The ability of experimentalists to perturb biological systems has traditionally been limited to rigid pre- programmed (open loop) protocols. In contrast, real-time control allows the researcher to dynamically probe a biological system with parameter perturbations that are calculated functions of instantaneous system measurements (closed loop), thereby providing the ability to address diverse unanswered questions that are not amenable to traditional approaches. While real-time control applications are abundant throughout biological research, including, e.g., dynamic probing of ion-channel function in neurons and cardiac cells, adoption of such approaches lags. Unfortunately, for a number of technical reasons, real-time control is not possible with standard computer operating systems and software. Furthermore, commercial real-time systems are costly and often tailored for industrial applications. To circumvent these limitations, we developed a fast and highly versatile real- time biological experimentation system known as the Real-Time eXperiment Interface (RTXI). Based on Real-Time Linux, RTXI is open source and free, can be used with an extensive range of experimentation hardware, and can be run on Linux or Windows computers (when temporarily booted into Linux using an RTXI LiveCD). Importantly, RTXI has been adopted by many prominent scientific groups and has become an invaluable part of their scientific programs. In addition to the need to update and maintain RTXI for those, and future, end users, there remain important development avenues that would significantly expand its functionality and broaden its utility for the biological research community. Thus, for this competitive renewal, we propose: 1. To keep RTXI on the cutting edge by periodically updating its base code and core modules. 2. To enable new experiment paradigms. 3. To use RTXI's module architecture as the foundation for new protocol classes and application suites. 4. To improve the level of user support and documentation. The work proposed here would help ensure that RTXI not only remains a valuable research tool for a varied group of biological scientists, but that its utility, and the experiments it enables, continue to expand.

Public Health Relevance

Traditional experimentation protocols are not always capable of fully probing the mechanisms of complex biological systems. We have developed a free, open-source software system known as Real-Time eXperiment Interface (RTXI) that enables experimentalists to perform innovative protocols that are adapted on the fly to optimize information acquisition and experiment control during the course of an experiment. This project, which aims to expand the functionality of RTXI in significant ways, will further the abilities of biological scientists to use such protocols to learn important information about biological systems ranging from the heart to the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB016407-11
Application #
8884411
Study Section
Special Emphasis Panel (NOIT)
Program Officer
Peng, Grace
Project Start
2013-08-01
Project End
2017-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
11
Fiscal Year
2015
Total Cost
$647,330
Indirect Cost
$176,221
Name
Weill Medical College of Cornell University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Patel, Yogi A; Kim, Brian S; Butera, Robert J (2018) Kilohertz Electrical Stimulation Nerve Conduction Block: Effects of Electrode Material. IEEE Trans Neural Syst Rehabil Eng 26:11-17
Patel, Yogi A; Kim, Brian S; Rountree, William S et al. (2017) Kilohertz Electrical Stimulation Nerve Conduction Block: Effects of Electrode Surface Area. IEEE Trans Neural Syst Rehabil Eng 25:1906-1916
Patel, Yogi A; George, Ansel; Dorval, Alan D et al. (2017) Hard real-time closed-loop electrophysiology with the Real-Time eXperiment Interface (RTXI). PLoS Comput Biol 13:e1005430
Patel, Yogi A; Saxena, Tarun; Bellamkonda, Ravi V et al. (2017) Kilohertz frequency nerve block enhances anti-inflammatory effects of vagus nerve stimulation. Sci Rep 7:39810
Brown, Tashalee R; Krogh-Madsen, Trine; Christini, David J (2016) Illuminating Myocyte-Fibroblast Homotypic and Heterotypic Gap Junction Dynamics Using Dynamic Clamp. Biophys J 111:785-797
Krogh-Madsen, Trine; Sobie, Eric A; Christini, David J (2016) Improving cardiomyocyte model fidelity and utility via dynamic electrophysiology protocols and optimization algorithms. J Physiol 594:2525-36
Norman, Sharon E; Butera, Robert J; Canavier, Carmen C (2016) Stochastic slowly adapting ionic currents may provide a decorrelation mechanism for neural oscillators by causing wander in the intrinsic period. J Neurophysiol 116:1189-98
Brown, Tashalee R; Krogh-Madsen, Trine; Christini, David J (2015) Computational Approaches to Understanding the Role of Fibroblast-Myocyte Interactions in Cardiac Arrhythmogenesis. Biomed Res Int 2015:465714
Tikidji-Hamburyan, Ruben A; Martínez, Joan José; White, John A et al. (2015) Resonant Interneurons Can Increase Robustness of Gamma Oscillations. J Neurosci 35:15682-95
Patel, Yogi A; Butera, Robert J (2015) Differential fiber-specific block of nerve conduction in mammalian peripheral nerves using kilohertz electrical stimulation. J Neurophysiol 113:3923-9

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