Grant: Discovery Grants Program - Individual
York University
$121,000.00
Disruptive Analytical Technologies for Biomedical Sciences
FY 2023-24
Summary
My research program is mainly concerned with the development of disruptive analytical technologies for biomedical sciences. Modern biomedical sciences require accurate tools for studying biomolecular interactions and molecular markers of cellular processes. They also require effective tools for generation of affinity ligands for protein targets. Current technological paradigms limit accuracy and effectiveness of tools that are based upon them. Our mission is to establish new paradigms and develop game-changing technologies upon them. We currently focus on shifting three paradigms. First, we aim to make the solution-based approach dominate over the surface-based approach in kinetic characterization of biomolecular interactions and selection of affinity ligands. Second, we work towards replacing arbitrary characteristics of reactions with non-arbitrary ones (reaction rate constants) when characterizing catalytic processes in individual cells. Third, we aim to augment liquid-liquid extraction with molecular stream separation in continuous-flow chemistry. Over the past 6 years, we have developed a number of highly-enabling analytical tools based on this foundation: (i) accurate constant via transient incomplete separation for Kd measurements of protein-small molecule complexes (Angew Chem Int Ed 2019, 58, 6635), (ii) ideal-filter capillary electrophoresis for single-round selection of aptamers (Angew Chem Int Ed 2019, 58, 2739), (iii) cytometry of reaction rate constant for studying cross-membrane transport (Anal Chem 2019, 91, 4186), (iv) highly-sensitive quantitative detection of multiple microRNAs in complex biological matrices (Anal Chem 2020, 92, 14251), and (v) non-aqueous continuous-flow electrophoresis for combination with continuous-flow organic synthesis (Lab Chip 2019, 19, 2156). Forty trainees have been trained, and the results of their work were published in 60 papers cited 1200 times. In the next 5 years, we will continue building novel technologies based on our three paradigms. We also plan to continue our curiosity driven exploratory/discovery research. One direction for such research is artificial intelligence and machine learning in bioanalytical technologies. Our NSERC Discovery research will remain highly interdisciplinary ranging from chemistry to biology and from physics to mathematics. Many projects will be carried out in collaboration with other academic laboratories and R&D companies. Ten graduate students in 3 programs (chemistry, biology, and physics) and 2 PDFs will be trained on a continuing basis. We anticipate that the results of our basic research will create new knowledge in analytical chemistry, physical chemistry, molecular biology, and other fields of study. We also expect that our application-driven research will provide biomedical and pharmaceutical companies with new R&D tools required for creation of new rapid and sensitive diagnostics and more effective treatments for complex diseases, such as cancer.
Program
Discovery Grants Program - Individual
Recipient
Location
Ontario, Canada
Recipient Type
Academia
Type
Grant
Source
NSERC's Awards Data
As published
Application id
RGPIN-2022-04563
Name nom
Krylov, Sergey
Department département
Department of Chemistry
Organization id
38
Institution établissement
York University
Province en
Ontario
Province fr
Ontario
Country en
CANADA
Country fr
CANADA
Fiscal year exercice financier
2023
Competition year année de concours
2022
Award amount
121000
Program id
RGPIN
Program name en
Discovery Grants Program - Individual
Program name fr
Programme de subventions à la découverte - individuelles
Group en
DISCOVERY RESEARCH
Group fr
RECHERCHE AXÉE SUR LA DÉCOUVERTE
Committee code
1504
Committee name en
Chemistry
Committee name fr
Chimie
Area of application code
1201
Area of application group en
Advancement of knowledge
Area of application group fr
Avancement des connaissances
Area of application en
Life sciences (including biotechnology)
Area of application fr
Sciences de la vie (y compris biotechnologie)
Research subject code
3503
Research subject group en
Analytical chemistry
Research subject group fr
Separation methods
Research subject en
Chimie analytique
Research subject fr
Méthodes de séparation
Application title
Disruptive Analytical Technologies for Biomedical Sciences
Keyword
Affinity interactions; Analysis of chemical reactions in single cell; Aptamers and DNA-encoded libraries; Continuous separation in continuous-flow chemistry; Disruptive technologies for rapid diagnostics of diseases; Quantitative analysis of multiple RNAs in biological matrix; Selection and characterization of affinity probs
Application summary
My research program is mainly concerned with the development of disruptive analytical technologies for biomedical sciences. Modern biomedical sciences require accurate tools for studying biomolecular interactions and molecular markers of cellular processes. They also require effective tools for generation of affinity ligands for protein targets. Current technological paradigms limit accuracy and effectiveness of tools that are based upon them. Our mission is to establish new paradigms and develop game-changing technologies upon them. We currently focus on shifting three paradigms. First, we aim to make the solution-based approach dominate over the surface-based approach in kinetic characterization of biomolecular interactions and selection of affinity ligands. Second, we work towards replacing arbitrary characteristics of reactions with non-arbitrary ones (reaction rate constants) when characterizing catalytic processes in individual cells. Third, we aim to augment liquid-liquid extraction with molecular stream separation in continuous-flow chemistry. Over the past 6 years, we have developed a number of highly-enabling analytical tools based on this foundation: (i) accurate constant via transient incomplete separation for Kd measurements of protein-small molecule complexes (Angew Chem Int Ed 2019, 58, 6635), (ii) ideal-filter capillary electrophoresis for single-round selection of aptamers (Angew Chem Int Ed 2019, 58, 2739), (iii) cytometry of reaction rate constant for studying cross-membrane transport (Anal Chem 2019, 91, 4186), (iv) highly-sensitive quantitative detection of multiple microRNAs in complex biological matrices (Anal Chem 2020, 92, 14251), and (v) non-aqueous continuous-flow electrophoresis for combination with continuous-flow organic synthesis (Lab Chip 2019, 19, 2156). Forty trainees have been trained, and the results of their work were published in 60 papers cited 1200 times. In the next 5 years, we will continue building novel technologies based on our three paradigms. We also plan to continue our curiosity driven exploratory/discovery research. One direction for such research is artificial intelligence and machine learning in bioanalytical technologies. Our NSERC Discovery research will remain highly interdisciplinary ranging from chemistry to biology and from physics to mathematics. Many projects will be carried out in collaboration with other academic laboratories and R&D companies. Ten graduate students in 3 programs (chemistry, biology, and physics) and 2 PDFs will be trained on a continuing basis. We anticipate that the results of our basic research will create new knowledge in analytical chemistry, physical chemistry, molecular biology, and other fields of study. We also expect that our application-driven research will provide biomedical and pharmaceutical companies with new R&D tools required for creation of new rapid and sensitive diagnostics and more effective treatments for complex diseases, such as cancer.