impedance spectroscopy; CMOS biosensor; body-on-a-chip; 3D microtissue; electrochemical sensing; Hanging-drop; electrophysiology recording
Bounik Raziyeh, Dragas Jelena, Radivojevic Milos, Geissler Sydney, Sitnikov Sergey, Muller Jan, Hierlemann Andreas, Shadmani Amir, Viswam Vijay, Chen Yihui (2019), Stimulation and Artifact-suppression Techniques for in-vitro High-density Microelectrode Array Systems, in IEEE Transactions on Biomedical Engineering
BounikRaziyeh, ShadmaniAmir, DragasJelena, Urwyler Cedar, Boosjulia, ObienMarie, Müller Jan, ChenYihui, Hierlemann Andreas, Viswam Vijay (2018), Impedance Spectroscopy and Electrophysiological Imaging of Cells With a High-Density CMOS Microelectrode Array System, in IEEE Transactions on Biomedical Circuits and Systems
, 12(6), 1356-1368.
BounikRaziyeh, GusmaroliMassimiliano, ViswamVijay, ModenaMario, HierlemannAndreas (2018), COMSOL modeling of an integrated impedance sensor in a hanging-drop platform
, Frontiers in Cellular Neuroscience, Frontiers in Cellular Neuroscience.
BounikRaziyeh, GusmaroliMassimiliano, MisunPatrick, ViswamVijay, HierlemannAndreas, ModenaMario, Integration of Discrete Sensors and Microelectrode Arrays into Open Microfluidic Hanging-Drop Networks, in IEEE International Conference on Micro Electro Mechanical Systems,
, IEEE , IEEE.
Traditional dish-based, two-dimensional (2D) cell cultures have limited prediction capability for drug testing, whereas three-dimensional (3D) spherical microtissues (spheroids) much more accurately replicate physiological conditions of cells in the respective tissue. Such spheroids can be formed and cultured in microphysiological multi-tissue formats (“body-on-a-chip”) by using the hanging-drop technology recently developed at the Hierlemann Group, ETHZ. However, there is a lack of accurate and 3D-tissue-compatible online sensor and read-out methods for assessing tissue responses to, e.g., administration of drugs or changes in environmental parameters. Therefore, the central aim of this proposal includes (i) the development of a multifunctional CMOS sensor system chip that includes impedance spectroscopy, electrochemical sensing, and electrophysiology modules along with a custom designed multipurpose electrode arrangement on a single chip, and (ii) the integration of the CMOS chip into the hanging droplet platform, where the chip functional units will be used according to application needs: impedance data will be used for microtissue growth profiling, electrochemical data will be used for tracking lactate production by, e.g., a tumor spheroid, and electrophysiological measurements will be performed to follow the beating activity of cardiac spheroids. The use of IC technology also enables the realization of signal amplification, filtering, digitization, data storage and transmission units on the same chip. The initial phase of the project will include the design of the CMOS circuits in 180nm IC technology according to the application specifications. After chip fabrication by the XFab foundry (Erfurt, Germany), post-processing, chip functionalization, and microfluidic integration will be carried out in-house at D-BSSE, ETHZ. The device will be functionally tested and validated by using human cardio-myocyte, liver, or tumor spheroids. The functionality of the novel overall platform will be assessed by dosage of drugs, such as isoprotenerol.