Development of a Plasmonic On-Chip System to Characterize Changes from External Perturbations in Cardiomyocytes

Authors

Maedeh Mozneb, Florida International UniversityFollow

Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Biomedical Engineering

First Advisor's Name

Anthony J. McGoron

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Jin He

Second Advisor's Committee Title

Committee Chair

Third Advisor's Name

Sharan Ramaswamy

Third Advisor's Committee Title

Committee Member

Fourth Advisor's Name

Joshua Hutcheson

Fourth Advisor's Committee Title

Committee Member

Fifth Advisor's Name

Shuliang Jiao

Fifth Advisor's Committee Title

Committee Member

Sixth Advisor's Name

Gerard L. Coté

Sixth Advisor's Committee Title

Committee Member

Keywords

Plasmonic Sensors, Heart-on-a-chip, Cardiac Electrophysiology, ion channels, Biosignal Processing

Date of Defense

3-16-2022

Abstract

Today’s heart-on-a-chip devices are hoped to be the state-of-the-art cell and tissue characterizing tool, in clinically applicable regenerative medicine and cardiac tissue engineering. Due to the coupled electromechanical activity of cardiomyocytes (CM), a comprehensive heart-on-a-chip device as a cell characterizing tool must encompass the capability to quantify cellular contractility, conductivity, excitability, and rhythmicity. This dissertation focuses on developing a successful and statistically relevant surface plasmon resonance (SPR) biosensor for simultaneous recording of neonatal rat cardiomyocytes’ electrophysiological profile and mechanical motion under normal and perturbed conditions. The surface plasmon resonance technique can quantify (1) molecular binding onto a metal film, (2) bulk refractive index changes of the medium near (nm) the metal film, and (3) dielectric property changes of the metal film. We used thin gold metal films (also called chips) as our plasmonic sensor and obtained a periodic signal from spontaneously contracting CMs on the chip. Furthermore, we took advantage of a microfluidic module for controlled drug delivery to CMs on-chip, inhibiting and promoting their signaling pathways under dynamic flow. We identified that ionic channel activity of each contraction period of a live CM syncytium on a gold metal sensor would account for the non-specific ion adsorption onto the metal surface in a periodic manner. Moreover, the contraction of cardiomyocytes following their ion channel activity displaces the medium, changing its bulk refractive index near the metal surface. Hence, the real-time electromechanical activity of CMs using SPR sensors may be extracted as a time series we call the Plasmonic Cardio-Eukaryography Signal (P-CeG). The P-CeG signal render opportunities, where state-of-the-art heart-on-a-chip device complexities may subside to a simpler, faster and cheaper platform for label-free, non-invasive, and high throughput cellular characterization.

Identifier

FIDC010529

ORCID

https://orcid.org/ 0000-0003-3472-3859

Previously Published In

Mozneb, M. & Mirza, A. Non-Invasive Plasmonic Based Real-Time Characterization of Cardiac Drugs on Cardiomyocytes Functional Behavior. (2019) doi:10.1021/acs.analchem.9b04956.

Recommended Citation

Mozneb, Maedeh, "Development of a Plasmonic On-Chip System to Characterize Changes from External Perturbations in Cardiomyocytes" (2022). FIU Electronic Theses and Dissertations. 4990.
https://digitalcommons.fiu.edu/etd/4990