A comparison of microfluidic methods for high-throughput cell deformability measurements

Abstract

The mechanical phenotype of a cell is an inherent biophysical marker of its state and function, with many applications in basic and applied biological research. Microfluidics-based methods have enabled single-cell mechanophenotyping at throughputs comparable to those of flow cytometry. Here, we present a standardized cross-laboratory study comparing three microfluidics-based approaches for measuring cell mechanical phenotype: constriction-based deformability cytometry (cDC), shear flow deformability cytometry (sDC) and extensional flow deformability cytometry (xDC). All three methods detect cell deformability changes induced by exposure to altered osmolarity. However, a dose-dependent deformability increase upon latrunculin B-induced actin disassembly was detected only with cDC and sDC, which suggests that when exposing cells to the higher strain rate imposed by xDC, cellular components other than the actin cytoskeleton dominate the response. The direct comparison presented here furthers our understanding of the applicability of the different deformability cytometry methods and provides context for the interpretation of deformability measurements performed using different platforms.

For the full article: Nature Article

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These tools are being used by Cytovale in identifying patients at risk from COVID-19 complications

BARDA and Cytovale, Inc. are expanding their partnership for additional advanced research and development of a diagnostic system being designed to diagnose sepsis in less than 10 minutes.

Cytovale’s rapid diagnostic system is a deformability cytometry platform, meaning that it analyzes the biomechanical properties of immune cells; this method may enable early and rapid diagnosis of sepsis. Receiving results in less than 10 minutes would enable timely and accurate triage in the emergency department, allow for more effective identification and treatment of sepsis, and help optimize use of valuable hospital resources.

To validate this rapid diagnostic system in identifying patients at risk of viral sepsis, Cytovale’s pilot study specifically will enroll patients suspected of respiratory infections, including COVID-19 patients, prior to conducting full validation studies. This pilot study is an important step in evaluating the system’s performance to rapidly identify the likelihood of sepsis in these patients in the emergency department.

The pilot study represents the expansion of a larger contract, first launched in September 2019, which includes executing analytical and clinical validation studies and preparing for manufacturing scale-up and validation, all of which are necessary for the U.S. Food and Drug Administration to consider clearance of the diagnostic system.

This specific study is part of BARDA’s Rapidly Deployable Capabilities program to identify and pilot near-term innovative solutions for COVID-19, leveraging the development of Cytovale’s rapid diagnostic system under BARDA’s Division of Research Innovation and Venture (DRIVe) Solving Sepsis Program.

This award is one component of BARDA’s rapidly expanding COVID-19 medical countermeasure portfolio; visit BARDA’s COVID-19 Portfolio to learn more.

About the Company:
The following information is provided by the company and does not indicate endorsement by the federal government of the company or its products.

Cytovale, based in San Francisco, Calif., is a medical technology company dedicated to revolutionizing diagnostics using cell mechanics and machine learning, and applying this first to sepsis, a condition whose early detection dramatically improves patient outcomes. For more information visit: cytovale.com.

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