through the impact of nanoroughness on the thermodynamics of surface reactions. Also, the high curvature on the nanostructures is advantageous for the display of capturing monolayer on the surface with nanoscale roughness. This provides low detection limits for the sensors down to picomolar and femtomolar. Plus, these nanostructured electrodes enhance the speed of detection mechanism by their macroscopically sized electrodes that overcomes the limitations of diffusive transport impeding the performance of nano-sized sensors.

Finally I developed on chip diagnostic platforms based on integrating DNA-based single-step detection mechanism with nanostructured electrodes and microelectronic chips. The microelectronic chips provide addressable electrodes for ease of multiplexity. I adapted these sensor platforms for translational applications such as (1) at-line monitoring of signaling proteins in stem cell regeneration, (2) real-time monitoring of small digoxin drug molecules in their therapeutic ranges and (3) rapid diagnosis of HIV through quantitative detection of anti-HIV antibodies directly in patient samples.

Research Experience:

My translational research integrates materials science and engineering, biochemistry and biomedical engineering to develop solutions in health care (diagnostics and therapeutics) and environment (biological and chemical sensing). The last ten years of my research was focused on (1) synthesis, characterization, modification and implementation of nanostructured materials, (2) enzyme-based, electrocatalytic-based, and affinity-based nanoscale molecular detection (biomarkers and chemicals) and (3) design and fabrication of inexpensive microbiochips for mobile sensing devices.

Future Direction:

As a faculty, I envision three potential projects, which are in line with interdisciplinary and collaborative research environments: (1) Point-of-care diagnostics: Single-step methods for rapid and quantitative detection of biomarkers using affinity-based sensors (2) Online monitoring of interfering analytes and contaminants in ex-vivo expansion process of stem cells for the future of regenerative medicine (3) Magnetic nanostructured-electrodes for high-efficiency concentration and capturing of target biomarker.

Selected Publications:

  1. Sahar Sadat Mahshid, Francesco Ricci, Shana O. Kelley, Alexis Vallée-Bélisle, “An Electrochemical DNA-based Immunoassay that Employs Steric Hindrance to Detect Small Molecules Directly in Whole Blood”, ACS Sensors, 2 (2017), 718−723.

  2. Sahar Sadat Mahshid, Sébastien Camiré, Francesco Ricci, Alexis Vallée-Bélisle, “A Highly Selective Electrochemical DNA-Based Sensor That Employs Steric Hindrance Effects to Detect Proteins Directly in Whole Blood’’, Journal of American Chemical Society, 137 (2015), 15596–15599. [Impact factor 13.038]

  3. Sahar Sadat Mahshid, Sara Mahshid, A. Dolati, M. Ghorbani, L. Yang, Sh. Luo, and Q. Cai, “Electrodeposition and electrocatalytic properties of Pt/Ni–Co nanowires for non-enzymatic glucose detection”, Journal of Alloys and Compounds, 554, 2013, 169–176. [Impact factor 3.15]

  4. Wendi Zhou, Sahar Sadat Mahshid, Weijia Wang, Alexis Vallée-Bélisle, Peter W. Zandstra, Edward H. Sargent, and Shana O. Kelley, “A Steric Hindrance Assay for Secreted Factors in Stem Cell Culture”, ACS Sensors, 2 (2017), 495−500.

  5. Phil De Luna, Sahar Sadat Mahshid, Jagotamoy Das, Binquan Luan, Edward H. Sargent, Shana O. Kelley, and Ruhong Zhou, “High-Curvature Nanostructuring Enhances Probe Display for Biomolecular Detection”, Nano Letters, 17 (2017), 1289−1295. [Impact factor 13.779]

  6. Sara Mahshid, Adam H. Mepham, Sahar Sadat Mahshid, Ian B. Burgess, Tina S. Safaei, Edward H. Sargent, Shana O. Kelley “Mechanistic Control of the Growth of Three-Dimensional Gold Sensors”, The Journal of Physical Chemistry C, 120 (37), 2016, 21123–21132 [Impact factor 4.5]

  7. Tina Saberi Safaei, Jagotamoy Das, Sahar Sadat Mahshid, Peter M. Aldridge, Edward H. Sargent, Shana O. Kelley, “Image-Reversal Soft Lithography: Fabrication of Ultrasensitive Biomolecular Detectors’’, Advanced Healthcare Materials, 5 (2016), 893 – 899. [Impact factor 5.79]

Teaching Interests:

I have gained teaching experience at different levels in academia. During my graduate studies I delivered lectures, administered laboratory activities and co-supervised Master’s students. At Sharif University of Technology, as a teaching assistant I planned, and conducted undergraduate courses and laboratory sessions. My teaching philosophy is based on promoting active learning strategies in engineering. At U de M and U of T, I directly supervised undergraduate and graduate students in research projects. I initiated their projects, hiring and training to successful transition to research. I believe my experience in different academics environments of Iran, China and Canada would help me contribute to the advancement of student success across individual identities, racial/ethnic categories, social and economic backgrounds.