{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T11:10:04Z","timestamp":1782385804265,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-79-10175"],"award-info":[{"award-number":["21-79-10175"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Biosensors based on ion-sensitive field effect transistors (ISFETs) combined with aptamers offer a promising and convenient solution for point-of-care testing applications due to the ability for fast and label-free detection of a wide range of biomarkers. Mobile and easy-to-use readout devices for the ISFET aptasensors would contribute to further development of the field. In this paper, the development of a portable PC-controlled device for detecting aptamer-target interactions using ISFETs is described. The device assembly allows selective modification of individual ISFETs with different oligonucleotides. Ta2O5-gated ISFET structures were optimized to minimize trapped charge and capacitive attenuation. Integrated CMOS readout circuits with linear transfer function were used to minimize the distortion of the original ISFET signal. An external analog signal digitizer with constant voltage and superimposed high-frequency sine wave reference voltage capabilities was designed to increase sensitivity when reading ISFET signals. The device performance was demonstrated with the aptamer-driven detection of troponin I in both reference voltage setting modes. The sine wave reference voltage measurement method reduced the level of drift over time and enabled a lowering of the minimum detectable analyte concentration. In this mode (constant voltage 2.4 V and 10 kHz 0.1Vp-p), the device allowed the detection of troponin I with a limit of detection of 3.27 ng\/mL. Discrimination of acute myocardial infarction was demonstrated with the developed device. The ISFET device provides a platform for the multiplexed detection of different biomarkers in point-of-care testing.<\/jats:p>","DOI":"10.3390\/s24103008","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T10:31:16Z","timestamp":1715250676000},"page":"3008","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Portable Readout System for Biomarker Detection with Aptamer-Modified CMOS ISFET Array"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8051-2425","authenticated-orcid":false,"given":"Dmitriy","family":"Ryazantsev","sequence":"first","affiliation":[{"name":"Scientific-Manufacturing Complex Technological Centre, 1\u20137 Shokin Square, Zelenograd, Moscow 124498, Russia"},{"name":"Institute of Nanotechnology of Microelectronics of the Russian Academy of Sciences, 32A Leninsky Prospekt, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9583-1998","authenticated-orcid":false,"given":"Mark","family":"Shustinskiy","sequence":"additional","affiliation":[{"name":"Institute of Nanotechnology of Microelectronics of the Russian Academy of Sciences, 32A Leninsky Prospekt, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Sheshil","sequence":"additional","affiliation":[{"name":"Scientific-Manufacturing Complex Technological Centre, 1\u20137 Shokin Square, Zelenograd, Moscow 124498, Russia"},{"name":"Institute of Nanotechnology of Microelectronics of the Russian Academy of Sciences, 32A Leninsky Prospekt, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Titov","sequence":"additional","affiliation":[{"name":"Scientific-Manufacturing Complex Technological Centre, 1\u20137 Shokin Square, Zelenograd, Moscow 124498, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9564-5009","authenticated-orcid":false,"given":"Vitaliy","family":"Grudtsov","sequence":"additional","affiliation":[{"name":"Scientific-Manufacturing Complex Technological Centre, 1\u20137 Shokin Square, Zelenograd, Moscow 124498, Russia"},{"name":"Institute of Nanotechnology of Microelectronics of the Russian Academy of Sciences, 32A Leninsky Prospekt, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerii","family":"Vechorko","sequence":"additional","affiliation":[{"name":"Municipal Clinical Hospital No.15 Named after O.M. Filatov, 23 Veshnyakovskaya St, Moscow 111539, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irakli","family":"Kitiashvili","sequence":"additional","affiliation":[{"name":"Municipal Clinical Hospital No.15 Named after O.M. Filatov, 23 Veshnyakovskaya St, Moscow 111539, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3158-4929","authenticated-orcid":false,"given":"Kirill","family":"Puchnin","sequence":"additional","affiliation":[{"name":"Scientific-Manufacturing Complex Technological Centre, 1\u20137 Shokin Square, Zelenograd, Moscow 124498, Russia"},{"name":"Institute of Nanotechnology of Microelectronics of the Russian Academy of Sciences, 32A Leninsky