Journal
ANALYTICAL CHEMISTRY
Volume 90, Issue 23, Pages 13969-13977Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.8b03456
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Funding
- National Science Foundation [ECCS-0846502, DBI-1256193]
- National Institutes of Health [R21CA173243, NIEHS-P42ES004699, R01CA115483, R01EB012569]
- Fundamental Research Funds for the Central Universities [lzujbky-2018-135]
- NATIONAL CANCER INSTITUTE [R01CA115483] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB012569] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P42ES004699] Funding Source: NIH RePORTER
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Traditional high-throughput drug combination screening requires automatic pipetting of drugs into high-density microtiter plates. Here, a drug-on-pillar platform is proposed for efficient combination drug screening. Using the proposed approach, combination drug screening can be carried out in a plug-and-play manner, allowing for high-throughput screening of large permutations of drug combinations at various concentrations, such that drug dispensing and cell-based screening can be temporally separated and therefore can potentially be performed at distant laboratories. The dispensing is implemented using our recently developed microfluidic pneumatic printing platform, which features a low-cost disposable cartridge that minimizes cross contamination. Moreover, our previously developed drug nanoformulation method with amphiphilic telodendrimers has been utilized to maintain drug stability in a dry form, allowing for convenient drug storage, shipping, and subsequent rehydration. Combining the features described above, we have implemented a 1260-spot drug combination array to study the effect of paired drugs against MDA-MB-231 triple negative human breast cancer cells. This study supports the feasibility of the drug-on-pillar platform for combination drug screening and has provided valuable insight into drug combination efficacy against breast cancer.
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