Development of Wearable Biosensors for Continuous Monitoring of Neurological Biomarkers

Kashfia Haque ^1*, Ajeet Kaushik ²

This review discussed the continuous monitoring of neurological biomarkers via wearable biosensors offers early disease detection, personalized treatment, and enhanced patient outcomes, revolutionizing neurology.

Abstract

The field of wearable biosensors has witnessed remarkable advancements in recent years, revolutionizing healthcare by enabling continuous monitoring of various physiological parameters. Among the many applications, the monitoring of neurological biomarkers stands out as a critical area of research and development. This review article provides a comprehensive overview of the progress made in the development of wearable biosensors for continuous monitoring of neurological biomarkers. We discuss the significance of monitoring neurological biomarkers, explore the key challenges faced in this domain, and highlight the emerging technologies and strategies that have paved the way for innovative solutions. Moreover, we delve into the potential clinical applications and future prospects of wearable biosensors in the field of neurology.

Keywords: Neurological Biomarkers, Wearable Biosensors, Continuous Monitoring, Neurological Disorders, Advancements

{YourSignificance}
{Correspondence}

References

Aaron Asael Smith, Rui Li & Zion Tsz Ho Tse,  “Reshaping Healthcare With Wearable Biosensors.” Scientific Reports, vol. 13, no. 1, Nature Portfolio, Mar. 2023, https://doi.org/10.1038/s41598-022-26951-z.

Abubeker, K. M., and S. Baskar. “Internet of Things Based Real-Time Hyperglycemia and Hypoglycemia Monitoring Using Wearable Biosensors.” 2022 International Conference on Electronics and Renewable Systems (ICEARS), Mar. 2022, https://doi.org/10.1109/icears53579.2022.9751878. 

Adam, Tijjani, et al. “Current Advances in Nanomaterial-associated Micro- and Nano-devices for SARS-CoV-2 Detection.” Current Nanoscience, vol. 19, no. 6, Bentham Science Publishers, Nov. 2023, pp. 783–802. https://doi.org/10.2174/1573413719666230124144535.

Albert, Marilyn, et al. “The Diagnosis of Mild Cognitive Impairment Due to Alzheimer’s Disease: Recommendations From the National Institute on Aging-Alzheimer’s Association Workgroups on Diagnostic Guidelines for Alzheimer’s Disease.” Alzheimers & Dementia, vol. 7, no. 3, Elsevier BV, Apr. 2011, pp. 270–79. https://doi.org/10.1016/j.jalz.2011.03.008. 

Avni A. Argun, Muhit Rana. (2022), Point-of-care (POC) assay to detect dengue exposure, Biosensors and Nanotheranostics, 1(1)

Ban, Seunghyeb, et al. “Soft Wireless Headband Bioelectronics and Electrooculography for Persistent Human–Machine Interfaces.” ACS Applied Electronic Materials, vol. 5, no. 2, American Chemical Society, Feb. 2023, pp. 877–86. https://doi.org/10.1021/acsaelm.2c01436.

Bartolomucci, Alessandro, et al. “Granins as Disease-biomarkers: Translational Potential for Psychiatric and Neurological Disorders.” Neuroscience, vol. 170, no. 1, Elsevier BV, Sept. 2010, pp. 289–97. https://doi.org/10.1016/j.neuroscience.2010.06.057. 

Bishop, Paul, et al. “Ubiquitin C-terminal Hydrolase L1 (UCH-L1): Structure, Distribution and Roles in Brain Function and Dysfunction.” Biochemical Journal, vol. 473, no. 16, Portland Press, Aug. 2016, pp. 2453–62. https://doi.org/10.1042/bcj20160082. 

Boggs, Joan M. “Myelin Basic Protein: A Multifunctional Protein.” Cellular and Molecular Life Sciences, vol. 63, no. 17, Birkhäuser, June 2006, pp. 1945–61. https://doi.org/10.1007/s00018-006-6094-7. 

Buée, Luc, et al. “Tau Protein Isoforms, Phosphorylation and Role in Neurodegenerative disorders.” Brain Research Reviews, vol. 33, no. 1, Elsevier BV, Aug. 2000, pp. 95–130. https://doi.org/10.1016/s0165-0173(00)00019-9. 