Prospekt, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kuznetsov","sequence":"additional","affiliation":[{"name":"Scientific-Manufacturing Complex Technological Centre, 1\u20137 Shokin Square, Zelenograd, Moscow 124498, Russia"},{"name":"Institute of Nanotechnology of Microelectronics of the Russian Academy of Sciences, 32A Leninsky Prospekt, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6148-0971","authenticated-orcid":false,"given":"Natalia","family":"Komarova","sequence":"additional","affiliation":[{"name":"Scientific-Manufacturing Complex Technological Centre, 1\u20137 Shokin Square, Zelenograd, Moscow 124498, Russia"},{"name":"Institute of Nanotechnology of Microelectronics of the Russian Academy of Sciences, 32A Leninsky Prospekt, Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"130349","DOI":"10.1016\/j.snb.2021.130349","article-title":"New Challenges in Point of Care Electrochemical Detection of Clinical Biomarkers","volume":"345","author":"Campuzano","year":"2021","journal-title":"Sens. Actuators B Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101067","DOI":"10.1016\/j.cpcardiol.2021.101067","article-title":"Troponin I as a Biomarker for Early Detection of Acute Myocardial Infarction","volume":"48","year":"2023","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.amjcard.2009.03.003","article-title":"Frequency of Elevated Troponin I and Diagnosis of Acute Myocardial Infarction","volume":"104","author":"Javed","year":"2009","journal-title":"Am. J. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1515\/cclm-2014-0837","article-title":"Cardiac Troponin Assays: A Review of Quantitative Point-of-Care Devices and Their Efficacy in the Diagnosis of Myocardial Infarction","volume":"53","author":"Amundson","year":"2015","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1136\/emermed-2021-211907","article-title":"Point-of-Care Testing with High-Sensitivity Cardiac Troponin Assays: The Challenges and Opportunities","volume":"39","author":"Cullen","year":"2022","journal-title":"Emerg. Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1039\/D0MA00639D","article-title":"Detection and beyond: Challenges and Advances in Aptamer-Based Biosensors","volume":"1","author":"Yoo","year":"2020","journal-title":"Mater. Adv."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s10404-022-02622-3","article-title":"Aptamer-Based Rapid Diagnosis for Point-of-Care Application","volume":"27","author":"Futane","year":"2023","journal-title":"Microfluid. Nanofluid."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.talanta.2019.02.066","article-title":"Recent Developments of Aptasensors Expedient for Point-of-Care (POC) Diagnostics","volume":"199","author":"Citartan","year":"2019","journal-title":"Talanta"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.biotechadv.2016.02.003","article-title":"Aptamer-Based \u2018Point-of-Care Testing\u2019","volume":"34","author":"Gopinath","year":"2016","journal-title":"Biotechnol. Adv."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Aslan, Y., Atabay, M., Chowdhury, H.K., G\u00f6kt\u00fcrk, I., Saylan, Y., and Inci, F. (2023). Aptamer-Based Point-of-Care Devices: Emerging Technologies and Integration of Computational Methods. Biosensors, 13.","DOI":"10.3390\/bios13050569"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Amen, M.T., Pham, T.T.T., Cheah, E., Tran, D.P., and Thierry, B. (2022). Metal-Oxide FET Biosensor for Point-of-Care Testing: Overview and Perspective. Molecules, 27.","DOI":"10.3390\/molecules27227952"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"116067","DOI":"10.1016\/j.trac.2020.116067","article-title":"Biosensing Based on Field-Effect Transistors (FET): Recent Progress and Challenges","volume":"133","author":"Sadighbayan","year":"2020","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"Q3196","DOI":"10.1149\/2.0291807jss","article-title":"Review\u2014Field-Effect Transistor Biosensing: Devices and Clinical Applications","volume":"7","author":"Syu","year":"2018","journal-title":"ECS J. Solid State Sci. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Thriveni, G., and Ghosh, K. (2022). Advancement and Challenges of Biosensing Using Field Effect Transistors. Biosensors, 12.","DOI":"10.3390\/bios12080647"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/S0956-5663(01)00202-0","article-title":"Development of ISFET Array-Based Microsystems for Bioelectrochemical Measurements of Cell Populations","volume":"16","author":"Martinoia","year":"2001","journal-title":"Biosens. Bioelectron."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1016\/j.bios.2006.11.019","article-title":"Label-Free Detection of Single Nucleotide Polymorphisms Utilizing the Differential Transfer Function of Field-Effect Transistors","volume":"22","author":"Ingebrandt","year":"2007","journal-title":"Biosens. Bioelectron."