I will focus on our recent work on 'digital assays.' Digital assays – in which ultra-sensitive molecular measurements are made by performing millions of parallel experiments in picoliter droplets – have generated enormous enthusiasm due to their single molecule resolution. We are developing a hybrid microelectronic/microfluidic chip to ‘unlock’ droplet-based assays for clinical use.

All-trans retinoic acid (ATRA) is an essential therapy in treating acute pro-myelocytic leukemia (APL); however, nearly 20% of APL patients are resistant to ATRA. Currently, there are no biomarkers for ATRA resistance. Using mechano-node-pore sensing (mechano-NPS), an electronic method to mechanically phenotype cells, we have shown that ATRA-resistive APL cells are more stiff than ATRA-responsive cells. I will discuss how mechano-NPS could thus potentially be used to monitor APL resistance.

Our lab is interested in isolating neuronal-enriched extracellular vesicles (nEV) from plasma to determine the state of the neuron in real time. We have characterized nEVs using several techniques and interrogated the cargo from people with Alzheimer’s disease, HIV and COVID with the aim of determining plasma biomarkers for neurocognitive decline.

Tumor-derived extracellular vesicles (EVs) have gained much interest as circulating biomarkers for cancer diagnosis and treatment monitoring. We have developed various nanoplasmonic sensing (nPLEX) technologies for the sensitive and robust detection of tumor-derived EVs directly from clinical samples. In this presentation, I will discuss the nPLEX sensing technologies and their applications for cancer diagnosis, and their future directions for clinical translation.

TellBio is an oncology company revolutionizing the detection and treatment of cancer through its unique and proprietary circulating tumor cells (CTCs) technology, TellDx, and complementary therapeutic platform, TellRx. The TellDx CTC system is a diagnostic solution to detect and isolate live CTCs from liquid biopsies. This microfluidic system has agile features to isolate a spectrum of CTC ranging from epithelial, hybrid, and mesenchymal cells. Furthermore, TellDx allows for subsequent multi-omic analyses and ability to capture viable CTCs to develop ex-vivo or xenograft culture models to elucidate mechanisms of biological resistance and drug signaling pathways.

We will highlight our advanced liquid biopsy capabilities, including our new actionable minimal residual disease (MRD) solution, PredicineBEACON, which may provide earlier recurrence detection including detections of actionable variants and emerging resistance mutations.  Additionally, our harmonized NGS assays are accessible in US, China, and ROW to allow truly global clinical trial access and companion diagnostics (CDx) programs.  

Cancer is often detected too late. MCED liquid biopsy tests are designed to harness the power of a variety of biomarkers from various tumors to help detect cancer prior to symptom onset. We’ll share the current evidence for novel multi-analyte approaches to MCED testing that, in combination with standard of care screening, may have the potential to detect more cancers at earlier stages when they are more treatable.

Our second-generation mDETECT liquid biopsy for Triple Negative Breast Cancer is based on the detection of DNA methylation using a targeted next-generation sequencing approach. In an independent validation, cohort is achieved and AUC of 0.97 with a sensitivity of 93% for a specificity of 100%, using 2 mls of serum. It has the potential to quantitatively monitor tumour burden in this aggressive subtype of breast cancer.

The success of precision and immuno-oncology rests on approved genomic biomarkers such as mutations, copy number alterations, tumor mutation burden, and microsatellite instability. While their assessment in ctDNA has been developed, their measurement can be limited by low ctDNA tumor fraction. CTC single-cell NGS is rather unexplored for complementing tissue and ctDNA biomarker detection. We show feasibility and validity of this approach which suggests further exploration of its clinical utility.

A multi-cancer early detection (MCED) test used to complement existing screening could increase the number of cancers detected through population screening, potentially improving clinical outcomes.

I will discuss analytical validation challenges and opportunities in clinical circulating tumor DNA testing. Analyses from the AMP liquid biopsy working group have identified opportunities for validation standardization, which will facilitate additional clinical implementation.

Liquid biopsies are emerging as a complementary approach to traditional tissue biopsies to detect dynamic changes in specific cell populations. Cell-free DNA fragments released into the circulation from dying cells can be traced back to the tissues and cell types they originated from using DNA methylation, an epigenetic regulatory mechanism that is highly cell-type specific. Decoding changes in the cellular origins of cfDNA over time can reveal altered host tissue homeostasis due to local cancer invasion and metastatic spread to distant organs as well as treatment responses.

Liquid biopsies from circulated tumor DNA provide advantages for cancer diagnostics and disease monitoring but can prove challenging to implement. Samples require precise handling and processing to maximize DNA quality, and yield. I will discuss our complete solution for cell-free DNA isolation, including sample sourcing, processing, storage, and downstream genomic analysis.

The development of blood-based, tumor specific biomarkers called real-time liquid biopsy such as circulating tumor cells (CTCs) have made significant advances over the last years in cancer research. In my lecture, I will present the hallmarks of the first and still only nine permanent colon CTC lines from peripheral blood samples of a patient with metastatic colon cancer collected at different time points during treatment and cancer progression.

A feature of tumor cells is their active release of exosomes into the extracellular environment. Harnessing circulating tumor exosome molecular profiles provides a means for a liquid biopsy approach for tumor molecular profiling including a detailed representation of the tumor cell surfaceome to guide therapy.