A Nanotechnology-based Biosensor Targeting Salivary Biomarkers to Detect and Monitor Heart Failure
News
Our team won 2 awards!!
1) Outstanding Team Presentation (Midterm)
2) Outstanding Team Presentation (Final)
Research Significance
Congestive heart failure (CHF) is a common disease affecting the aging population and is the leading cause of mortality worldwide despite significant progress in detecting, monitoring, and treating the illness over the last century. CHF is one of the costliest disease syndromes, affecting over 64 million people worldwide [1]. A significant percentage of the high cost of CHF treatments is attributable to frequent visits to medical centers for assessment, which not only represent an economic burden, but they are time consuming and inconvenient, especially for people who live in rural communities where no medical centers are available. As the global population’s average continues to grow, the prevalence of CHF that requires monitoring is projected to increase. Although monitoring of vital signs with blood pressure, temperature, heart rate, weight gain, and laboured breathing at home is possible, unfortunately, due to the indirect nature of those measurements, these monitoring of vital signs may not be able to accurately detect the onsite of the disease at the early stage. Therefore, there is a need to develop alternative and complementary approaches for reliable non-invasive diagnostic and monitoring solutions. Saliva is known to contain many clinical biomarkers specific to cardiovascular diseases, including CHF [2]. In comparison to blood collection, saliva collection is truly non-invasive and is especially appropriate for elderly patients who require repeated collections. Therefore, the significance of this research relies on developing a sustainable technology to monitor saliva biomarkers associated with CHF that can be used at home on a daily basis.
Concept
The overall objective of this research is to develop a non-invasive nanofibrous (NF)-based electrochemical biosensor framework integrated into a mouth guard for long-term, reliable detection of CHF-specific biomarkers from saliva with high sensitivity and specificity for early diagnosis of heart failure. The central idea is that the NFs-based biosensor will provide a reliable way to analyze and detect CHF based on the electrical conductive variability of a specific biomarker concentration of saliva. In overall, the proposed framework includes three major components: a biosensor development, a docking station to facilitate multi-analyte determinations by scanning conductivity sensitive biomarkers, and a mobile application to visualize biosensor data and detect the presence of the target biomarker.The overall objective of this research is to develop a non-invasive nanofibrous (NF)-based electrochemical biosensor framework integrated into a mouth guard for long-term, reliable detection of CHF-specific biomarkers from saliva with high sensitivity and specificity for early diagnosis of heart failure. The central idea is that the NFs-based biosensor will provide a reliable way to analyze and detect CHF based on the electrical conductive variability of a specific biomarker concentration of saliva. In overall, the proposed framework includes three major components: a biosensor development, a docking station to facilitate multi-analyte determinations by scanning conductivity sensitive biomarkers, and a mobile application to visualize biosensor data and detect the presence of the target biomarker.
The Biosensor
Biosensor development. A flexible and conductive membrane was fabricated by combined processes of electrospinning and coating with graphene for better electrical conductivity compared non-coated. The electrospinning technique was used given the feasibility of fabricating a nanofibrous (NFs) hierarchical architecture that provides a unique environment for biosensing due to controlled fluid delivery and retention ability that facilitates direct electron transfer. We tested the membrane for a particular biomarker called (BNP), which is known to be related to CHF, and confirmed its functionality by comparing it with a commercially available BNP biosensor.
Fig 1: Conventional electrospinning set-up to obtain nanofibers B) Macroscope image of nanofibrous mat collected on aluminum foil C) Scanning electron microscope image of the nanofiber membrane formed from polycaprolactone polymer.
Docking station.
We developed a hardware prototype that consists of three main components: (1) conductivity measurement electronic board module, (2) data processing and communication unit and (3) mouth guard docking station hardware module. As a proof of concept, we tested the device by conducting measurements of conductance using increasing amounts of phosphate buffered saline solution, thus confirming the correct functionality.
Biosensor data mobile app. The docking station transmits conductivity data via Bluetooth communication to the mobile app which visualizes the data.
[1] https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142.
[2] Aronson, Jeffrey K., and Robin E. Ferner. "Biomarkers—a general review." Current protocols in pharmacology 76.1 (2017): 9-23.
The Team
Each team member has their own unique expertise but shares common interests in wearables, non-invasive sensors, and remote health condition detection and monitoring. Fig 1 shows the expertise of each team member and the role taken by them to work on the project aim which was independent of each other. Fig 2-5 shows the preliminary results obtained by each team member. Dr. Dubey focused on the development of a flexible and conductive membrane which was fabricated by combined processes of electrospinning and coating with graphene for better electrical conductivity compared with non-coated (Fig 2). Moreover, he tested the BNP biomarker using commercially available biosensors to check the feasibility of using biomarkers as standard for our biosensors (Fig 3). Dr. Penaloza worked on the development of the hardware components of the biosensor to measure the electrochemical signals of a biomarker. As a proof of concept, he tested the conductance (Fig 4) of the developed component using phosphate buffered saline. Dr.Hongwu took charge of what the final device will look like, which will be acceptable to the patients and how it can be used in daily life. Fig 5 shows the device prototype which can be used for preclinical screening in houses and in hospitals by patients and physicians respectively.
Future Work
Although great progress has been achieved, the integration of the current biosensor membrane into a mouth guard that collects saliva is still under development. Moreover, the integration and testing of the membrane-coated mouthguard that attaches to the docking station need to be conducted. In future work, a user acceptability analysis will be conducted to confirm the usability form factor. Finally, a more sophisticated data analysis with machine learning algorithms will be implemented in the mobile app to detect the presence of the target biomarker, and eventually, send a notification to the physician of the user.