{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:21:48Z","timestamp":1760242908981,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2016,10,9]],"date-time":"2016-10-09T00:00:00Z","timestamp":1475971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["16SV3934"],"award-info":[{"award-number":["16SV3934"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Micromachines"],"abstract":"<jats:p>An integration concept for an implantable biosensor for the continuous monitoring of blood sugar levels is presented. The system architecture is based on technical modules used in cardiovascular implants in order to minimize legal certification efforts for its perspective usage in medical applications. The sensor chip operates via the principle of affinity viscometry, which is realized by a fully embedded biomedical microelectromechanical systems (BioMEMS) prepared in 0.25-\u00b5m complementary metal\u2013oxide\u2013semiconductor (CMOS)\/BiCMOS technology. Communication with a base station is established in the 402\u2013405 MHz band used for medical implant communication services (MICS). The implant shall operate within the interstitial tissue, and the hermetical sealing of the electronic system against interaction with the body fluid is established using titanium housing. Only the sensor chip and the antenna are encapsulated in an epoxy header closely connected to the metallic housing. The study demonstrates that biosensor implants for the sensing of low-molecular-weight metabolites in the interstitial may successfully rely on components already established in cardiovascular implantology.<\/jats:p>","DOI":"10.3390\/mi7100183","type":"journal-article","created":{"date-parts":[[2016,10,10]],"date-time":"2016-10-10T10:35:19Z","timestamp":1476095719000},"page":"183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Continuously Operating Biosensor and Its Integration into a Hermetically Sealed Medical Implant"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5818-7379","authenticated-orcid":false,"given":"Mario","family":"Birkholz","sequence":"first","affiliation":[{"name":"IHP, Im Technologiepark 25, 15236 Frankfurt (Oder), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Glogener","sequence":"additional","affiliation":[{"name":"IHP, Im Technologiepark 25, 15236 Frankfurt (Oder), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franziska","family":"Gl\u00f6s","sequence":"additional","affiliation":[{"name":"IHP, Im Technologiepark 25, 15236 Frankfurt (Oder), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Basmer","sequence":"additional","affiliation":[{"name":"IHP, Im Technologiepark 25, 15236 Frankfurt (Oder), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenz","family":"Theuer","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Technical University Berlin, ACK24, Ackerstr. 76, 13355 Berlin, Germany"},{"name":"Acreo Swedish ICT AB, Box 787, SE-60117 Norrk\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,10,9]]},"reference":[{"key":"ref_1","unstructured":"Pfeiffer, D., Szeponik, J., and Gandhi, A. (2008). Technische Systeme f\u00fcr die Lebenswissenschaften, Institut f\u00fcr Bioprozess-und Analysenmesstechnik."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1016\/j.bios.2011.03.009","article-title":"Multi-panel drugs detection in human serum for personalized therapy","volume":"26","author":"Carrara","year":"2011","journal-title":"Biosens. Bioelectron."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1039\/C1CS15134G","article-title":"Cancer detection using nanoparticle-based sensors","volume":"41","author":"Perfezou","year":"2012","journal-title":"Chem. Soc. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1002\/elan.201400073","article-title":"Label-free sensing of biomolecules with field-effect devices for clinical applications","volume":"26","author":"Poghossian","year":"2014","journal-title":"Electroanalysis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1039\/C1LC20693A","article-title":"Highly-integrated lab-on-chip system for point-of-care multiparameter analysis","volume":"12","author":"Schumacher","year":"2012","journal-title":"Lab Chip"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"044113","DOI":"10.1063\/1.4771316","article-title":"Dielectrophoresis based discrimination of human embryonic stem cells from differentiating derivatives","volume":"6","author":"Velugotla","year":"2012","journal-title":"Biomicrofluidics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.bios.2012.05.009","article-title":"A microfluidic-based electrochemical biochip for label-free diffusion-restricted DNA hybridization analysis","volume":"38","author":"Dykstra","year":"2012","journal-title":"Biosens. Bioelectron."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1109\/TPHP.1977.1135193","article-title":"Nonhermeticity of polymeric lid sealants","volume":"13","author":"Traeger","year":"1977","journal-title":"IEEE Trans. Parts Hybrids Packag."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0956-5663(02)00099-4","article-title":"Biosensors for in vivo glucose measurement: Can we cross the experimental stage","volume":"17","author":"Abel","year":"2002","journal-title":"Biosens. Bioelectron."