Microfluidic Tool Box as Technology Platform for Hand-Held Diagnostics

Abstract

Background: Use of microfluidics in point-of-care testing (POCT) will require on-board fluidics, self-contained reagents, and multistep reactions, all at a low cost. Disposable microchips were studied as a potential POCT platform. Methods: Micron-sized structures and capillaries were embedded in disposable plastics with mechanisms for fluidic control, metering, specimen application, separation, and mixing of nanoliter to microliter volumes. Designs allowed dry reagents to be on separate substrates and liquid reagents to be added. Control of surface energy to ؎5 dyne/cm 2 and mechanical tolerances to <1 m were used to control flow propulsion into adsorptive, chromatographic, and capillary zones. Fluidic mechanisms were combined into working examples for urinalysis, blood glucose, and hemoglobin A 1c testing using indicators (substances that react with analyte, such as dyes, enzyme substrates, and diazonium salts), catalytic reactions, and antibodies as recognition components. Optical signal generation characterized fluid flow and allowed detection. Results: We produced chips that included capillary geometries from 10 to 200 m with geometries for stopping and starting the flow of blood, urine, or buffer; vented chambers for metering and splitting 100 nL to 30 L; specimen inlets for bubble-free specimen entry and containment; capillary manifolds for mixing; microstructure interfaces for homogeneous transfer into separation membranes; miniaturized containers for liquid storage and release; and moisture vapor barrier seals for

Microfluidic whole-blood immunoassays

“…The detection limit of HBsAg and Anti-HBs were 0.51 ng/mL and 8.6 mIU/mL, respectively. Similar research was also reported by Pugia et al (2005).…”

Towards non- and minimally instrumented, microfluidics-based diagnostic devices

“…Simple, commercially available, off-the-shelf solutions are available to perform specimen metering prior to introduction of a specimen onto the POC device. Compelling microfluidic solutions to on-device metering include the use of capillaries 19. A major challenge to diagnostic platforms which has not yet been successfully addressed is developing a robust, user-independent interface between the specimen metering device and the diagnostic device.…”

“…Many of these form the basis of diagnostic immunoassays, including lateral flow tests. These approaches have also been applied towards the development of disposable microfluidic devices 19,28. In general, immunoassays can detect protein quantities down to pictogram levels, which is, for example, sufficient for the detection of antibodies to many pathogens; for direct detection of the presence of pathogens, however, NAATs such as PCR-based nucleic acid amplification can provide much better sensitivity (down to the single copu level).…”

“…Also, reports of disposable microfluidic devices with little or no instrumentation for POC diagnostics are appearing 19,24,39–42. One such report utilizes pressurized gas in a micro-reservoir as an energy source to control sequencing on a disposable card 42.…”

Autonomous capillary system for one-step immunoassays

“…(Wild 2005a) Novel platforms for immunoassays are emerging with the advent of miniaturization and microfluidics in which multiple functions, such as metering and preprocessing of a sample, analysis, recording and calibration of the results, can all be done on a portable platform. (Pugia et al 2005;Yager et al 2006) We are interested in applying the concept of autonomous capillary system (CS) to the detection of disease markers for pointof-care testing of patients, with the ultimate goal of detecting a few related disease markers in less than approximately 10 min, with 2 μL of sample or less, and with only one step of handling. Another important goal is to devise a flexible approach where the volume of sample, the number of analytes to be detected, and the flow conditions of the assays can easily be adjusted by only a minor redesign of the CS.…”