Chandrashekar, Pooja. “Do mental health mobile apps work: Evidence and recommendations for designing high-efficacy mental health mobile apps.” mHealth, vol. 4, 2018, pp. 6–6, https://doi.org/10.21037/mhealth.2018.03.02. 

Chaves, A.R. et al. (2021) ‘Probing the brain–body connection using transcranial magnetic stimulation (TMS): Validating a promising tool to provide biomarkers of neuroplasticity and central nervous system function’, Brain Sciences, 11(3), p. 384. doi:10.3390/brainsci11030384. 

Curatolo, Paolo, et al. “Neurological and Neuropsychiatric Aspects of Tuberous Sclerosis Complex.” Lancet Neurology, vol. 14, no. 7, Elsevier BV, July 2015, pp. 733–45. https://doi.org/10.1016/s1474-4422(15)00069-1.

De Leon, Mony J., et al. “MRI And CSF Studies in the Early Diagnosis of Alzheimer’s Disease.” Journal of Internal Medicine, vol. 256, no. 3, Sept. 2004, pp. 205–23. https://doi.org/10.1111/j.1365-2796.2004.01381.x.

De Mello Rieder, Marcelo, et al. “Serum Biomarkers and Clinical Outcomes in Traumatic Spinal Cord Injury: Prospective Cohort Study.” World Neurosurgery, vol. 122, Elsevier BV, Feb. 2019, pp. e1028–36. https://doi.org/10.1016/j.wneu.2018.10.206. 

Ehrenthal, Johannes C., and Cord Benecke. “Tailored Treatment Planning for Individuals With Personality Disorders.” Elsevier eBooks, Jan. 2019, pp. 291–314. https://doi.org/10.1016/b978-0-12-813521-1.00015-1.

Erkkinen, Michael G., et al. “Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases.” Cold Spring Harbor Perspectives in Biology, vol. 10, no. 4, Cold Spring Harbor Laboratory Press, July 2017, p. a033118. https://doi.org/10.1101/cshperspect.a033118.

Frey, Lewis J. “Data Integration Strategies for predictive analytics in Precision Medicine.” Personalized Medicine, vol. 15, no. 6, 2018, pp. 543–551, https://doi.org/10.2217/pme-2018-0035.

Gaetani, Lorenzo, et al. “Neurofilament Light Chain as a Biomarker in Neurological Disorders.” Journal of Neurology, Neurosurgery, and Psychiatry, vol. 90, no. 8, BMJ, Apr. 2019, pp. 870–81. https://doi.org/10.1136/jnnp-2018-320106. 

Gao, Wei, et al. “Fully Integrated Wearable Sensor Arrays for Multiplexed in Situ Perspiration Analysis.” Nature, vol. 529, no. 7587, Nature Portfolio, Jan. 2016, pp. 509–14. https://doi.org/10.1038/nature16521. 

Goedert, Michel. “Alpha-synuclein and Neurodegenerative Diseases.” Nature Reviews Neuroscience, vol. 2, no. 7, Nature Portfolio, July 2001, pp. 492–501. https://doi.org/10.1038/35081564. 

Gold, Larry, et al. “Aptamer-Based Multiplexed Proteomic Technology for Biomarker Discovery.” PLOS ONE, vol. 5, no. 12, Public Library of Science, Dec. 2010, p. e15004. https://doi.org/10.1371/journal.pone.0015004. 

Ha, Minjeong, et al. “Wearable and Flexible Sensors for User-interactive Health-monitoring Devices.” Journal of Materials Chemistry B, vol. 6, no. 24, Royal Society of Chemistry, Jan. 2018, pp. 4043–64. https://doi.org/10.1039/c8tb01063c.

Iqbal, S. M., et al. “Advances in Healthcare Wearable Devices.” Npj Flexible Electronics, vol. 5, no. 1, https://doi.org/10.1038/s41528-021-00107-x.

Janghorban, Mohammad, et al. “Recent Advances, Opportunities, and Challenges in Developing Nucleic Acid Integrated Wearable Biosensors for Expanding the Capabilities of Wearable Technologies in Health Monitoring.” Biosensors, vol. 12, no. 11, Multidisciplinary Digital Publishing Institute, Nov. 2022, p. 986. https://doi.org/10.3390/bios12110986. 

