Measurement of microchannel fluidic resistance with a standard voltage meter.

A simplified method for measuring the fluidic resistance (R(fluidic)) of microfluidic channels is presented, in which the electrical resistance (R(elec)) of a channel filled with a conductivity standard solution can be measured and directly correlated to R(fluidic) using a simple equation. Although a slight correction factor could be applied in this system to improve accuracy, results showed that a standard voltage meter could be used without calibration to determine R(fluidic) to within 12% error. Results accurate to within 2% were obtained when a geometric correction factor was applied using these particular channels. When compared to standard flow rate measurements, such as meniscus tracking in outlet tubing, this approach provided a more straightforward alternative and resulted in lower measurement error. The method was validated using 9 different fluidic resistance values (from ∼40 to 600kPa smm(-3)) and over 30 separately fabricated microfluidic devices. Furthermore, since the method is analogous to resistance measurements with a voltage meter in electrical circuits, dynamic R(fluidic) measurements were possible in more complex microfluidic designs. Microchannel R(elec) was shown to dynamically mimic pressure waveforms applied to a membrane in a variable microfluidic resistor. The variable resistor was then used to dynamically control aqueous-in-oil droplet sizes and spacing, providing a unique and convenient control system for droplet-generating devices. This conductivity-based method for fluidic resistance measurement is thus a useful tool for static or real-time characterization of microfluidic systems.

Self-regulated, droplet-based sample chopper for microfluidic absorbance detection.

Akin to optical beam chopping, we demonstrate that formation and routing of aqueous droplets in oil can chop a fluidic sample to permit phase sensitive detection. This hand-operated microfluidic sample chopper (µChopper) greatly reduces the detection limit of molecular absorbance in a 27 µm optical path. With direct dependence on path length, absorbance is fundamentally incompatible with microfluidics. While other microfluidic absorbance approaches use complex additions to fabrication, such as fiber coupling and increased optical paths, this self-regulated µChopper uses opposing droplet generators to passively alternate sample and reference droplets at ~10 Hz each. Each droplet's identity is automatically locked-in to its generator, allowing downstream lock-in analysis to nearly eliminate large signal drift or 1/f noise. With a lock-in time constant of 1.9 s and total interrogated volume of 59 nL (122 droplets), a detection limit of 3.0 × 10(-4) absorbance units or 500 nM bromophenol blue (BPB) (29 fmol) was achieved using only an optical microscope and a standard, single-depth (27 µm) microfluidic device. The system was further applied to nanoliter pH sensing and validated with a spectrophotometer. The µChopper represents a fluidic analog to an optical beam chopper, and the self-regulated sample/reference droplet alternation promotes ease of use.

Passively operated microfluidic device for stimulation and secretion sampling of single pancreatic islets.

A passively operated polydimethylsiloxane (PDMS) microfluidic device was designed for sampling of hormone secretions from eight individual murine pancreatic islets in parallel. Flow control was achieved using a single hand-held syringe and by exploiting inherent fluidic resistances of the microchannels (R(sampling) = 700 ± 20 kPa s mm(-3) at 37 °C). Basal (3 mM) or stimulatory (11 mM) glucose levels were applied to islets, with stimulation timing (t(stim)) minimized to 15 ± 2 s using modified reservoirs. Using enzyme-linked immunosorbent assays (ELISA) for postsampling analyses, we measured statistically equal levels of 1 h insulin secretion (1.26 ± 0.26 and 6.55 ± 1.00 pg islet(-1) min(-1), basal and stimulated; 62 islets) compared to standard, bulk sampling methods (1.01 ± 0.224 and 6.04 ± 1.53 pg islet(-1) min(-1), basal and stimulated; 200 islets). Importantly, the microfluidic platform revealed novel information on single-islet variability. Islet volume measurements with confocal reflectance microscopy revealed that insulin secretion had only limited correlation to islet volume, suggesting a more significant role for cellular architecture and paracrine signaling within the tissue. Compared to other methods using syringe pumps or electroosmotic flow control, this approach provides significant advantages in ease-of-use and device disposability, easing the burden on nonexperts.