Early Predictor Tool of Disease Using Label-Free Liquid Biopsy-Based Platforms for Patient-Centric Healthcare

SIMPLE SUMMARY: We proposed a comprehensive early prediction tool based on liquid biopsy for the label-free phenotypic analysis of cell clusters from clinical samples (n = 31). Our custom algorithm analysis, combined with a microfluidic-based tumor model, was designed to assess and stratify cancer patients in a label-free, cost-effective, and user-friendly way. Multiple quantitative phenotypic parameters (cluster size, thickness, roughness, and thickness per area) were derived from the profiling of the patient-derived cell clusters. Our platform could distinguish healthy donors from pretreatment cancer patients with high sensitivity (91.16 ± 1.56%) and specificity (71.01 ± 9.95%). In addition, the ratio of normalized gray value to cluster size (RGVS) parameter was significantly correlated to treatment duration and cancer stage. In conclusion, our patient-centric, early prediction tool will allow the prognosis of patients in a relatively less invasive manner, which can help clinicians identify diseases or indicate the need for new treatment strategies. ABSTRACT: Cancer cells undergo phenotypic changes or mutations during treatment, making detecting protein-based or gene-based biomarkers challenging. Here, we used algorithmic analysis combined with patient-derived tumor models to derive an early prediction tool using patient-derived cell clusters from liquid biopsy (LIQBP) for cancer prognosis in a label-free manner. The LIQBP platform incorporated a customized microfluidic biochip that mimicked the tumor microenvironment to establish patient clusters, and extracted physical parameters from images of each sample, including size, thickness, roughness, and thickness per area (n = 31). Samples from healthy volunteers (n = 5) and cancer patients (pretreatment; n = 4) could be easily distinguished with high sensitivity (91.16 ± 1.56%) and specificity (71.01 ± 9.95%). Furthermore, we demonstrated that the multiple unique quantitative parameters reflected patient responses. Among these, the ratio of normalized gray value to cluster size (RGVS) was the most significant parameter correlated with cancer stage and treatment duration. Overall, our work presented a novel and less invasive approach for the label-free prediction of disease prognosis to identify patients who require adjustments to their treatment regime. We envisioned that such efforts would promote the management of personalized patient care conveniently and cost effectively.