Phase-Optimized Peristaltic Pumping by Integrated Microfluidic Logic

Abstract

Microfluidic droplet generation typically entails an initial stabilization period on the order of minutes, exhibiting higher variation in droplet volume until the system reaches monodisperse production. The material lost during this period can be problematic when preparing droplets from limited samples such as patient biopsies. Active droplet generation strategies such as antiphase peristaltic pumping effectively reduce stabilization time but have required off-chip control hardware that reduces system accessibility. We present a fully integrated device that employs on-chip pneumatic logic to control phase-optimized peristaltic pumping. Droplet generation stabilizes in about a second, with only one or two non-uniform droplets produced initially.

Keywords: droplets; microfluidics; micropump; pneumatic logic; point-of-care.

Figure 1

Design of integrated controller for droplet generator. (a) An inverter gate is created by attaching high and low resistance channels to opposite sides of a valve. Channels on the top and bottom layers are shown in red and blue, respectively. A top-down valve detail shows dimensions of the valves used in this study (length L = 0.5 mm, width W = 1 mm). Cross-section valve detail shows an open valve (upper) and closed valve (lower) with elastomeric membrane in green (thickness T = 250 µm) and depth of the displacement chamber (depth D = 150 µm). (b) The transfer function of a laser-cut inverter gate produces a sharp non-linear switch in output vacuum as input vacuum is increased (solid line, valve opening) and decreased (dashed line, valve closing). (c) Block diagram of the droplet system. A ring oscillator created from inverter gates synchronizes four peristaltic pumps. (d) Photo of the device generating water-in-oil droplets containing blue and red dye (scale bar = 3 mm).

Figure 2

Optimizing droplet monodispersity. Distributions of droplet volumes produced by design iterations (a) Version 23: five-inverter two chamber pump, (b) Version 28: three-inverter single chamber pump with capacitors, (c) Version 32: three-inverter single chamber pump with larger capacitors. All distributions were sampled at steady state with N > 40. (d) The total output flow rate produced by the optimized droplet generator (version 32). The peak flow rate (red dashed lines) delivered by each pump cycle increased from 38.9 µL/min to 52.3 µL/min as operating vacuum increased from 25 kPa to 50 kPa.

Figure 3

Optimizing pump waveform synthesis. (a) Pump operation was monitored with high-speed video. The reflection of incident light from the membrane of each pump valve was used to detect valve state (open or closed). Dashed colored lines show the area of the image analyzed for each valve. Scale bar = 3 mm. (b) Valve detail shows open valves reflect more light back the camera. (c) Time traces of normalized reflected light from each valve from device versions 27 (top) and version 32 (bottom). 1 = valve open (vacuum pressure), 0 = valve closed (atmospheric pressure). Adding large capacitors before and after each row of pump valves (version 32) increased the time required to open each row of valves and the subsequent inverter gate, preventing all pump stages (A, B, and C) from being open simultaneously (shaded rectangle), which resulted in improved pump performance. (d) Illustrations of device versions 27 and 32. Channels in the top and bottom layers are shown in blue and red, respectively.

Figure 4

Electricity-free droplet generation. (a) A 60 mL locking syringe supplies enough vacuum pressure (blue line) to generate droplets (black circles) for over 10 min. The change in volume is minimal for vacuum pressures greater than 50 kPa. For the first 200.6 s (dashed red line), 465 droplets were produced with a CV < 5% and a mean volume of 16.52 nL. (b) Adding a vacuum regulator to the syringe output can provide a stable vacuum pressure for a short time but produced fewer uniform-sized droplets. In the first 67.4 s, 158 droplets with a mean volume of 21.77 nL were produced with a CV < 5% (dashed red line). In both graphs, the first two droplets generated were omitted from volume calculations to account for system stabilization.