3D Printed Microfluidics for Cancer Cell Isolation and Sepsis Detection
Microfluidic cell separation techniques have gained significant attention in the field of clinical analysis due to their ability to perform high-throughput separations on small sample sizes. The use of microfluidic separation in clinical analysis offers several advantages, including the ability to perform high-throughput separations with small sample sizes, high sensitivity and specificity, and low cost. These benefits make microfluidic separation a promising tool for the advancement of clinical analysis and disease diagnosis. In this dissertation, Chapter I discusses the detailed fundamentals introduction of microfluidics. Chapter II and Chapter III present the studies of biomarkers used for cancer cells isolation and the application combined with affinity 3D printed microfluidic devices. Chapter IV discusses the study of biomarkers used in the early detection of sepsis and the application combined with 3D printed multi-zone microfluidic device in a clinical study. In Chapter V, the conclusion and prospects for the future are discussed. Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. Cancer cells typically grow quickly, are immature, and are unable to carry out the duties of healthy cells. The mortality of cancer patients will decrease if the cancer prognosis can be identified early (before a disease starts to metastasis). The selection of a biomarker for early cancer detection is crucial. In Chapter II and Chapter III, CD71 and EpCAM are used as cancer biomarkers with our 3D printed microfluidic device to isolate cancer cells. Capture purity and enrichment factor are being studied, in Chapter II, clinical cancer cells were spiked into blood and isolated with breast cancer samples having a purity of 93 ± 6% to 94 ± 10% and an enrichment factor of 1860 ± 120 to 1890 ± 190 and acute lymphoblastic leukemia samples having a purity of 90 ± 10% to 96 ± 7% with an enrichment factor of 1793 ± 200 to 1920 ± 140. The severe and sometimes fatal condition known as sepsis is brought on by an unchecked immunological reaction to infection. Sepsis must be identified and treated as soon as possible to lower the risk of serious consequences and enhance patient outcomes. In Chapter IV, we present a 3D multi-zone microfluidic device provided high sepsis capture purity and high enrichment factor. Anti-CD25, anti-CD64, and anti-CD69 were used as affinity cell capture biomarkers. The performance of our 3D printed multi-zone microfluidic device was assessed in this study, which included 35 septic patients and 10 healthy volunteers. With an AUC of 0.992, we discovered that our combination of anti-CD25, anti-CD64, and anti-CD69 antibodies worked well together to detect sepsis. According to the clinical validation, our multi-parameter microchip provides a potent sepsis assay for clinical point-of-care (POC) applications.
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