This NSF award by the Biosensing /CBET program supports work by Professor Zhang at Boston University to pursue biological/biochemical sensing at cellular and even finer levels by converting a biological response to an electrical signal using micro/nanosystems and further implementing an impedance-based real-time assay system for high-throughput screening (HTS). The objective of this research is to design and test a multidisciplinary micro/nanosystem for positioning individual cells into an analyzing matrix for real-time monitoring cell viability and response with a miniaturized HTS system. In the proposed micro/nanosystem, existing electrical cell-substrate impedance sensing (ECIS) techniques will be modified for single cell monitoring. In order to broaden range of usable cell types, electrochemical impedance spectroscopy (EIS) will be employed to characterize cell electrical properties and a cell-free system. To precisely position individual cells to correctly sized working electrodes, alternating current electrokinetics (ac EK) will be exploited and integrated into the proposed micro/nanosystem.
The development of highly sensitive, yet simple and robust impedance-based biosensors, integrated into a miniaturized system will enable real-time high-throughput study of single cells, best monitoring living cells to observe, characterize, and model functional behavior at the cellular and even finer levels so as to explore biosensor specificity and flexibility for distinct responses to different combinations of stimuli, making an impact on fields ranging from biosenisng/bioinstrumentation to micro/nanosystems with applications to the biomedical, environmental, and security needs. Educationally, this program will impact a diverse student population through merging biosensing and engineering education research to train the next generation of scientific/engineering leaders.
This NSF award by the Biosensing/CBET program supports work by Professor Zhang at Boston University to pursue biological/biochemical sensing at cellular and even finer levels by converting a biological response to an electrical signal using micro/nanosystems and further implementing an impedance-based real-time assay system for high-throughput screening (HTS). The objective of this research is to design and test a multidisciplinary micro/nanosystem for positioning individual cells into an analyzing matrix for real-time monitoring cell viability and response with a miniaturized HTS system. This project has implemented and disseminated an educational and training program that develops interdisciplinary modes of thought at the boundary of science and engineering through integrated research opportunities in micro/nanosystems. The project incorporates undergraduate and graduate research, graduate education at Boston University and also outreach to high-school students. The significant contribution of this work entails following aspects: 1) Development of impedance sensing and analysis to obtain unknown electrical properties of primary cardiomyocyte culture; 2) Development of impedance sensing and analysis for real-time recording of cell adhesion in terms of equivalent cell-substrate distance; 3) The first demonstration of detecting ongoing cardiomyocyte death earlier than Trypan blue exclusion tests; 4) The first demonstration of intervening in cell death processes according to the results of impedance sensing. In the proposed micro/nanosystem, existing electrical cell-substrate impedance sensing (ECIS) techniques are modified for single cell monitoring. In order to broaden range of usable cell types, electrochemical impedance spectroscopy (EIS) is employed to characterize cell electrical properties and a cell-free system. To precisely position individual cells to correctly sized working electrodes, alternating current electrokinetics (ac EK) are exploited and integrated into the proposed micro/nanosystem. The development of highly sensitive, yet simple and robust impedance-based biosensors, integrated into a miniaturized system will enable real-time high-throughput study of single cells, best monitoring living cells to observe, characterize, and model functional behavior at the cellular and even finer levels so as to explore biosensor specificity and flexibility for distinct responses to different combinations of stimuli, making an impact on fields ranging from biosenisng/bioinstrumentation to micro/nanosystems with applications to the biomedical, environmental, and security needs. Given the broad interdisciplinary nature of this research, graduate students have had an outstanding opportunity to work in an area that bridges basic research and application. Graduate student Yiling Qiu received his PhD through fully working on this project with his PhD thesis entitled "Impedance Sensing for Cellular Response Studies". He is now a Staff Scientist at Brigham and Women’s Hospital. Graduate students fully or partially working on the proposed project have also won prestigious awards. In addition, several undergraduate and high-school students were recruited to work on this project through NSF REU, BU UROP, and BU RISE programs. These students have become extremely valuable to the lab and almost indispensable to the key graduate and the project. Independent of their creativities and resourcefulness, they are also trained on almost every machine in labs. In addition, this project has served as an excellent vehicle for the teaching of two contemporary micro/nanosystems courses, both offered by Professor Zhang for industry, through the existing Boston University Distance Learning Program. Boston University has developed a microfluidic bio-impedance assay for real-time, quantitative monitoring of cell responses in exposure to different stimuli. Our vision is to transform the science and engineering community's capacity to probe biological systems at the cellular level by designing, building and testing a new generation of biosensing platforms. There is no doubt that an interdisciplinary approach has a critical role to play in 'spying on cells', by designing and building micro- and nano-scale sensors and instruments needed for multi-dimensional simultaneous data gathering from within and around living cells. The results of this research would thus be wide-open for a transformative research frontier, and may even provide a potential firm foundation for rapid technological innovation that will impact the quality of life.
