Journal
ACS SENSORS
Volume 2, Issue 6, Pages 773-780Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acssensors.7b00122
Keywords
microfluidic; SERS; pharmacokinetics; dual-drug HeLa; SKBR3; silver nanoparticles
Funding
- State Key Program of National Natural Science of China [61535003]
- Excellent Youth Foundation of Jiangsu Province [BK20140023]
- National Key Basic Research Program of China [2015CB352002]
- National Science Foundation of China [61177033, 61275182]
- Scientific Research Foundation of Graduate School of Southeast University [YBPY1507]
- Nature Science Foundation of Jiangsu Province [BK20140635]
- Science Foundation for the Excellent Youth Scholars of Southeast University
- Fundamental Research Funds for the Central Universities
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Synergistic effects of dual or multiple drugs have attracted great attention in medical fields, especially in cancer therapies. We provide a programmable microfluidic platform for pharmacokinetic detection of multiple drugs in multiple cells. The well-designed microfluidic platform includes two 2 X 3 microarrays of cell chambers, two gradient generators, and several pneumatic valves. Through the combined use of valves and gradient generators, each chamber can be controlled to infuse different kinds of living cells and drugs with specific concentrations as needed. In our experiments, 6-mercaptopurine (6MP) and methimazole (MMI) were chosen as two drug models and their pharmacokinetic parameters in different living cells were monitored through intracellular SERS spectra, which reflected the molecular structure of these drugs. The dynamic change of SERS fingerprints from 6MP and MMI molecules were recorded during drug metabolism in living cells. The results indicated that both 6MP and MMI molecules were diffused into the cells within 4 min and excreted out after 36 h. Moreover, the intracellular distribution of these drugs was monitored through SERS mapping. Thus, our microfluidic platform simultaneously accomplishes the functions to monitor pharmacokinetic action, distribution, and fingerprint of multiple drugs in multiple cells. Owing to its real-time, rapid speed, high-precision, and programmable capability of multiple-drug and multicell analysis, such a microfluidic platform has great potential in drug design and development.
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