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.

National Institute of Health (NIH)
Research Project (R01)
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Peng, Grace
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Weill Medical College of Cornell University
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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Groenendaal, Willemijn; Ortega, Francis A; Krogh-Madsen, Trine et al. (2014) Voltage and calcium dynamics both underlie cellular alternans in cardiac myocytes. Biophys J 106:2222-32
Thounaojam, Umeshkanta S; Cui, Jianxia; Norman, Sharon E et al. (2014) Slow noise in the period of a biological oscillator underlies gradual trends and abrupt transitions in phasic relationships in hybrid neural networks. PLoS Comput Biol 10:e1003622
Bauer, Jennifer A; Lambert, Katherine M; White, John A (2014) The past, present, and future of real-time control in cellular electrophysiology. IEEE Trans Biomed Eng 61:1448-56
Economo, Michael N; Martínez, Joan José; White, John A (2014) Membrane potential-dependent integration of synaptic inputs in entorhinal stellate neurons. Hippocampus 24:1493-505