Analyses or workflows that require reduced reagent consumption, reduced user touch points, and/or workflow automation are enabled through the use of microfluidics. Our team developed a novel method for tissue multiplexing, which required manual handling of the sample for staining, imaging and destaining, however, a manual workflow is not always ideal, particularly in a high-throughput setting. A microfluidic flow cell was developed to replace such manual slide handling, however, its use and applicability can extend to any technology or platform that requires cost-savings (materials, reagents, etc.) and time-savings (labor, automation, etc.) and processes samples through the controlled delivery/application of reagents.
Our approach was to design and develop a microfluidic device that maintained compatibility with standard biological samples and workflows; efficiently automated biological assays with equivalent performance to the benchtop methods; was easily integrated into microscopy platforms while enabling high resolution imaging; was manufacturable. Our end goal was for the microfluidic device to be used as a consumable – one device per biological sample – and for the user to easily mate the device to the sample and their existing wetware and imaging workflows.
Our final device design consisted of a four main materials: silicone over-molded cover-slip; pressure sensitive adhesive (PSA); thin film fluidic connector and mounting substrate. Together, the silicone over-molded cover-slip and PSA created a chamber that encapsulated the sample and the channels that route to/from the chamber. The PSA provided a leak-proof seal under normal operating conditions. This sub-assembly was then applied to a mounting substrate that contained the sample or served as the capture surface for a sample, creating a microfluidic flow cell. The thin film fluidic connector allowed for simple fluidic connections to the larger system that controlled the delivery and flow of reagents through the flow cell and its chamber. The cover-slip lid of the flow cell enabled high quality interfacing with standard analysis platforms (microscopy).
A microfluidic flow cell and corresponding subsystem, known as a carrier, were designed and developed, creating a standalone instrument. The carrier consisted of a miniaturized fluidic cartridge and a miniature fluidic system. It contained peristaltic pumps, an optical and/or bubble sensor for QC, a control board, and reagent reservoirs while simultaneously maintaining the footprint of a standard well plate compatible with microscopy platforms. The subsystem mated with a receiver that provided power and sent software-controlled operations for executing assays. As a result, the standalone subsystem could easily be integrated in a larger system processing one sample at a time or a work cell that processes multiple samples in parallel. Studies using the standalone subsystem demonstrate automated iterative staining, inactivation and imaging of biological samples with equivalent staining intensity and specificity to the standard benchtop process.
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Our Expertise
Capabilities utilized for Microfluidic Flow Cell for Cell Analysis project
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Biosciences
Working from the molecular scale through human health and disease by building novel technology solutions for cell analysis and imaging applications
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MEMS & Microsystems
Integrating and synchronizing complex measurements to operate in our customer's products within highly constrained environments
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