Janssen, John C., et al. “The Prevalence of Oligoclonal Bands in the CSF of Patients With Primary Neurodegenerative Dementia.” Journal of Neurology, vol. 251, no. 2, Springer Science+Business Media, Feb. 2004, pp. 184–88. https://doi.org/10.1007/s00415-004-0296-4.

Jiang, Dawei, and Guozhen Shi. “Research on Data Security and Privacy Protection of Wearable Equipment in Healthcare.” Journal of Healthcare Engineering, vol. 2021, Hindawi Publishing Corporation, Feb. 2021, pp. 1–7. https://doi.org/10.1155/2021/6656204. 

Jönsson, Henrik, et al. “S100B as a Predictor of Size and Outcome of Stroke After Cardiac Surgery.” The Annals of Thoracic Surgery, vol. 71, no. 5, Elsevier BV, May 2001, pp. 1433–37. https://doi.org/10.1016/s0003-4975(00)02612-6. 

Khalil, Michael, et al. “Neurofilaments as Biomarkers in Neurological Disorders.” Nature Reviews Neurology, vol. 14, no. 10, Nature Portfolio, Aug. 2018, pp. 577–89. https://doi.org/10.1038/s41582-018-0058-z. 

Kim, Bokkyu, and Carolee J. Winstein. “Can Neurological Biomarkers of Brain Impairment Be Used to Predict Poststroke Motor Recovery? A Systematic Review.” Neurorehabilitation and Neural Repair, vol. 31, no. 1, SAGE Publishing, Aug. 2016, pp. 3–24. https://doi.org/10.1177/1545968316662708. 

Kim, Dawon, and Yosoon Choi. “Applications of Smart Glasses in Applied Sciences: A Systematic Review.” Applied Sciences, vol. 11, no. 11, Multidisciplinary Digital Publishing Institute, May 2021, p. 4956. https://doi.org/10.3390/app11114956. 

Kim, Heena, et al. “Recent advances in multiplexed wearable sensor platforms for real-time monitoring Lifetime stress: A review.” Biosensors, vol. 13, no. 4, 2023, p. 470, https://doi.org/10.3390/bios13040470. 

Kivirand, Kairi, et al. “Calibrating Biosensors in Flow-Through Set-Ups: Studies With Glucose Optrodes.” InTech eBooks, 2013, https://doi.org/10.5772/54127. 

Krauhausen, Imke, et al. “Brain-Inspired Organic Electronics: Merging Neuromorphic Computing and Bioelectronics Using Conductive Polymers.” Advanced Functional Materials, Wiley-Blackwell, Oct. 2023, https://doi.org/10.1002/adfm.202307729.

Kuhn, Christopher B., et al. “Improving multimodal object detection with individual sensor monitoring.” 2022 IEEE International Symposium on Multimedia (ISM), 2022, https://doi.org/10.1109/ism55400.2022.00022. 

Laaraibi, Abdo-Rahmane Anas, et al. “An Innovative Wearable Sensing System Based on Flexible Piezoresistive Sensors to Estimate Upper Body Joint Angle Using a Nonlinear AutoRegressive Exogenous Neural Model.” IEEE Sensors Journal, vol. 23, no. 21, IEEE Sensors Council, Nov. 2023, pp. 26539–50. https://doi.org/10.1109/jsen.2023.3319559.

Lázaro, Antonio, et al. “Recent Advances in Batteryless NFC Sensors for Chemical Sensing and Biosensing.” Biosensors, vol. 13, no. 8, Multidisciplinary Digital Publishing Institute, July 2023, p. 775. https://doi.org/10.3390/bios13080775.

Li, Shihua. “Huntingtin–protein Interactions and the Pathogenesis of Huntington’s Disease.” Trends in Genetics, vol. 20, no. 3, Elsevier BV, Mar. 2004, pp. 146–54. https://doi.org/10.1016/j.tig.2004.01.008. 

Lin, Wenzhou, et al. “Study on Human Motion Energy Harvesting Devices: A Review.” Machines, vol. 11, no. 10, Multidisciplinary Digital Publishing Institute, Oct. 2023, p. 977. https://doi.org/10.3390/machines11100977.

