{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:46:10Z","timestamp":1771548370975,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,6,30]],"date-time":"2018-06-30T00:00:00Z","timestamp":1530316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003032","name":"Association Nationale de la Recherche et de la Technologie","doi-asserted-by":"publisher","award":["HYBIOPACS- ANR 2010-EMMA-031-02"],"award-info":[{"award-number":["HYBIOPACS- ANR 2010-EMMA-031-02"]}],"id":[{"id":"10.13039\/501100003032","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003032","name":"Association Nationale de la Recherche et de la Technologie","doi-asserted-by":"publisher","award":["ISLET CHIP - ANR 2013-PRTS-0017"],"award-info":[{"award-number":["ISLET CHIP - ANR 2013-PRTS-0017"]}],"id":[{"id":"10.13039\/501100003032","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003032","name":"Association Nationale de la Recherche et de la Technologie","doi-asserted-by":"publisher","award":["HYRENE - ANR 2010-BLANC-0316-01"],"award-info":[{"award-number":["HYRENE - ANR 2010-BLANC-0316-01"]}],"id":[{"id":"10.13039\/501100003032","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Enhanced understanding and control of electrophysiology mechanisms are increasingly being hailed as key knowledge in the fields of modern biology and medicine. As more and more excitable cell mechanics are being investigated and exploited, the need for flexible electrophysiology setups becomes apparent. With that aim, we designed Multimed, which is a versatile hardware platform for the real-time recording and processing of biosignals. Digital processing in Multimed is an arrangement of generic processing units from a custom library. These can freely be rearranged to match the needs of the application. Embedded onto a Field Programmable Gate Array (FPGA), these modules utilize full-hardware signal processing to lower processing latency. It achieves constant latency, and sub-millisecond processing and decision-making on 64 channels. The FPGA core processing unit makes Multimed suitable as either a reconfigurable electrophysiology system or a prototyping platform for VLSI implantable medical devices. It is specifically designed for open- and closed-loop experiments and provides consistent feedback rules, well within biological microseconds timeframes. This paper presents the specifications and architecture of the Multimed system, then details the biosignal processing algorithms and their digital implementation. Finally, three applications utilizing Multimed in neuroscience and diabetes research are described. They demonstrate the system\u2019s configurability, its multi-channel, real-time processing, and its feedback control capabilities.<\/jats:p>","DOI":"10.3390\/s18072099","type":"journal-article","created":{"date-parts":[[2018,7,2]],"date-time":"2018-07-02T10:56:52Z","timestamp":1530529012000},"page":"2099","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Multimed: An Integrated, Multi-Application Platform for the Real-Time Recording and Sub-Millisecond Processing of Biosignals"],"prefix":"10.3390","volume":"18","author":[{"given":"Antoine","family":"Pirog","sequence":"first","affiliation":[{"name":"Laboratoire de l\u2019Int\u00e9gration du Mat\u00e9riau au Syst\u00e8me (IMS), University of Bordeaux, Bordeaux INP, CNRS UMR 5218, F-33400 Talence, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4758-7227","authenticated-orcid":false,"given":"Yannick","family":"Bornat","sequence":"additional","affiliation":[{"name":"Laboratoire de l\u2019Int\u00e9gration du Mat\u00e9riau au Syst\u00e8me (IMS), University of Bordeaux, Bordeaux INP, CNRS UMR 5218, F-33400 Talence, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romain","family":"Perrier","sequence":"additional","affiliation":[{"name":"Signalisation et physiopathologie cardiovasculaire, INSERM S-1180, University of Paris Sud, F-92296 Ch\u00e2tenay-Malabry, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthieu","family":"Raoux","sequence":"additional","affiliation":[{"name":"Institut de Chimie et Biologie des Membranes et des Nano-objets (CBMN), University of Bordeaux, CNRS UMR 5248, F-33600 