“Flow Valve” Microfluidic Devices for Simple, Detectorless, and Label-Free Analyte Quantitation

Abstract

Simplified analysis systems that offer the performance of benchtop instruments but the convenience of portability are highly desirable. We have developed novel, miniature devices that feature visual inspection readout of a target’s concentration from a ~1 μL volume of solution introduced into a microfluidic channel. Microchannels are constructed within an elastomeric material, and channel surfaces are coated with receptors to the target. When a solution is flowed into the channel, the target crosslinks multiple receptors on the surface, resulting in constriction of the first few millimeters of the channel and stopping of flow. Quantitation is performed by measuring the distance traveled by the target solution in the channel before flow stops. A key advantage of our approach is that quantitation is accomplished by simple visual inspection of the channel, without the need for complex detection instrumentation. We have tested these devices using the model system of biotin as a receptor and streptavidin as the target. We have also characterized three factors that influence flow distance: solution viscosity, device thickness, and channel height. We found that solution capillary flow distance scales with the negative logarithm of target concentration and have detected streptavidin concentrations as low as 1 ng/mL. Finally, we have identified and evaluated a plausible mechanism wherein time-dependent channel constriction in the first few millimeters leads to concentration-dependent flow distances. Their simplicity coupled with performance makes these “flow valve” systems especially attractive for a host of analysis applications.

Microfluidic devices for label-free and non-instrumented quantitation of unamplified nucleic acids by flow distance measurement

“…Figure S3A shows an unfilled channel that is clearly visible in the photograph, while Figure S3B shows a microchannel partially filled with buffer solution that can be easily distinguished from the unfilled portion. In our prior work, buffer solution flowed to the end of 13–17 μm tall channels; 1 however, in the current studies, the shorter 11 μm height channels in combination with solution evaporation led to only partial channel filling. In either case the flow distance can readily be determined by visual examination.…”

“…These results agree with our expectation that higher target concentrations cause more rapid channel constriction which leads to shorter flow distances, while lower target concentrations result in slower channel constriction that yields longer flow distances, as we showed previously. 1 …”

“…Lower model target concentrations have greater maximum flow distances and flow times. Thus, flow time, in addition to flow distance, 1 could be used to determine the concentration of target in a solution flowed in our devices.…”

“…Although rounded microchannel cross sections were used as before 1 because of the ease of fabrication, alternate channel geometries such as sigmoidal or trapezoidal could be explored if more complex molds could be made readily. The microchannels in the devices used for flow distance experiments were 11 μm tall and 58 μm wide with a 0.5 mm PDMS top layer thickness.…”

“…We previously developed microfluidic devices wherein visually observed flow distances correlated with a model analyte’s concentration. 1 Here, we significantly expand over this prior result to demonstrate the measurement of unamplified DNA analogues of microRNAs (miRNAs), biomarkers whose levels can be altered in disease states. We have developed a method for covalently attaching nucleic acid receptors on poly(dimethylsiloxane) microchannel surfaces by silane and cross-linker treatments.…”