CAREER: Optoelectronic lab-on-a-chip technology for high content automated multiparametric physiological analyses of live cells

In vitro live cells such as stem cells are powerful models to replicate human (patho)physiology and enable detailed analysis of cell function, cellular mechanisms of action, and responses to interventions and therapeutics. The widespread acceptance of these cell models, coupled with their growing commercial availability and ease of deriving patient-specific cells, have underscored their potential to revolutionize our understanding of human physiology and function.

To date, however, limited techniques exist for comprehensive investigation of the properties of such cell models over time, which greatly impedes their translation for physiology investigations, disease modeling, and pharmacology research. This project will address these technical challenges and develop automated lab-on-a-chip platforms for comprehensive chronic monitoring and control of cell physiology.

This will be accomplished via innovations in materials, device fabrication, circuit design, software development, and system integration. The research results represent important steps towards the next generation lab-on-a-chip health monitoring and modulation systems. If successful, the outcomes will significantly simplify the operation, expand the possibilities, and create new opportunities in many programs of biomedical research, in which automated lab-on-a-chip devices with reduced human exposure are highly demanded.

The education activities will integrate with the technical developments through multidisciplinary training of students in bioelectronics research, introduction of new undergraduate courses on optoelectronic biomedical systems. Outreach plans involve lectures and designing pedagogical demonstration kits to educate K-12 students as well as active research participation by local high school students.

This project will develop and validate automated lab-on-a-chip platforms that allow for direct high-content, real-time, multiparametric interrogation of multiple parallel live cell properties and their interplay at meaningful levels of spatiotemporal precision inside standard cell culture environment. The project includes three research objectives: (1) explore cellular-scale components for crosstalk-free electrical recording, stimulation, and triple-parametric fluorescence recording of in vitro live cell function.

The structure-property relationships of those components will be investigated to optimize the device performance. Optical and electrochemical modeling will be performed to yield fundamental insights into their characteristics; (2) develop compact lab-on-a-chip platforms for automated, long-term, multiparametric probing of live cell models under controlled cultivation conditions.

The full compatibility with incubator culturing environment is beneficial for work with dangerous pathogens, such as COVID-19, toxic substances, and radioactivity. Advanced hardware and software designs will enable independent control of each modality, fast measurement, and data analysis. This will eliminate the need of significant technical expertise to manually analyze the high-content data generated, dramatically save the time efforts, reduce error, and improve accuracy for the experimenters; (3) validate the platforms via rigorous benchtop measurements and high-content on-chip screening of induced pluripotent stem cells-derived neurons.

The performance will be benchmarked against commercial systems. The technology and new knowledge in this project will impact the broad biomedical engineering community, including elucidating disease mechanisms, drug testing, personalized medicine, organs-on-chip.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.