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1016\/j.biomaterials.2007.03.034","article-title":"In vitro, in vivo and post explantation testing of glucose-detecting biosensors: Current methods and recommendations","volume":"28","author":"Koschwanez","year":"2007","journal-title":"Biomaterials"},{"key":"ref_11","unstructured":"Bundesministerium f\u00fcr Bildung und Forschung (BMBF) (2013). Aktionsplan Individualisierte Medizin, BMBF."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1109\/TIM.2013.2253992","article-title":"Fully implantable multi-channel measurement system for acquisition of muscle activity","volume":"62","author":"Lewis","year":"2013","journal-title":"IEEE Trans. Instrum. Meas."},{"key":"ref_13","unstructured":"Glogener, P., Krause, M., Katzer, J., Schubert, M.A., Birkholz, M., Bellmann, O., Weber, C., Hammon, H., Metges, C., and Welsch, C. (2016). Prolonged corrosion stability of a microelectronic biosensor implant during in vivo exposure, submitted."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0956-5663(01)00310-4","article-title":"Sterilization of enzyme glucose sensors: Problems and concepts","volume":"17","author":"Hartmann","year":"2002","journal-title":"Biosens. Bioelectron."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"244904","DOI":"10.1063\/1.4811351","article-title":"Sensing glucose concentrations at GHz frequencies with a fully embedded BioMEMS","volume":"113","author":"Birkholz","year":"2013","journal-title":"J. Appl. Phys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S0142-9612(01)00185-5","article-title":"Biostability of micro-photodiode arrays for subretinal implantation","volume":"23","author":"Kobuch","year":"2002","journal-title":"Biomaterials"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1016\/j.surfcoat.2009.09.075","article-title":"Corrosion-resistant metal layers from a CMOS process for bioelectronic applications","volume":"204","author":"Birkholz","year":"2010","journal-title":"Surf. Coat. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"012022","DOI":"10.1088\/1757-899X\/41\/1\/012022","article-title":"Biostability of an implantable glucose sensor chip","volume":"41","author":"Birkholz","year":"2012","journal-title":"IOP Conf. Ser. Mater. Sci. Eng."},{"key":"ref_19","first-page":"43","article-title":"Systemarchitektur intelligenter sensorimplantate","volume":"55","author":"Basmer","year":"2010","journal-title":"Biomed. Eng.\/Biomed. Tech."},{"key":"ref_20","first-page":"259","article-title":"Energy budget of an implantable glucose measurement system","volume":"57","author":"Basmer","year":"2012","journal-title":"Biomed. Eng.\/Biomed. Tech."},{"key":"ref_21","unstructured":"European Telecommunications Standards Institute (ETSI) (2010). ETSI EN 301 839\u20131 V1.3.1 (2009\u201310), ETSI."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Basmer, T., Todtenberg, N., Popiela, F., and Birkholz, M. (2013, January 9\u201311). Antennas for Medical Implant Applications Operating in the Mics Band. Proceedings of the IEEE MTT-S International Microwave Workshop Series on RF and Wireless Technologies for Biomedical and Healthcare Applications (IMWS-Bio), Singapore.","DOI":"10.1109\/IMWS-BIO.2013.6756194"},{"key":"ref_23","unstructured":"ZL70321\u2014Implantable Radio Module MICS RF Telemetry. Available online: www.microsemi.com\/products\/ultra-low-power-wireless\/implantable-medical-transceivers\/zl70321."},{"key":"ref_24","unstructured":"Knoll, D., Heinemann, B., Barth, R., Blum, K., Borngr\u00e4ber, J., Drews, J., Ehwald, K.-E., Fischer, G., Fox, A., and Grabolla, T. (2004, January 12\u201314). A Modular, Low-Cost SiGe:C BiCMOS Process Featuring High-fT and High-BVceo transistors. Proceedings of the Bipolar\/BiCMOS Circuits and Technology Meeting, Montreal, QC, Canada."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1002\/adfm.201002062","article-title":"Ultrathin TiN membranes as a technology platform for CMOS-integrated MEMS and BioMEMS devices","volume":"21","author":"Birkholz","year":"2011","journal-title":"Adv. Funct. Mater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.mee.2012.04.017","article-title":"Fabrication of MEMS actuators from the BeOL of a 0.25 \u00b5m BiCMOS technology platform","volume":"97","author":"Kulse","year":"2012","journal-title":"Microelectr. Eng."},{"key":"ref_27","first-page":"479","article-title":"Separation of extremely miniaturized medical sensors by IR laser dicing","volume":"12","author":"Birkholz","year":"2010","journal-title":"J. Optoelectron. Adv. Mater."},{"key":"ref_28","unstructured":"Birkholz, M., Ehwald, K.-E., Fr\u00f6hlich, M., Kulse, P., Basmer, T., Ehwald, R., Guschauski, T., Stoll, U., Siegel, H., and Schmaderer, S. (2012). Sensoren und Messsysteme 2012, GMA ITG VDI\/VDE."}],"container-title":["Micromachines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-666X\/7\/10\/183\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:32:34Z","timestamp":1760211154000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-666X\/7\/10\/183"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,9]]},"references-count":28,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2016,10]]}},"alternative-id":["mi7100183"],"URL":"https:\/\/doi.org\/10.3390\/mi7100183","relation":{},"ISSN":["2072-666X"],"issn-type":[{"type":"electronic","value":"2072-666X"}],"subject":[],"published":{"date-parts":[[2016,10,9]]}}}