Pessac, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manon","family":"Jaffredo","sequence":"additional","affiliation":[{"name":"Institut de Chimie et Biologie des Membranes et des Nano-objets (CBMN), University of Bordeaux, CNRS UMR 5248, F-33600 Pessac, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Quotb","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Analyse et d\u2019Architecture des Syst\u00e8mes (LAAS), Federal University of Toulouse Midi-Pyr\u00e9n\u00e9es, CNRS UMR 8001, F-31031 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6847-5641","authenticated-orcid":false,"given":"Jochen","family":"Lang","sequence":"additional","affiliation":[{"name":"Institut de Chimie et Biologie des Membranes et des Nano-objets (CBMN), University of Bordeaux, CNRS UMR 5248, F-33600 Pessac, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"No\u00eblle","family":"Lewis","sequence":"additional","affiliation":[{"name":"Laboratoire de l\u2019Int\u00e9gration du Mat\u00e9riau au Syst\u00e8me (IMS), University of Bordeaux, Bordeaux INP, CNRS UMR 5218, F-33400 Talence, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5632-7991","authenticated-orcid":false,"given":"Sylvie","family":"Renaud","sequence":"additional","affiliation":[{"name":"Laboratoire de l\u2019Int\u00e9gration du Mat\u00e9riau au Syst\u00e8me (IMS), University of Bordeaux, Bordeaux INP, CNRS UMR 5218, F-33400 Talence, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16093","DOI":"10.1038\/natrevmats.2016.93","article-title":"Neural recording and modulation technologies","volume":"2","author":"Chen","year":"2017","journal-title":"Nat. Rev. Mater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1113\/jphysiol.1981.sp013763","article-title":"Electrophysiology of mammalian inferior olivary neurones in vitro. Different types of voltage-dependent ionic conductances","volume":"315","author":"Yarom","year":"1981","journal-title":"J. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1152\/physrev.1985.65.1.37","article-title":"Current source-density method and application in cat cerebral cortex: Investigation of evoked potentials and EEG phenomena","volume":"65","author":"Mitzdorf","year":"1985","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1007\/s00125-015-3558-z","article-title":"Slow potentials encode intercellular coupling and insulin demand in pancreatic beta cells","volume":"58","author":"Lebreton","year":"2015","journal-title":"Diabetologia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1152\/jn.1996.76.6.3823","article-title":"Variability of extracellular spike waveforms of cortical neurons","volume":"76","author":"Fee","year":"1996","journal-title":"J. Neurophysiol."},{"key":"ref_6","unstructured":"(2018, May 03). National Instruments. Available online: http:\/\/www.ni.com."},{"key":"ref_7","unstructured":"(2018, May 03). Intan Technologies. Available online: http:\/\/www.intantech.com."},{"key":"ref_8","unstructured":"(2018, May 03). Inovation in Electrophysiology. Available online: http:\/\/www.multichannelsystems.com."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.conb.2014.11.004","article-title":"Neural ensemble communities: Open-source approaches to hardware for large-scale electrophysiology","volume":"32","author":"Siegle","year":"2015","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Laxpati, N.G., Mahmoudi, B., Gutekunst, C.A., Newman, J.P., Zeller-Townson, R., and Gross, R.E. (2014). Real-time in vivo optogenetic neuromodulation and multielectrode electrophysiologic recording with NeuroRighter. Front. Neuroeng., 7.","DOI":"10.3389\/fneng.2014.00040"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"045003","DOI":"10.1088\/1741-2552\/aa5eea","article-title":"Open Ephys: An open-source, plugin-based platform for multichannel electrophysiology","volume":"14","author":"Siegle","year":"2017","journal-title":"J. Neural Eng."},{"key":"ref_12","unstructured":"Wagenaar, D., Demarse, T.B., and Potter, S.M. (2005, January 16\u201319). MeaBench: A toolset for multi-electrode data acquisition and on-line analysis. Proceedings of the 2nd International IEEE EMBS Conference on Neural Engineering, Arlington, VA, USA."},{"key":"ref_13","unstructured":"(2018, May 03). ArtE Source Repository. Available online: https:\/\/github.com\/imalsogreg\/arte-ephys."