A novel microphysiometer based on high sensitivity LAPS and microfluidic system for cellular metabolism study and rapid drug screening.

This study presents a novel microphysiometer for studying the mechanism of cellular metabolism and drug effect. Based on the photocurrent amplification of light-addressable potentiometric sensor (LAPS), the constant voltage detection mode was introduced to enhance the detection sensitivity to replace the conventional constant current mode with the slow feedback rate. The photocurrent amplification of LAPS was improved by developing the sensor structure and fabrication processes. The sensor unit with microfluidic system was designed to detect the concentration change of cellular acidic metabolites in the extracellular microenvironment rapidly. Characteristic test experiments and cellular metabolism experiments were carried out to determine the performance of microphysiometer. The result showed that sensitivity of microphysiometer is significantly enhanced to sense the fluctuation of cellular metabolism rapidly and sensitively in real-time detection of living cells under physiological condition. With these improvements, the novel microphysiometer holds promise as a utility platform for studying cellular metabolism and evaluating drug effect.

Evaluation of doxorubicin toxicity on cardiomyocytes using a dual functional extracellular biochip.

Nowadays, cardiotoxicity induced by clinical drugs presents a high prevalence and has aroused great attention onto the effective and reliable drug evaluation before clinical treatment. Doxorubicin (Adriamycin), as a type of anthracycline chemotherapy agent for cancer treatment, was restricted in the clinical use because of its cardiotoxicity. In the present work, a dual functional biochip ExCell integrated with microelectrode arrays and interdigitated electrodes was designed to study the electrophysiological function and physical state of cardiomyocytes under the treatment of doxorubicin. Extracellular field potentials and cell-substrate impedance were measured to respectively express these two functions simultaneously in the same culture. The result detected by ExCell presented a portrait of cardiotoxicity induced by doxorubicin. The amplitude of extracellular field potentials decreased to 93%, 82% and 50% at 50 min treatment of doxorubicin with concentrations of 20 µM, 100 µM and 200 µM, respectively. Successively, beating rate decrease, beat-to-beat variation and Ca(2+) flux manifested severe abnormality. The cell-substrate impedance declined continuously in the depressing process of electrophysiological function and cell death was induced in high concentration treatment. All these result indicate that the biochip ExCell has the potential to be a fast-response and subtle tool for high-throughput drug evaluation assays.