Predictable Duty Cycle Modulation through Coupled Pairing of Syringes with Microfluidic Oscillators

The ability to elicit distinct duty cycles from the same self-regulating microfluidic oscillator device would greatly enhance the versatility of this micro-machine as a tool, capable of recapitulating in vitro the diverse oscillatory processes that occur within natural systems. We report a novel approach to realize this using the coordinated modulation of input volumetric flow rate ratio and fluidic capacitance ratio. The demonstration uses a straightforward experimental system where fluid inflow to the oscillator is provided by two syringes (of symmetric or asymmetric cross-sectional area) mounted upon a single syringe pump applying pressure across both syringes at a constant linear velocity. This produces distinct volumetric outflow rates from each syringe that are proportional to the ratio between their cross-sectional areas. The difference in syringe cross-sectional area also leads to differences in fluidic capacitance; this underappreciated capacitive difference allows us to present a simplified expression to determine the microfluidic oscillators duty cycle as a function of cross-sectional area. Examination of multiple total volumetric inflows under asymmetric inflow rates yielded predictable and robust duty cycles ranging from 50% to 90%. A method for estimating the outflow duration for each inflow under applied flow rate ratios is provided to better facilitate the utilization of this system in experimental protocols requiring specific stimulation and rest intervals.

[1]  Shuichi Takayama,et al.  Timing is everything: using fluidics to understand the role of temporal dynamics in cellular systems , 2009 .

[2]  Shuichi Takayama,et al.  Constant flow-driven microfluidic oscillator for different duty cycles. , 2012, Analytical chemistry.

[3]  G. A. Rooke,et al.  Syringe pumps for infusion of vasoactive drugs: mechanical idiosyncrasies and recommended operating procedures. , 1994, Anesthesia and analgesia.

[4]  David J Beebe,et al.  A passive pumping method for microfluidic devices. , 2002, Lab on a chip.

[5]  G. Palade,et al.  INTRACELLULAR TRANSPORT OF SECRETORY PROTEINS IN THE PANCREATIC EXOCRINE CELL , 1968, The Journal of cell biology.

[6]  Keli Xu,et al.  Calcium oscillations increase the efficiency and specificity of gene expression , 1998, Nature.

[7]  D. Beebe,et al.  The present and future role of microfluidics in biomedical research , 2014, Nature.

[8]  James P Landers,et al.  Flow switching in microfluidic networks using passive features and frequency tuning. , 2013, Lab on a chip.

[9]  Mark A Burns,et al.  Microfluidic pneumatic logic circuits and digital pneumatic microprocessors for integrated microfluidic systems. , 2009, Lab on a chip.

[10]  Daniel C Leslie,et al.  Frequency-specific flow control in microfluidic circuits with passive elastomeric features , 2009 .

[11]  Ho Cheung Shum,et al.  Syringe-pump-induced fluctuation in all-aqueous microfluidic system implications for flow rate accuracy. , 2014, Lab on a chip.

[12]  Shuichi Takayama,et al.  Phase-Locked Signals Elucidate Circuit Architecture of an Oscillatory Pathway , 2010, PLoS Comput. Biol..

[13]  Shuichi Takayama,et al.  Analyzing threshold pressure limitations in microfluidic transistors for self-regulated microfluidic circuits. , 2012, Applied physics letters.

[14]  M Weiss,et al.  Syringe size and flow rate affect drug delivery from syringe pumps , 2000, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[15]  H. Gratzner,et al.  Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. , 1982, Science.

[16]  Philip N Duncan,et al.  Pneumatic oscillator circuits for timing and control of integrated microfluidics , 2013, Proceedings of the National Academy of Sciences.

[17]  B. Mosadegh,et al.  Integrated Elastomeric Components for Autonomous Regulation of Sequential and Oscillatory Flow Switching in Microfluidic Devices , 2010, Nature physics.

[18]  Andre Levchenko,et al.  High Content Cell Screening in a Microfluidic Device*S , 2009, Molecular & Cellular Proteomics.

[19]  I. Shmulevich,et al.  Dynamic analysis of MAPK signaling using a high-throughput microfluidic single-cell imaging platform , 2009, Proceedings of the National Academy of Sciences.

[20]  Piotr Garstecki,et al.  Effects of unsteadiness of the rates of flow on the dynamics of formation of droplets in microfluidic systems. , 2011, Lab on a chip.

[21]  Timothy K Lee,et al.  Single-cell NF-κB dynamics reveal digital activation and analogue information processing , 2010, Nature.

[22]  Shuichi Takayama,et al.  Microfluidic oscillators with widely tunable periods. , 2013, Lab on a chip.

[23]  Shuichi Takayama,et al.  Microfluidic automation using elastomeric valves and droplets: reducing reliance on external controllers. , 2012, Small.

[24]  Shuichi Takayama,et al.  Next-generation integrated microfluidic circuits. , 2011, Lab on a chip.

[25]  David J Beebe,et al.  Microfluidic logic gates and timers. , 2007, Lab on a chip.