A Microfluidic Platform for Precision Small-volume Sample Processing and Its Use to Size Separate Biological Particles with an Acoustic Microdevice

Abstract

A major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15-1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection, system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.

Clinical-Scale Cell-Surface-Marker Independent Acoustic Microfluidic Enrichment of Tumor Cells from Blood

“…Hence, the acoustic micro-fluidic platform is able to process 5 mL (RBC − ) blood diluted 1:2 in close to 2 hours. This instrument was designed so that a non-expert operator can produce repeatable sample treatments similar to Fong et al 35 .…”

“…Cell suspension with concentrations up to 3 × 10 6 cells/mL can be processed without compromising separation accuracy. Hence, the acoustic microfluidic platform is able to process 5 mL of RBC – blood diluted 1:2 in close to 2 h. This instrument was designed so that a nonexpert operator can produce repeatable sample treatments similar to those of Fong et al…”

Current Nucleic Acid Extraction Methods and Their Implications to Point-of-Care Diagnostics

“…Finally yet importantly, there is concern about the volume of sample needed to obtain a meaningful results [ 100 ]. Because the volume of buffers and, therefore, of harsh chemicals used for cell lysis is directly proportional to the volume of the sample, POC-Dx tests are most useful in illness where the pathogen is present in higher counts, such as virus and most bacterial infections.…”

3D-Printed Modular Microfluidic Device Enabling Preconcentrating Bacteria and Purifying Bacterial DNA in Blood for Improving the Sensitivity of Molecular Diagnostics

“…IMS has been often used in microfluidic devices (µFDs) made of polydimethylsiloxane (PDMS). However, these µFDs can handle only a small volume of sample [19] because they consist of thin microchannels. Molds for the µFDs are usually made by photolithography, which is known to be not suitable for fabricating round structures such as spiral and circular channels [20,21].…”