Measurement of the Drug Sensitivity of Single Prostate Cancer Cells

Abstract

The treatment of cancer faces a serious challenge as cancer cells within patients are heterogeneous and frequently resistant to therapeutic drugs. Here, we introduce a technology enabling the assessment of single cancer cells exposed to different drugs. PCa cells were individually sorted in self-seeding microwells, cultured for 24 h, and then exposed to several drugs to induce (R1881) or inhibit (Enzalutamide/Abiraterone) the secretion of a protein (PSA). Cell viability and PSA secretion of each individual prostate cell were monitored over a 3-day period. The PSA protein secreted by each cell was captured on a PVDF membrane through a pore in the bottom of each well. The basal PSA secretion was found to be 6.1 ± 4.5 and 3.7 ± 1.9 pg/cell/day for LNCaP and VCaP, respectively. After exposure to R1881, the PSA secretion increased by ~90% on average and was not altered for ~10% of the cells. PSA production decreased in the majority of cells after exposure to enzalutamide and abiraterone.

Microfluidic Biochips for Single‐Cell Isolation and Single‐Cell Analysis of Multiomics and Exosomes

“…Reproduced with permission. [ 128 ] Copyright 2021, Mdpi. C) Detection of functionalized antibody magnetic beads based on droplet chips.…”

“…Importantly, because this method immobilizes the antibody on the detection membrane, changing the membrane does not affect the cells in the well and dynamic analysis of secreted proteins can be easily performed (Figure 8B ). [ 128 ] However, the small space of the microwells affects the normal proliferative activity of cells during the detection process, and the single‐detection throughput is also affected by spectral overlap. Some studies have used quenchable magnetic bead encoding, and the detection flux can reach 6 or even higher to overcome spectral overlap, [ 129 ] whereas others have used mass spectrometry (MS) instead of fluorescence, which greatly improves the detection throughput, reaching thousands.…”

“…B) Protein dynamic detection based on a microwell chip, where the antibody membrane for protein detection can be replaced. Reproduced with permission [128]. Copyright 2021, Mdpi.…”

Liquid Biopsy Based Circulating Biomarkers in Metastatic Prostate Cancer

“…Abali et al., quantified protein secretions from LnCAP and VyCAP cell lines in picograms of PSA produced per cell per day. The effect of different drugs on each cell and their PSA secretions (over a period of 24-72 hours) could be quantified ( 93 ). At any time point, the individual cells can be isolated and probed for their molecular composition ( 94 ).…”