},{"key":"ref_14","unstructured":"L.M.F. and J. MacArthur, Harvard Instrumentation Design Laboratory (2018, June 29). EShop Wiki. Available online: https:\/\/wiki.harvard.edu\/confluence\/display\/ESHOP\/NSpike."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Patel, Y.A., George, A., Dorval, A.D., White, J.A., Christini, D.J., and Butera, R.J. (2017). Hard real-time closed-loop electrophysiology with the Real-Time eXperiment Interface (RTXI). PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005430"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"M\u00fcller, J., Bakkum, D.J., and Hierlemann, A. (2013). Sub-millisecond closed-loop feedback stimulation between arbitrary sets of individual neurons. Front. Neural Circuits, 6.","DOI":"10.3389\/fncir.2012.00121"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"46005","DOI":"10.1088\/1741-2560\/11\/4\/046005","article-title":"Closed-loop optical neural stimulation based on a 32-channel low-noise recording system with online spike sorting","volume":"11","author":"Nguyen","year":"2014","journal-title":"J. Neural Eng."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3389\/fnins.2014.00169","article-title":"A neurochemical closed-loop controller for deep brain stimulation: Toward individualized smart neuromodulation therapies","volume":"8","author":"Grahn","year":"2014","journal-title":"Front. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Thompson, M., Cheran, L.-E., and Sadeghi, S. (2013). Sensor technology in neuroscience. RSC Detection Science, Royal Society of Chemistry.","DOI":"10.1039\/9781849735414"},{"key":"ref_20","unstructured":"Nguyen, Q.V., Caro, A., Raoux, M., Quotb, A., Floderer, J.B., Bornat, Y., Renaud, S., and Lang, J. (2013). A novel bioelectronic glucose sensor to process distinct electrical activities of pancreatic beta-cells. Proc. Annu. Int. Conf. IEEE Eng. Med. Biol. Soc., 172\u2013175."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3389\/fnins.2016.00067","article-title":"Generation of locomotor-like activity in the isolated rat spinal cord using intraspinal electrical microstimulation driven by a digital neuromorphic CPG","volume":"10","author":"Joucla","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fneng.2011.00007","article-title":"Wavelet transform for real-time detection of action potentials in neural signals","volume":"4","author":"Quotb","year":"2011","journal-title":"Front. Neuroeng."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0165-0270(99)00076-X","article-title":"A 100-channel system for real time detection and storage of extracellular spike waveforms","volume":"91","author":"Guillory","year":"1999","journal-title":"J. Neurosci. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1002\/cta.2192","article-title":"Theoretical study and optimisation of a standard deviation estimator circuit for adaptive threshold spike detection","volume":"44","author":"Rummens","year":"2016","journal-title":"Int. J. Circuit Theory Appl."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pirog, A., Bornat, Y., Renaud, S., Perrier, R., Jaffredo, M., Raoux, M., and Lang, J. (2017, January 19\u201321). A versatile electrode sorting module for MEAs: Implementation in a FPGA-based real-time system. Proceedings of the IEEE Biomedical Circuits and Systems Conference (BioCAS 2017 IEEE), Torino, Italy.","DOI":"10.1109\/BIOCAS.2017.8325154"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.snb.2005.04.042","article-title":"A microelectrode array (MEA) integrated with clustering structures for investigating in vitro neurodynamics in confined interconnected sub-populations of neurons","volume":"114","author":"Berdondini","year":"2006","journal-title":"Sens. Actuators B Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.neucom.2004.10.094","article-title":"Burst detection algorithms for the analysis of spatio-temporal patterns in cortical networks of neurons","volume":"65","author":"Chiappalone","year":"2005","journal-title":"Neurocomputing"},{"key":"ref_28","first-page":"173","article-title":"Dynamics and plasticity in developing neuronal networks in vitro","volume":"147","author":"Vajda","year":"2005","journal-title":"Prog. Brain Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/bem.21805","article-title":"In-vitro