Lleó, Alberto. “Biomarkers in Neurological Disorders: A Fast-growing Market.” Brain Communications, vol. 3, no. 2, Oxford UP, Apr. 2021, https://doi.org/10.1093/braincomms/fcab086.

Mathew, Minu, et al. “Flexible and Wearable Electrochemical Biosensors Based on Two-dimensional Materials: Recent Developments.” Analytical and Bioanalytical Chemistry, vol. 413, no. 3, Springer Science+Business Media, Oct. 2020, pp. 727–62. https://doi.org/10.1007/s00216-020-03002-y. 

McCutcheon, Robert, et al. “Dopamine and Glutamate in Schizophrenia: Biology, Symptoms and Treatment.” World Psychiatry, vol. 19, no. 1, Wiley-Blackwell, Jan. 2020, pp. 15–33. https://doi.org/10.1002/wps.20693. 

Meschia, James F., et al. “Management of Inherited CNS Small Vessel Diseases: The CADASIL Example: A Scientific Statement From the American Heart Association.” Stroke, vol. 54, no. 10, Lippincott Williams and Wilkins, Oct. 2023, https://doi.org/10.1161/str.0000000000000444. 

Mishra, Saurav. “Artificial Intelligence: A Review of Progress and Prospects in Medicine and Healthcare.” Journal of Electronics, Electromedical Engineering, and Medical Informatics, vol. 4, no. 1, Jan. 2022, pp. 1–23. https://doi.org/10.35882/jeeemi.v4i1.1. 

Modvig, Signe, et al. “Cerebrospinal Fluid Levels of Chitinase 3-like 1 and Neurofilament Light Chain Predict Multiple Sclerosis Development and Disability After Optic Neuritis.” Multiple Sclerosis Journal, vol. 21, no. 14, SAGE Publishing, Feb. 2015, pp. 1761–70. https://doi.org/10.1177/1352458515574148. 

Mohanad, Marwa, et al. “Neuroprotective Effects of Vitamin D in an Alzheimer’s Disease Rat Model: Improvement of Mitochondrial Dysfunction via Calcium/Calmodulin-dependent Protein Kinase Kinase 2 Activation of Sirtuin1 Phosphorylation.” Biofactors, Wiley-Blackwell, Oct. 2023, https://doi.org/10.1002/biof.2013. 

Moshé, Solomon L., et al. “Epilepsy: New Advances.” The Lancet, vol. 385, no. 9971, Elsevier BV, Mar. 2015, pp. 884–98. https://doi.org/10.1016/s0140-6736(14)60456-6. 

Nam, Dahyun, et al. “Next-Generation Wearable Biosensors Developed With Flexible Bio-Chips.” Micromachines, vol. 12, no. 1, Multidisciplinary Digital Publishing Institute, Jan. 2021, p. 64. https://doi.org/10.3390/mi12010064. 

Nisar, Sabah, et al. “Non-invasive Biomarkers for Monitoring the Immunotherapeutic Response to Cancer.” Journal of Translational Medicine, vol. 18, no. 1, BioMed Central, Dec. 2020, https://doi.org/10.1186/s12967-020-02656-7. 

Nutma, Erik, et al. “Translocator Protein Is a Marker of Activated Microglia in Rodent Models but Not Human Neurodegenerative Diseases.” Nature Communications, vol. 14, no. 1, Nature Portfolio, Aug. 2023, https://doi.org/10.1038/s41467-023-40937-z. 

Papa, Linda, et al. “Systematic Review of Clinical Studies Examining Biomarkers of Brain Injury in Athletes After Sports-Related Concussion.” Journal of Neurotrauma, vol. 32, no. 10, Mary Ann Liebert, Inc., May 2015, pp. 661–73. https://doi.org/10.1089/neu.2014.3655. 

Parish, Thomas H., et al. “Development and validation of immunogenicity assays for preclinical and clinical studies.” Ligand-Binding Assays, 2009, pp. 193–238, https://doi.org/10.1002/9780470541517.ch8. 

Prabhakar, Hemanshu, et al. “Chapter 9 - Multimodal Monitoring.” Essentials of Neuroanesthesia, Elsevier, Academic Press, London, United Kingdom, 2017, pp. 161–180. 

