A microfluidic platform for drug screening in a 3D cancer microenvironment

Abstract

Development of resistance to chemotherapy treatments is a major challenge in the battle against cancer. Although a vast repertoire of chemotherapeutics is currently available for treating cancer, a technique for rapidly identifying the right drug based on the chemo-resistivity of the cancer cells is not available and it currently takes weeks to months to evaluate the response of cancer patients to a drug. A sensitive, low-cost diagnostic assay capable of rapidly evaluating the effect of a series of drugs on cancer cells can significantly change the paradigm in cancer treatment management. Integration of microfluidics and electrical sensing modality in a 3D tumour microenvironment may provide a powerful platform to tackle this issue. Here, we report a 3D microfluidic platform that could be potentially used for a real-time deterministic analysis of the success rate of a chemotherapeutic drug in less than 12 h. The platform (66 mm × 50 mm; L×W) is integrated with the microsensors (interdigitated gold electrodes with width and spacing 10 μm) that can measure the change in the electrical response of cancer cells seeded in a 3D extra cellular matrix when a chemotherapeutic drug is flown next to the matrix. B16-F10 mouse melanoma, 4T1 mouse breast cancer, and DU 145 human prostate cancer cells were used as clinical models. The change in impedance magnitude on flowing chemotherapeutics drugs measured at 12 h for drug-susceptible and drug tolerant breast cancer cells compared to control were 50552 ± 144 Ω and 28786 ± 233 Ω, respectively, while that of drug-susceptible melanoma cells were 40197 ± 222 Ω and 4069 ± 79 Ω, respectively. In case of prostate cancer the impedance change between susceptible and resistant cells were 8971 ± 1515 Ω and 3281 ± 429 Ω, respectively, which demonstrated that the microfluidic platform was capable of delineating drug susceptible cells, drug tolerant, and drug resistant cells in less than 12 h.

Enabling cell recovery from 3D cell culture microfluidic devices for tumour microenvironment biomarker profiling

“…More specifically, we have developed a method to retrieve cells from 3D collagen ECM scaffolds confined within microfluidic devices using a quick and straightforward enzymatic degradation process which does not affect cell viability. Although collagenase digestion has been already used for this purpose in the literature 33–35 , very little detail is provided on the procedure. To the authors’ knowledge, this is the first time that a method for this purpose has been fully described and characterised.…”

Progress in melanoma modelling in vitro

“…Abaci and co‐workers using a skin‐on‐a‐chip platform with a unique capability to recirculate the medium demonstrated that the cancer drug, doxorubicin, may have direct toxic effects on keratinocyte proliferation and differentiation . Pandya and co‐workers using a microfluidic platform with multiple chambers and perfusion channels were able to delineate the drug susceptible and tolerant/resistant cancer cells in less than 12 hours . In addition, the implementation of nanotechnology‐based microfluidics has given the possibility to explore cell interactions on a microscale level such as those occurring within a tumor immune‐environment .…”

Multifunctional microfluidic chip for cancer diagnosis and treatment

“…A variety of methods based on microfluidic devices have been developed for flexible use in the single-cell manipulation, such as: optical tweezers [110], droplets [111], magnetic beads [112], and deterministic lateral displacement (DLD) separation method [113]. Identifying tumor cells by electrical sensing modality (such as measuring cell impedance magnitude) [114,115], Raman or fluorescence spectroscopy [116] and polymerase chain reaction (PCR) were developed. For example, a microfluidics 3D gel-island chip was reported to isolate single cell, categorize the cancer cell state and detect single cell drug susceptibility.…”