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6496","DOI":"10.1109\/JSEN.2016.2585920","article-title":"ISFETs in CMOS and Emergent Trends in Instrumentation: A Review","volume":"16","author":"Moser","year":"2016","journal-title":"IEEE Sens. J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shah, S., and Christen, J.B. (2013, January 3\u20136). Pulse Width Modulation Circuit for ISFET Drift Reset. Proceedings of the 2013 IEEE SENSORS, Baltimore, MD, USA.","DOI":"10.1109\/ICSENS.2013.6688269"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1109\/LED.2013.2240648","article-title":"Experimental and Simulated Cycling of ISFET Electric Fields for Drift Reset","volume":"34","author":"Welch","year":"2013","journal-title":"IEEE Electron. Device Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2100163","DOI":"10.1002\/elsa.202100163","article-title":"Recent Advances in Ion-sensitive Field-effect Transistors for Biosensing Applications","volume":"3","author":"Ma","year":"2023","journal-title":"Electrochem. Sci. Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9869","DOI":"10.1021\/acs.analchem.5b02312","article-title":"Electrochemical Aptasensor of Cardiac Troponin I for the Early Diagnosis of Acute Myocardial Infarction","volume":"87","author":"Jo","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_22","first-page":"926","article-title":"Comprehensive Identification of Sensitive and Stable ISFET Sensing Layer High-k Gate Based on ISFET\/Electrolyte Models","volume":"9","author":"Dinar","year":"2019","journal-title":"Int. J. Electr. Comput. Eng."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.snb.2009.09.018","article-title":"ISFET Characteristics in CMOS and Their Application to Weak Inversion Operation","volume":"143","author":"Georgiou","year":"2009","journal-title":"Sens. Actuators B Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.proeng.2017.01.261","article-title":"ISFET-Based Aptasensor for Thrombin Detection Using Horseradish Peroxidase","volume":"174","author":"Andrianova","year":"2017","journal-title":"Procedia Eng."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1109\/JSEN.2018.2881499","article-title":"ISFET Arrays in CMOS: A Head-to-Head Comparison Between Voltage and Current Mode","volume":"19","author":"Miscourides","year":"2019","journal-title":"IEEE Sens. J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ryazantsev, D., Sheshil, A., Grudtsov, V., Rybachek, E., Gabdrakhmanov, A., and Komarova, N. (2023, January 15\u201317). Design of CMOS Readout Circuits for ISFET Aptasensor. Proceedings of the 2023 IEEE Ural-Siberian Conference on Biomedical Engineering, Radioelectronics and Information Technology (USBEREIT), Yekaterinburg, Russia.","DOI":"10.1109\/USBEREIT58508.2023.10158829"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"108387","DOI":"10.1016\/j.mssp.2024.108387","article-title":"A Novel Extended Gate ISFET Design for Biosensing Application Compatible with Standard CMOS","volume":"177","author":"Gubanova","year":"2024","journal-title":"Mater. Sci. Semicond. Process."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"391","DOI":"10.2217\/17435889.2.3.391","article-title":"BioForce Nanosciences, Inc","volume":"2","author":"Henderson","year":"2007","journal-title":"Nanomedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.bios.2019.01.001","article-title":"An Integrated Microfluidic System with Field-Effect-Transistor Sensor Arrays for Detecting Multiple Cardiovascular Biomarkers from Clinical Samples","volume":"129","author":"Sinha","year":"2019","journal-title":"Biosens. Bioelectron."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ijcard.2011.09.077","article-title":"Takotsubo Cardiomyopathy Has a Unique Cardiac Biomarker Profile: NT-ProBNP\/Myoglobin and NT-ProBNP\/Troponin T Ratios for the Differential Diagnosis of Acute Coronary Syndromes and Stress Induced Cardiomyopathy","volume":"154","author":"Schoch","year":"2012","journal-title":"Int. J. Cardiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/clinchem\/45.2.199","article-title":"Simultaneous Rapid Measurement of Whole Blood Myoglobin, Creatine Kinase MB, and Cardiac Troponin I by the Triage Cardiac Panel for Detection of Myocardial Infarction","volume":"45","author":"Apple","year":"1999","journal-title":"Clin. Chem."},{"key":"ref_32","first-page":"16","article-title":"What Is the Best Approximation of Reference Normal for NT-ProBNP? Clinical Levels for Enhanced Assessment of NT-ProBNP (CLEAN)","volume":"2","author":"Bernstein","year":"2011","journal-title":"J. Med. Lab. Diagn."