Qiu, Shi, et al. “Small Molecule Metabolites: Discovery of Biomarkers and Therapeutic Targets.” Signal Transduction and Targeted Therapy, vol. 8, no. 1, Nature Portfolio, Mar. 2023, https://doi.org/10.1038/s41392-023-01399-3. 

Reiber, Hansotto, and James B. Peter. “Cerebrospinal Fluid Analysis: Disease-related Data Patterns and Evaluation Programs.” Journal of the Neurological Sciences, vol. 184, no. 2, Elsevier BV, Mar. 2001, pp. 101–22. https://doi.org/10.1016/s0022-510x(00)00501-3. 

Rodrigues, Daniela Sofia Sousa, et al. “Skin-Integrated Wearable Systems and Implantable Biosensors: A Comprehensive Review.” Biosensors, vol. 10, no. 7, Multidisciplinary Digital Publishing Institute, July 2020, p. 79. https://doi.org/10.3390/bios10070079. 

Sharma, Atul, et al. “Wearable Biosensors: An Alternative and Practical Approach in Healthcare and Disease Monitoring.” Molecules, vol. 26, no. 3, Multidisciplinary Digital Publishing Institute, Feb. 2021, p. 748. https://doi.org/10.3390/molecules26030748. 

Sheffrin M, Stijacic Cenzer I, Steinman MA. Desire for predictive testing for Alzheimer’s disease and impact on advance care planning: a cross-sectional study. Alzheimers Res Ther. 2016;8(1):55. doi: 10.1186/s13195-016-0223-9. 

Shinozaki, Koichiro, et al. “S-100B and Neuron-specific Enolase as Predictors of Neurological Outcome in Patients After Cardiac Arrest and Return of Spontaneous Circulation: A Systematic Review.” Critical Care, vol. 13, no. 4, BioMed Central, Jan. 2009, p. R121. https://doi.org/10.1186/cc7973. 

Singh, Umesh Pratap. “Decision making and predictive analysis for Real Time Data.” Advances in Data Science and Analytics, 2022, pp. 21–38, https://doi.org/10.1002/9781119792826.ch2. 

Smith, Aaron Asael, et al. “Reshaping Healthcare With Wearable Biosensors.” Scientific Reports, vol. 13, no. 1, Nature Portfolio, Mar. 2023, https://doi.org/10.1038/s41598-022-26951-z. 

Smith, Aaron Asael, et al. “Reshaping healthcare with wearable biosensors.” Scientific Reports, vol. 13, no. 1, 2023, https://doi.org/10.1038/s41598-022-26951-z. 

Soleymani, Leyla, and Feng Li. “Mechanistic challenges and advantages of biosensor miniaturization into the nanoscale.” ACS Sensors, vol. 2, no. 4, 2017, pp. 458–467, https://doi.org/10.1021/acssensors.7b00069. 

Song, Yu, et al. “Self-Powered Wearable Biosensors.” Accounts of Materials Research, vol. 2, no. 3, American Chemical Society, Feb. 2021, pp. 184–97. https://doi.org/10.1021/accountsmr.1c00002. 

Stangler, Luke A., et al. “Microdialysis and Microperfusion Electrodes in Neurologic Disease Monitoring.” Fluids and Barriers of the CNS, vol. 18, no. 1, BioMed Central, Dec. 2021, https://doi.org/10.1186/s12987-021-00292-x. 

Suárez-Calvet, Marc, et al. “sTREM 2 Cerebrospinal Fluid Levels Are a Potential Biomarker for Microglia Activity in Early-stage Alzheimer’s Disease and Associate With Neuronal Injury Markers.” EMBO Molecular Medicine, vol. 8, no. 5, Springer Nature, Mar. 2016, pp. 466–76. https://doi.org/10.15252/emmm.201506123. 

Tettey, Felix, et al. “A Review of Biomedical Devices: Classification, Regulatory Guidelines, Human Factors, Software as a Medical Device, and Cybersecurity.” Biomedical Materials & Devices, Springer Science+Business Media, Aug. 2023, https://doi.org/10.1007/s44174-023-00113-9.  

Thelin, Eric P., et al. “A Review of the Clinical Utility of Serum S100B Protein Levels in the Assessment of Traumatic Brain Injury.” Acta Neurochirurgica, vol. 159, no. 2, Springer Science+Business Media, Dec. 2016, pp. 209–25. https://doi.org/10.1007/s00701-016-3046-3. 

