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Single-cell phenotypic profiling of circulating tumor cells (CTCs) in the blood of cancer patients can reveal vital tumor biology information. Even though various approaches have been provided to enrich and detect CTCs, it remains challenging for consecutive CTC sorting, enumeration, and single-cell characterizations. Here, we report an integrated microfluidic device (IMD) for single-cell phenotypic profiling of CTCs that enables automated CTCs sorting from whole blood following continuous single-cell phenotypic analysis while satisfying the requirements of both high purity (92 ± 3%) of cell sorting and high-throughput processing capacity (5 mL whole blood/3 h). Using this new technique we test the phenotypes of individual CTCs collected from xenograft tumor-bearing mice and colorectal (CRC) patients at different tumor stages. We obtained a correlation between CTC characterization and clinical tumor stage and treatment response. The developed IMD offers a high-throughput, convenient, and rapid strategy to study individual CTCs toward minimally invasive cancer therapy prediction and disease monitoring and has the potential to be translated to clinic for liquid biopsy.

Background and Aims: Serrated polyps (SPs) and conventional high-risk adenomas (HRAs) derive from two distinct biological pathways but can also occur synchronously. Adults with synchronous SPs and adenomas have been shown to be a high-risk group and may have a unique risk factor profile that differs from adults with conventional HRAs alone. We used the population-based New Hampshire Colonoscopy Registry (NHCR) to examine the risk profile of individuals with synchronous conventional HRAs and SPs., Methods: Our study population included 20,281 first time screening colonoscopies from asymptomatic NHCR participants 40 years or older between 2004-15. Exams were categorized by findings: (1) normal, (2) HRA only (adenomas ≥ 1 cm, villous, high grade dysplasia, multiple adenomas ( > 2) and adenocarcinoma), (3) clinically significant SP (CSSP) only (any hyperplastic polyp ≥ 1 cm, sessile serrated adenomas/polyps or traditional serrated adenomas), and (4) synchronous HRA + CSSP. Risk factors examined included exposure of interest, smoking (never, past, and current/pack years), as well as age, sex, alcohol, education, and family history of colorectal cancer (CRC). Multivariable unconditional logistic regression tested the relation of risk factors with having synchronous HRA + CSSP versus having a normal exam or HRA alone., Results: Among NHCR participants with 18,354 screening colonoscopies (with complete smoking, sex, bowel preparation data, and adequate preparation) there were 16,495 normal; 1309 HRA alone; 461 CSSP alone, and 89 synchronous HRA + CSSP. Current smoking was associated with an almost threefold increased risk for HRA or CSSP, and an eightfold risk for synchronous HRA + CSSP (aOR = 8.66; 95% CI: 4.73-15.86) compared to normal exams. Adults with synchronous HRA + CSSP were threefold more likely to be current smokers than those with HRA alone (aOR = 3.27; 95% CI:1.74-6.16)., Conclusions: Our data suggest that current smokers may be at a higher risk for synchronous CSSP + HRA even when compared to having HRA alone.