title: Microprocessor-based integration of microfluidic control for the implementation of automated sensor monitoring and multithreaded optimization algorithms.
abstract: Microfluidic applications range from combinatorial synthesis to high throughput screening, with platforms integrating analog perfusion components, digitally controlled micro-valves and a range of sensors that demand a variety of communication protocols. Currently, discrete control units are used to regulate and monitor each component, resulting in scattered control interfaces that limit data integration and synchronization. Here, we present a microprocessor-based control unit, utilizing the MS Gadgeteer open framework that integrates all aspects of microfluidics through a high-current electronic circuit that supports and synchronizes digital and analog signals for perfusion components, pressure elements, and arbitrary sensor communication protocols using a plug-and-play interface. The control unit supports an integrated touch screen and TCP/IP interface that provides local and remote control of flow and data acquisition. To establish the ability of our control unit to integrate and synchronize complex microfluidic circuits we developed an equi-pressure combinatorial mixer. We demonstrate the generation of complex perfusion sequences, allowing the automated sampling, washing, and calibrating of an electrochemical lactate sensor continuously monitoring hepatocyte viability following exposure to the pesticide rotenone. Importantly, integration of an optical sensor allowed us to implement automated optimization protocols that require different computational challenges including: prioritized data structures in a genetic algorithm, distributed computational efforts in multiple-hill climbing searches and real-time realization of probabilistic models in simulated annealing. Our system offers a comprehensive solution for establishing optimization protocols and perfusion sequences in complex microfluidic circuits.
authors.affiliation: Grass Center for Bioengineering, The Hebrew University of Jerusalem, Edmond J. Safra Campus, 91904, Jerusalem, Israel.
authors.forename: Elishai
authors.initials: E
authors.lastname: Ezra
authors.forename: Idan
authors.initials: I
authors.lastname: Maor
authors.forename: Danny
authors.initials: D
authors.lastname: Bavli
authors.forename: Itai
authors.initials: I
authors.lastname: Shalom
authors.forename: Gahl
authors.initials: G
authors.lastname: Levy
authors.forename: Sebastian
authors.initials: S
authors.lastname: Prill
authors.forename: Magnus S
authors.initials: MS
authors.lastname: Jaeger
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Nahmias
mesh_terms: D000465:Algorithms; D057205:Automation, Laboratory; D015374:Biosensing Techniques / Q000295:instrumentation; D002138:Calibration; D002460:Cell Line; D055664:Electrochemical Techniques / Q000295:instrumentation; D004581:Electronics; D004867:Equipment Design; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000032:analysis; D008099:Liver / Q000473:pathology; D008838:Microcomputers; D044085:Microfluidics / Q000295:instrumentation*; D019904:Polymethyl Methacrylate / Q000737:chemistry; D011312:Pressure; D012402:Rotenone / Q000737:chemistry
chemical_list: D012402:Rotenone; D019344:Lactic Acid; D019904:Polymethyl Methacrylate