Topol, Eric J. “High-performance Medicine: The Convergence of Human and Artificial Intelligence.” Nature Medicine, vol. 25, no. 1, Nature Portfolio, Jan. 2019, pp. 44–56. https://doi.org/10.1038/s41591-018-0300-7. 

Tripathi, Akhilesh Kumar, et al. “Review of Deep Learning Techniques for Neurological Disorders Detection.” Research Square (Research Square), Research Square (United States), Aug. 2023, https://doi.org/10.21203/rs.3.rs-2269745/v1. 

Van Rensburg, Helena J. Janse, et al. “Circulating Biomarkers for Therapeutic Monitoring of Anti-cancer Agents.” Oncologist, vol. 27, no. 5, AlphaMed Press, Mar. 2022, pp. 352–62. https://doi.org/10.1093/oncolo/oyac047. 

Verma, Deepali, et al. “Internet of Things (IoT) in Nano-integrated Wearable Biosensor Devices for Healthcare Applications.” Biosensors and Bioelectronics: X, vol. 11, Elsevier BV, Sept. 2022, p. 100153. https://doi.org/10.1016/j.biosx.2022.100153. 

Vijayan, Vini, et al. “Review of Wearable Devices and Data Collection Considerations for Connected Health.” Sensors, vol. 21, no. 16, Multidisciplinary Digital Publishing Institute, Aug. 2021, p. 5589. https://doi.org/10.3390/s21165589. 

Vijayan, Vini, et al. “Review of Wearable Devices and Data Collection Considerations for Connected Health.” Sensors, vol. 21, no. 16, Multidisciplinary Digital Publishing Institute, Aug. 2021, p. 5589. https://doi.org/10.3390/s21165589. 

Vos, Pieter E., et al. “GFAP and S100B Are Biomarkers of Traumatic Brain Injury: An Observational Cohort Study.” Neurology, vol. 75, no. 20, Lippincott Williams and Wilkins, Nov. 2010, pp. 1786–93. https://doi.org/10.1212/wnl.0b013e3181fd62d2. 

Wang, Haidong, et al. “Global, Regional, and National Life Expectancy, All-cause Mortality, and Cause-specific Mortality for 249 Causes of Death, 1980–2015: A Systematic Analysis for the Global Burden of Disease Study 2015.” The Lancet, vol. 388, no. 10053, Elsevier BV, Oct. 2016, pp. 1459–544. https://doi.org/10.1016/s0140-6736(16)31012-1. 

Wang, Jiayu, and Jianfei Dong. “Optical Waveguides and Integrated Optical Devices for Medical Diagnosis, Health Monitoring and Light Therapies.” Sensors, vol. 20, no. 14, Multidisciplinary Digital Publishing Institute, July 2020, p. 3981. https://doi.org/10.3390/s20143981. 

Winblad, Bengt, et al. “Mild Cognitive Impairment - Beyond Controversies, Towards a Consensus: Report of the International Working Group on Mild Cognitive Impairment.” Journal of Internal Medicine, vol. 256, no. 3, Wiley-Blackwell, Sept. 2004, pp. 240–46. https://doi.org/10.1111/j.1365-2796.2004.01380.x. 

Woelfle, Tim, et al. “Wearable Sensor Technologies to Assess Motor Functions in People With Multiple Sclerosis: Systematic Scoping Review and Perspective.” Journal of Medical Internet Research, vol. 25, JMIR Publications, July 2023, p. e44428. https://doi.org/10.2196/44428. 

Wunderlich, Michael T., et al. “Neuron-specific Enolase and Tau Protein as Neurobiochemical Markers of Neuronal Damage Are Related to Early Clinical Course and Long-term Outcome in Acute Ischemic Stroke.” Clinical Neurology and Neurosurgery, vol. 108, no. 6, Elsevier BV, Sept. 2006, pp. 558–63. https://doi.org/10.1016/j.clineuro.2005.12.006. 

Zetterberg, Henrik, et al. “Biomarkers of Mild Traumatic Brain Injury in Cerebrospinal Fluid and Blood.” Nature Reviews Neurology, vol. 9, no. 4, Nature Portfolio, Feb. 2013, pp. 201–10. https://doi.org/10.1038/nrneurol.2013.9.