Point of care testing’s immediate results can be transformational in how we treat and diagnose conditions. However, historical challenges in implementation as well as performance have kept POCT from reaching its full impact. But with recent advancements in testing technology as well as shifting demand and expectations around testing, in part due to COVID-19, that’s changing. In this talk Dr. Brian DuChateau will review the advancements in testing technology, how this addresses past pain points, and what this symbolizes for the future of healthcare.

Liquid biopsies in oncology, which analyze tumor-derived material circulating in blood and other bodily fluids, offer considerable clinical potential, including cancer diagnosis, early detection, monitoring treatment response and disease recurrence. Liquid biopsy biomarkers include extracellular vesicles (EVs) are showing great promise. Small EVs (<150 nm) of endocytic origin (exosomes) are produced and released by cells under normal physiology and diseased states. sEVs carry cargo representative of their originating cell including nucleic acids, and a wide assortment of biologically active lipids and proteins. Since sEVs/exosomes travel systemically, efforts are underway to exploit them as biomarkers to detect and monitor disease states.

This presentation will describe new flow-based technologies we developed, from the analysis of single rare cells to individual extracellular vesicles. I will outline the workings of these new tools, describe their performance, and discuss the clinical questions we are addressing with these next-generation flow-based technologies.

Circulating nucleic acid biomarkers from liquid biopsy samples can be valuable tools for disease diagnosis and for interpreting therapeutic response. Digital PCR provides an absolute quantitation of the target being amplified and is known to have increased sensitivity and higher precision over qPCR. The 6-color multiplexing capabilities provided by Crystal Digital PCR™ can be advantageous in identifying and quantifying low levels of circulating cell-free nucleic acid from precious liquid biopsy samples.

Liquid biopsy approaches are playing an instrumental role in biomarker-driven clinical trials.  Predicine provides innovative liquid biopsy solutions including blood- and urine-based genomic profiling, cfDNA and cfRNA analysis, actionable MRD monitoring, low sample input, harmonized liquid biopsy and tissue NGS assay, and CDx development in US and China.

Our research team at UCLA has built a series of nanotechnology-enabled in vitro diagnostics that are capable of processing liquid biopsy samples, i.e., circulating tumor cells (CTCs) and extracellular vesicles (EVs). These nanomaterials-embedded diagnostic platforms, including NanoVelcro CTC Chips, NanoVilli EV Chips, and Click Chips, introduce powerful noninvasive diagnostic solutions for detection, isolation, and characterization of CTCs and EVs in peripheral blood. In my presentation, I will give a progress report on the latest development of our nanotechnology-enabled liquid biopsy platforms, as well as their clinical applications, e.g., prognostic prediction, disease detection/staging, mutational analysis, and transcriptomic profiling. 

As part of the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, the Oncopanel Sequencing Working Group has conducted a cross-laboratory assessment of five leading ctDNA NGS assays. The group first builds a comprehensive set of known positives and negative positions for the contrived reference samples. Sensitivity, reproducibility, and precision are thoroughly examined at different DNA input amounts and variant allele fractions, leading to best practice recommendations for ctDNA liquid biopsy.

Circulating tumor cell (CTC) clusters are highly efficient metastatic precursors in breast cancer. Our recent findings highlight specific DNA methylation dynamics associated with CTC clustering, as well as the involvement of neutrophils in supporting their metastatic ability. Through a drug screen, we highlight the activity of cluster-dissociating agents with immediate clinical applicability. In this presentation, I will summarize our research findings as well as new directions for CTC cluster research and future clinical opportunities.

Lung cancer is the most frequent cause of cancer death many of which attribute to metastasis via CTC. Among surgical cases of lung cancer, preoperative clustered CTC detection is a predictor of recurrence. On the other hand, among patients with no CTC detection before surgery CTC detection only after surgery can occur, which is a predictor of metastasis as well as preoperative clustered CTC. Monitoring CTC pre- and post-surgery reveals positive implication of predictive cancer metastasis, and the CTC around surgery might become a treatment target.

Accumulating evidence in human patients and animal models supports the hypothesis that clusters of tumor cells can complete the entire metastatic journey in a process referred to as collective metastasis. Here I highlight how formation of nanolumina- intercellular compartments between tumor cells- promotes proliferation and metastatic colonization of clusters. I will discuss how the unique properties of tumor cell clusters may offer potential insights into treatment and prevention of metastasis.

Liquid biopsy offers the ability to assess cancer patient's tumor without a costly and invasive tissue biopsy. Epic Science' Comprehensive Cancer Profiling combines CTC analysis, single-cell genomics, and ctDNA sequencing to empower cellular and genomic characterization of the tumor. Join us to learn how academic and pharmaceutical researchers apply Epic's capabilities to clinical and translational research and how Epic's approach promises to revolutionize the development of future diagnostics.

CTC-based liquid biopsies have emerged as a promising tool for cancer diagnostics, treatment selection, and response monitoring. However, low numbers of CTCs in peripheral blood significantly limit their clinical utility. Leukapheresis products obtained by screening whole human blood (~5 liters) can dramatically enhance the number of isolated CTCs to thousands of cells, but the current techniques can only process about 3 to 5% of the sample. In this study, we present a microfluidic scheme that can process a full leukapheresis volume of ~65 mL and recover viable CTCs in a tumor-agnostic manner.

Circulating microRNAs are promising biomarkers for early detection, precision medicine, and companion diagnostics. In this talk, we will share MiRXES' experience in developing and validating a microRNA-based diagnostic for stomach cancer early detection and how this experience became the basis for an industry standard that sets out the key considerations for the design, development, and performance evaluation of microRNA-based clinical diagnostic assays.

Circulating tumor cells (CTCs) that are shed from the primary tumor along with extracellular vesicles (EV) are emerging as a potential avenues for liquid biopsy. The molecular and genetic profiling of CTCs and EVs is a viable alternative to painful, costly, and invasive biopsies. Owing to the recent advances in microfluidics, CTC and EV isolation is becoming increasingly efficient, sensitive and feasible. Although CTCs are more established, EVs are emerging as important biomarkers with high clinical relevance. Emerging microfluidic technologies are promising for not isolating CTCs but also for isolating tumor derived EVs. We present novel integrated microfluidic technologies that enable both functional and genomic assays beyond isolation and quantification. We demonstrate liquid biopsy using CTCs and EVs as a resource to identify genomic alterations in cancer and present the opportunities for diagnosis, therapy and surveillance.

Circulating tumor cells (CTCs) show extreme heterogeneity, therefore analyzing the phenotypic and molecular properties of CTCs at the single cell level will provide valuable information. However, most of the current technologies are not ideal in analyzing live CTCs at single cell level. We have optimized approaches to improve the isolation, analysis, and ex vivo expansion of live single CTCs.