SELECTBIO - Extracellular Vesicles & Cell-Free RNAs 2023 Biographies

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Dielectrophoresis Based Collection of Extra Cellular Vesicles and On Chip Analysis of Nucleic Acid Payload

Wednesday, 29 November 2023 at 18:00

Add to Calendar ▼2023-11-29 18:00:002023-11-29 19:00:00Europe/LondonDielectrophoresis Based Collection of Extra Cellular Vesicles and On Chip Analysis of Nucleic Acid PayloadExtracellular Vesicles and Cell-Free RNAs 2023 in Laguna Hills, CaliforniaLaguna Hills, CaliforniaSELECTBIOenquiries@selectbiosciences.com

Differentiating patients with pancreatic cancer (PDAC) from patients with precancerous intraductal papillary mucinous neoplasms (IPMN) and pancreatitis is a challenge using traditional blood-based biomarkers like CA 19-9. Extracellular vesicle (EV) nanoparticles are a valuable source of cancer-derived biomarkers that are released by tumors into circulation throughout their development. These particles include extracellular vesicles, organelle fragments, and cell free DNA (cf-DNA) nanoparticles. However, it is a challenge to use these nanoparticles for clinical diagnostic applications due the difficulty of recovering them from plasma for analysis. We address this challenge through the use of high conductance dielectrophoresis (DEP) to simultaneously recover different nanoparticle types from a single undiluted plasma sample in a quick and easy microfluidic chip format. This method takes advantage of the difference in the dielectric properties between the nanoparticles and the surrounding plasma to create a force that pulls nanoparticles down to an electrode array. The particles are held with enough force to remove the bulk plasma using a fluidic wash. This can simultaneously collect both EVs and cf-DNA nanoparticles around the edges of the electrodes used to generate the DEP force. The combination of EV biomarkers (Glypican-1) and the level of cf-DNA nanoparticles can be used to successfully differentiate PDAC patients from patients with benign pancreatic diseases using a blinded cohort study design. This can also differentiate between PDAC patients and patients with IPMN making this study among the first that we are aware of developing a multiomic threshold that can distinguish between PDAC and IPMN lesions. This is clinically important because IPMNs are a major source of false positives for multiomic biology-based screening. This multiomic biomarker panel had a sensitivity of 0.92, a specificity of 0.88, and an AUC of 0.80 in differentiating between PDAC and benign pancreatic diseases, which is comparable to the traditional invasive endoscopic ultrasound-guided fine needle aspiration (EUS/FNA) diagnostic procedure (AUC 0.79). This new dielectrophoresis-based technique shows multiple types of cancer-derived nanoparticles can be quickly and easily recovered from a single plasma sample and that their associated biomarkers are promising for future use in clinical diagnostics.

Stuart Ibsen, Assistant Professor, The Knight Cancer Institute’s Cancer Early Detection Advanced Research Center (CEDAR), Oregon Health and Science University

My research group’s overall scientific mission is to develop an understanding of the nanoparticles released by tumors into circulation. This includes the role that cancer phenotypes play in the production of these nanoparticles, how the nanoparticles interact with tissues throughout the body, and how these particles can be used clinically for cancer detection and screening. In order to answer these questions, my goal is to develop high conductance dielectrophoresis (DEP) techniques to recover cancer-derived nanoparticles straight from human plasma for the characterization of their cancer related biomarker payloads. In particular, my research has focused on characterizing their biomarker payloads through immunostaining and PCR based methods. My group brings a unique approach to the field of cancer liquid biopsy through the development of these DEP techniques that are capable of collecting multiple different nanoparticle types simultaneously from the same plasma sample. Our team is committed to enable the use of circulating nanoparticles for clinical diagnosis applications.