exposure of neuronal networks to the GSM-1800 signal","volume":"34","author":"Moretti","year":"2013","journal-title":"Bioelectromagnetics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.conb.2010.02.015","article-title":"Beta-band oscillations\u2014Signalling the status quo?","volume":"20","author":"Engel","year":"2010","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1212\/WNL.0b013e3182302056","article-title":"Responsive cortical stimulation for the treatment of medically intractable partial epilepsy","volume":"77","author":"Morrell","year":"2011","journal-title":"Neurology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/ncpneuro0556","article-title":"Technology insight: Future neuroprosthetic therapies for disorders of the nervous system","volume":"3","author":"Normann","year":"2007","journal-title":"Nat. Clin. Pract. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fncir.2013.00040","article-title":"In vitro large-scale experimental and theoretical studies for the realization of bi-directional brain-prostheses","volume":"7","author":"Bonifazi","year":"2013","journal-title":"Front. Neural Circuits"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"275","DOI":"10.3389\/fnins.2016.00275","article-title":"Bio-inspired controller on an FPGA applied to closed-loop diaphragmatic stimulation","volume":"10","author":"Zbrzeski","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zbrzeski, A.M., Siu, R., Bornat, Y., Hillen, B.K., Jung, R., and Renaud, S. (2015, January 22\u201324). A versatile fast-development platform applied to closed-loop diaphragmatic pacing. Proceedings of the 7th International IEEE\/EMBS Conference on Neural Engineering (NER), Montpellier, France.","DOI":"10.1109\/NER.2015.7146742"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/neuro.16.012.2009","article-title":"A low-cost multielectrode system for data acquisition enabling real-time closed-loop processing with rapid recovery from stimulation artifacts","volume":"2","author":"Rolston","year":"2009","journal-title":"Front. Neuroeng."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1109\/TNSRE.2012.2183617","article-title":"Design and Validation of a Fully Implantable, Chronic, Closed-Loop Neuromodulation Device with Concurrent Sensing and Stimulation","volume":"20","author":"Stanslaski","year":"2012","journal-title":"IEEE Trans. Neural Syst. Rehabil. Eng."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1109\/TBCAS.2016.2574362","article-title":"A Fully Integrated Wireless Compressed Sensing Neural Signal Acquisition System for Chronic Recording and Brain Machine Interface","volume":"10","author":"Liu","year":"2016","journal-title":"IEEE Trans. Biomed. Circuits Syst."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3389\/fnins.2013.00215","article-title":"Real-time biomimetic central pattern generators in an FPGA for hybrid experiments","volume":"7","author":"Ambroise","year":"2013","journal-title":"Front. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Castelli, J., K\u00f6lbl, F., Siu, R., N\u2019Kaoua, G., Bornat, Y., Mangalore, A., Hillen, B., Abbas, J.J., Renaud, S., and Jung, R. (2017, January 11\u201315). An IC-based controllable stimulator for respiratory muscle stimulation investigations. Proceedings of the 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Seogwipo, Korea.","DOI":"10.1109\/EMBC.2017.8037236"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.bios.2018.06.015","article-title":"Bioelectronic organ-based sensor for microfluidic real-time analysis of the demand in insulin","volume":"117","author":"Perrier","year":"2018","journal-title":"Biosens. Bioelectron."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/18\/7\/2099\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:10:48Z","timestamp":1760195448000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/18\/7\/2099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,30]]},"references-count":41,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,7]]}},"alternative-id":["s18072099"],"URL":"https:\/\/doi.org\/10.3390\/s18072099","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,30]]}}}