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0196-0644(00)70129-6","article-title":"Diagnostic Accuracy of Myoglobin Concentration for the Early Diagnosis of Acute Myocardial Infarction","volume":"35","author":"Lijmer","year":"2000","journal-title":"Ann. Emerg. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"132146","DOI":"10.1016\/j.colsurfa.2023.132146","article-title":"Comparing Surface Modification Methods for Silicon Nanowire Field-Effect Transistor Biosensors for Diagnosis Applications: A Case Study of Cardiac Troponin I","volume":"676","author":"Vu","year":"2023","journal-title":"Colloids Surf. A Physicochem. Eng. Asp."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"027501","DOI":"10.1149\/1945-7111\/abdde6","article-title":"Polysilicon Field Effect Transistor Biosensor for the Detection of Cardiac Troponin-I (CTnI)","volume":"168","author":"Prajesh","year":"2021","journal-title":"J. Electrochem. Soc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1557\/adv.2020.60","article-title":"Highly Sensitive and Fast Detection of C-Reactive Protein and Troponin Biomarkers Using Liquidgated Single Silicon Nanowire Biosensors","volume":"5","author":"Kutovyi","year":"2020","journal-title":"MRS Adv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1557\/adv.2018.332","article-title":"Highly Sensitive Aptamer-Based Method for the Detection of Cardiac Biomolecules on Silicon Dioxide Surfaces","volume":"3","author":"Hlukhova","year":"2018","journal-title":"MRS Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"223701","DOI":"10.1063\/1.4968593","article-title":"An Effective Electrical Sensing Scheme Using AC Electrothermal Flow on a Biosensor Platform Based on a Carbon Nanotube Network","volume":"109","author":"Lee","year":"2016","journal-title":"Appl. Phys. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"101391","DOI":"10.1016\/j.nantod.2022.101391","article-title":"Highly Performing Graphene-Based Field Effect Transistor for the Differentiation between Mild-Moderate-Severe Myocardial Injury","volume":"43","author":"Rodrigues","year":"2022","journal-title":"Nano Today"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5319","DOI":"10.1007\/s00216-021-03658-0","article-title":"Electrochemical and Electronic Detection of Biomarkers in Serum: A Systematic Comparison Using Aptamer-Functionalized Surfaces","volume":"414","author":"Mishyn","year":"2022","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s11671-023-03886-6","article-title":"Magnetically Controlled Graphene Field-Effect Transistor Biosensor for Highly Sensitive Detection of Cardiac Troponin I","volume":"18","author":"Zhu","year":"2023","journal-title":"Discov. Nano"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"135001","DOI":"10.1016\/j.snb.2023.135001","article-title":"An Electrochemical Metallic Nanowire Aptasensor for Rapid and Ultrasensitive Detection of Cardiac Troponin I","volume":"401","author":"Zhang","year":"2024","journal-title":"Sens. Actuators B Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"20210027","DOI":"10.1002\/EXP.20210027","article-title":"Aptamer-functionalized Field-effect Transistor Biosensors for Disease Diagnosis and Environmental Monitoring","volume":"3","author":"Wang","year":"2023","journal-title":"Exploration"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Vu, C.-A., and Chen, W.-Y. (2019). Field-Effect Transistor Biosensors for Biomedical Applications: Recent Advances and Future Prospects. Sensors, 19.","DOI":"10.3390\/s19194214"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jacc.2009.01.076","article-title":"Incremental Value of Copeptin for Rapid Rule Out of Acute Myocardial Infarction","volume":"54","author":"Reichlin","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_46","first-page":"185","article-title":"Interleukin-6 and High-Sensitivity C-Reactive Protein for the Prediction of Outcomes in Non-ST-Segment Elevation Acute Coronary Syndromes","volume":"66","author":"Lip","year":"2013","journal-title":"Rev. Esp. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.atherosclerosis.2006.06.008","article-title":"Age- and Dose-Dependent Effects of an Eicosapentaenoic Acid-Rich Oil on Cardiovascular Risk Factors in Healthy Male Subjects","volume":"193","author":"Cazzola","year":"2007","journal-title":"Atherosclerosis"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/24\/10\/3008\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:42:51Z","timestamp":1760107371000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/24\/10\/3008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,9]]},"references-count":47,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["s24103008"],"URL":"https:\/\/doi.org\/10.3390\/s24103008","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,9]]}}}