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

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

An Ultra-Sensitive Sol-Gel Biocomposite Electrode Sensor for Cyanide Detection

Cyanide is a widely used industrial chemical but is also very toxic. Cyanide binds strongly with hemoglobin than that of oxygen which causes histoxic hypoxia, if it is introduced into the bloodstream. This pairing reaction can thus be exploided for the development of a cyanide detection sensor. Our research group has been developing a sensor platform that can utilize different enzymatic couplings for the detections of metabolites and species that are of health and environmental concerns at extremely low concentrations. In this study, we report the detection of cyanide using our sensor platform with a biocomposite layer made up of polymers, nanogold sol-gel, and hemoglobin. The biocomposite is coated on the surface of anchoring materials such as Au, Pt, and glass carbon electrode. This ultra high sensitive biosensor can detect cyanide at concentration levels orders of magnitude lower than any reports found in the public domain. This report reveals results in twofold: at low concentration levels above 1´10-5 M and ultra-low levels of 1´10-18 M. These two concentration ranges represent applications for rountine cyanide monitoring and research exploration. We will also discuss factors that affect the sensitivity, interference, durability, and performance enhancement of this sensor. Due to its ability to detect cyanide at such wide range of concentrations, this cyanide sensor can have unique applications in homeland security, biomedical, and environmental monitoring

Microfluidic Organ-Chips and Stem Cell Models in the Fight Against COVID-19

SARS-CoV-2, the virus underlying COVID-19, has now been recognized to cause multiorgan disease with a systemic effect on the host. To effectively combat SARS-CoV-2 and the subsequent development of COVID-19, it is critical to detect, monitor, and model viral pathogenesis. In this review, we discuss recent advancements in microfluidics, organ-on-a-chip, and human stem cell-derived models to study SARS-CoV-2 infection in the physiological organ microenvironment, together with their limitations. Microfluidic-based detection methods have greatly enhanced the rapidity, accessibility, and sensitivity of viral detection from patient samples. Engineered organ-on-a-chip models that recapitulate in vivo physiology have been developed for many organ systems to study viral pathology. Human stem cell-derived models have been utilized not only to model viral tropism and pathogenesis in a physiologically relevant context but also to screen for effective therapeutic compounds. The combination of all these platforms, along with future advancements, may aid to identify potential targets and develop novel strategies to counteract COVID-19 pathogenesis