Label-free counting of affinity-enriched circulating tumor cells (CTCs) using a thermoplastic micro-Coulter counter (μCC)

Coulter counters are used for counting particles and biological cells. Most Coulter counters are designed to analyze a sample without the ability to pre-process the sample prior to counting. For the analysis of rare cells, such as circulating tumor cells (CTCs), it is not uncommon to require enrichment before counting due to the modest throughput of mu CCs and the high abundance of interfering cells, such as blood cells. We report a microfluidic-based Coulter Counter (mu CC) fabricated using simple, low-cost techniques for counting rare cells that can be interfaced to sample pre- and/or post-processing units. In the current work, a microfluidic device for the affinity-based enrichment of CTCs from whole blood into a relatively small volume of similar to 10 mu L was interfaced to the mu CC to allow for exhaustive counting of single CTCs following release of the CTCs from the enrichment chip. When integrated to the CTC affinity enrichment chip, the mu CC could count the CTCs without loss and the cells could be collected for downstream molecular profiling or culturing if required. The mu CC sensor counting efficiency was >93% and inter-chip variability was similar to 1%.