Microscale acoustic disruption of mammalian cells for intracellular product release

• Measurement of detergent-sensitive intracellular products at microscale has been difficult.
• We developed a 96-well plate mechanical disruption method for mammalian cells.
• The method was used to release Varicella-Zoster virus from infected MRC-5 cells.
• This cell disruption method will expand high-throughput cell culture screening.

High-throughput microscale models for cell culture are critical for biopharmaceutical process development and drug discovery compound screening. While analytical methods are readily available for quantifying cell number and secreted product concentration, the recovery and measurement of intracellular products are significantly affected by the method of cell disruption. For example, the detergents often used in product extraction are incompatible with lipid-enveloped viruses. To provide an alternative to detergent-mediated disruption of mammalian cells, we have developed an effective yet gentle mechanical method compatible with 96-well plates using adaptive focused acoustics technology. This method was adapted for the release of Varicella–Zoster virus from MRC-5 cells and then applied to investigate infectious virus yield as a function of the cell density at infection. This microscale, high-throughput mechanical cell disruption method may be applicable to a variety of mammalian cell culture systems and intracellular products, thus expanding the scope of high-throughput screening.

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