Dental Materials and Biomaterials Program, Integrative Biology and Infectious Diseases Branch, NIDCR
Objective
The goal of this initiative is to develop new prototype biosensors for noninvasive, dynamic, real-time monitoring of physiological processes in the human body using the oral cavity as the sensing site. These biosensors will be able to assess health and disease states and receive signals from oral fluids, cells and microorganisms, as well as other compounds that are found in or pass through the oral cavity. Additional capabilities of such biosensors may include communicating of outputs wirelessly and remotely, and transmitting these outputs to a data collection center or to a drug delivery device that would dynamically and flexibly dispense therapeutic compounds to tissues in accordance with the immediate physiological needs of a patient.
Background
Prevention and early disease detection are key components of maintaining health. In this regard, the ability to have dynamic real-time surveillance and diagnostic information of physiology would have a significant impact. The development of miniature, flexible, and wireless biosensors will provide the opportunity to utilize the oral cavity as a region to gather information on vital physiological, metabolic and toxicological parameters and outputs. In recent years the biosensor field has undergone dramatic expansion (Rogers, 2015 (PDF - 223 KB)). However, one significant hurdle for translating biosensor technologies into clinical practice has been difficulty in finding protected regions on the body where such devices can be safely and easily attached, and where they can be conveniently accessed. In this respect, the oral cavity represents an ideal site as it fulfills these criteria. Moreover, placement of biosensors in the oral cavity can be conveniently performed by dental professionals during routine dental office visits. Lastly, because the oral cavity serves as the entryway for bacteria/viruses, medications, dietary and toxic substances; and offers a choice of soft (cheeks), firm (gingiva), and hard (teeth) surfaces for biosensor placement for short or long-term monitoring (Chengzhou et al., 2014, Hwang et al., 2015), it may become a site of choice for information gathering to enable integrative precision medicine-based diagnostics (Mannoor et al. 2012 (PDF - 807 KB)). For example, recent work demonstrates an oral application of measuring silver and mercury in saliva using a surface-enhanced Raman scattering biosensor taking advantage of plasmonic coupling (Zheng et al. 2015 (PDF - 2,981 KB)). Other work has focused on glucose biosensors using functionalized titanium oxide nanotube arrays (Gao et al., 2014) or surface plasmon resonance optical sensors (Li et al., 2015 (PDF - 1,950 KB)).
Possible applications for dentistry would include detecting changes in the oral flora with respect to caries progression, monitoring the dynamics of periodontal disease, developing and measuring of loading forces during orthodontic treatment, and correlating TMJ loading with the progression from acute to chronic pain in TMD. Beyond dental applications, sensors placed in the oral cavity can monitor changes in the diet, levels of malnutrition, medication intake and compliance, biomolecule turnover, among many other potential measurable inputs. The vision for biosensor research also includes integration of sensing with drug delivery in such a way that a reading of a physiological parameter outside of a predetermined range as detected by a biosensor would transmit a signal to a drug delivery device to dispense a precise dose of a therapeutic compound to restore normal tissue homeostasis. One of many possible examples of such applications could include enabling tight glycemic control for diabetic patients by monitoring blood glucose with oral biosensors and integrating these outputs with insulin from a delivery pump. Another example could be initiating enamel remineralization by the release of calcium- and phosphate- containing nanoparticles in response to a drop in pH, changes in calcium and phosphate levels or an increase in the level of cariogenic bacterial species in the mouth as measured by an oral biosensor.
These and other applications of oral biosensors for dynamic and precise real-time control of oral and systemic diseases and conditions, are likely to generate new therapeutic paradigms for effective, economical and low-morbidity precision medicine approaches that will greatly benefit diverse patient populations.
Feasibility and Timelines
This initiative is feasible and timely because of recent progress in wireless technologies, dissolvable nanotechnology-based electronics, microfabrication technologies and improved sensing and drug delivery instrumentation. The novel biosensors developed as a result of these advances will enable interactive and integrative communication between patients and health care providers, and for certain applications will allow monitoring and program/reprogram treatment remotely (Rogers, 2015 (PDF - 223 KB)). Moreover, since the oral cavity serves as the main entryway for many inputs in the body, this initiative will provide NIDCR a unique opportunity to impact both oral/dental and general health, because these biosensors will have the capacity to obtain, with minimally invasive procedures, real time dynamic monitoring of oral and systemic conditions that can be integrated with dynamic and precise drug delivery to enable precision medicine preventative and therapeutic approaches to improve health.
Current NIDCR/NIH Portfolio
The NIDCR Dental Materials Program currently supports several SBIR/STTR projects through its “Imaging Diagnostics of Dental Diseases and Conditions” FOA (PA12-193 and PA12-195), which are focused on the diagnosis of cracks, dental caries, and measuring pulp vitality with hand held devices that utilize signal inputs and feedback. However, these devices do not employ wireless approach and do not provide continuous, real-time analysis.
Alignment with NIDCR Strategic Plan
Goal 1, Objective 3: Conduct translational and clinical investigations to improve dental, oral, and craniofacial health
Goal 2, Objective 1: Support research toward precise classification, prevention, and treatment of dental, oral, and craniofacial health and disease
NIBIB has shown interest in partnering in this Initiative.
References
Chengzhou Zhu, Guohai Yang, He Li, Dan Du, and Yuehe Lin, Electrochemical Sensors and Biosensors Based on Nanomaterials and Nanostructures, Anal. Chem., 2015 Jan 6;87(1):230-49. doi: 10.1021/ac5039863. Epub 2014 Dec 19.
Gao ZD, Qu Y, Li T, Shrestha NK, Song YY. Development of Amperometric Glucose Biosensor Based on Prussian Blue Functionalized TiO2 Nanotube Arrays. Sci Rep. 2014 Nov 4;4:6891. doi: 10.1038/srep06891.
Li M, Cushing SK, Wu N. Plasmon-enhanced optical sensors: a review. Analyst. 2015 Jan 21;140(2):386- 406. doi: 10.1039/c4an01079e.
Mannoor MS, Tao H, Clayton JD, Sengupta A, Kaplan DL, Naik RR, Verma N, Omenetto FG, McAlpine MC., Graphene-based wireless bacteria detection on tooth enamel. Nat Commun. 2012 Mar 27;3:763. doi: 10.1038/ncomms1767. Erratum in: Nat Commun. 2013;4:1900.
Peng Zheng, Ming Li, Richard Jurevic, Scott K. Cushing, Yuxin Liu, Nianqiang Wu, A gold nanohole array based surface-enhanced Raman scattering biosensor for detection of silver(I) and mercury(II) in human saliva, Nanoscale, 2015, 7, 11005, doi: 10.1039/c5nr02142a.
Rogers JA. Electronics for the human body. JAMA; 2015 Feb 10;313(6):561-2. doi: 10.1001/jama.2014.17915.
Suk-Won Hwang, Chi Hwan Lee, Huanyu Cheng, Jae-Woong Jeong, Seung-Kyun Kang, Jae-Hwan Kim, Jiho Shin, Jian Yang, Zhuangjian Liu, Guillermo A. Ameer, Yonggang Huang, John A. Rogers, Biodegradable Elastomers and Silicon Nanomembranes/ Nanoribbons for Stretchable, Transient Electronics, and Biosensors, Nano Lett. 2015, 15, 2801−2808, doi: 10.1021/nl503997m.