An integrated microfluidic chip for isolation, culture and drug susceptibility testing of cancer cells

Abstract

“Cancer patients with advanced disease are characterized by intrinsic challenges in predicting drug response patterns, often leading to ineffective treatment. Current clinical practice for treatment decision-making is commonly based on primary or secondary tumour biopsies, yet when disease progression accelerates, tissue biopsies are not performed on a regular basis. It is in this context that liquid biopsies may offer a unique window to uncover key vulnerabilities, providing valuable information about previously underappreciated treatment opportunities. Here, we present MyCTC chip, a novel microfluidic device enabling the isolation, culture and drug susceptibility testing of cancer cells derived from liquid biopsies. Cancer cell capture is achieved through a label-free, antigen-agnostic enrichment method, and it is followed by cultivation in dedicated conditions, allowing on-chip expansion of captured cells. Upon growth, cancer cells are then transferred to drug screen chambers located within the same device, where multiple compounds can be tested simultaneously. We demonstrate MyCTC chip performance by means of spike-in experiments with patient-derived breast circulating tumour cells, enabling >95% capture rates, as well as prospective processing of blood from breast cancer patients and ascites fluid from patients with ovarian, tubal and endometrial cancer, where sensitivity to specific chemotherapeutic agents was identified. Together, we provide evidence that MyCTC chip may be used to identify personalized drug response patterns in patients with advanced metastatic disease and with limited treatment opportunities.

 

“MyCTC chip design. a Design of the MyCTC chip, containing a PDMS layer (top) and COC layer including the microfluidic structures (bottom). b Image showing the MyCTC chip, including a detailed view of the capture and culture section (red) and drug screen chamber (blue). c Focus stacked images showing the capture and culture chamber and drug screen chamber. d Schematic representation of the CTC capture process of the MyCTC chip” Reproduced under a Creative Commons Attribution 4.0 International License from Schwab, F.D., Scheidmann, M.C., Ozimski, L.L. et al. MyCTC chip: microfluidic-based drug screen with patient-derived tumour cells from liquid biopsies. Microsyst Nanoeng 8, 130 (2022).


Figures and the abstract are reproduced from Schwab, F.D., Scheidmann, M.C., Ozimski, L.L. et al. MyCTC chip: microfluidic-based drug screen with patient-derived tumour cells from liquid biopsies. Microsyst Nanoeng 8, 130 (2022). https://doi.org/10.1038/s41378-022-00467-y
 under a Creative Commons Attribution 4.0 International License.


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MyCTC chip: microfluidic-based drug screen with patient-derived tumour cells from liquid biopsies