Abstract
Drug-based treatments are the most widely used interventions for cancer management. Personalized drug response profiling remains inherently challenging with low cell count harvested from tumour sample. We present a 96well-formatted microfluidic plate with built-in micro-gap that preserves up to 99.2% of cells during multiple assay/wash operation and only 9,000 cells needed for a single reagent test (i.e. 1,000 cells per test spot x 3 selected concentration x triplication), enabling drug screening and compatibility with conventional automated workstations. Results with MCF7 and MDA-MB-231 cell lines showed that no statistical significance was found in dose-response between the device and conventional 96-well plate control. Primary tumour samples from breast cancer patients tested in the device also showed good IC50 prediction. With drug screening of primary cancer cells must consider a wide range of scenarios, e.g. suspended/attached cell types and rare/abundant cell availability, the device enables high throughput screening even for suspended cells with low cell count since the signature microfluidic cell-trapping feature ensures cell preservation in a multiple solution exchange protocol.
Highlights
Drug-based treatments are the most widely used interventions for cancer management
We designed a micro-gap plate (MGP), shown in Fig. 1, to conduct individual anticancer drug response assay with few cells demanded and less external instruments requirement
Conventional polycarbonate was applied as the material of microgap plate (MGP), which had been proven with high optical transparency, ensured the quality of detecting images
Summary
Drug-based treatments are the most widely used interventions for cancer management. Personalized drug response profiling remains inherently challenging with low cell count harvested from tumour sample. Differential staining cytotoxicity (DiSC) assay, allowed multi-concentrations of different drugs testing on fresh tumour specimens[10,11,12] This assay is capable of discriminating drug effects of cancer cells versus normal cells. Many assays were developed and have shown excellent correlation between in vitro resistance and clinical resistance of the patient’s tumour to same regimen In addition to those conventional assays stated above, microfluidic technology had shown feasibility of anticancer drug screening on cell line. High content drug screening allowed parallel multi-concentration or multi-type of anticancer drug treatment[25,26] These microfluidic devices have been proven as an alternative for future anticancer drug assay, some problems still remained unsolved when regarding with the primary tumour samples. Due to these major obstacles, a more rapid and less cell demanding method with high accuracy is still desirable
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