(Invited) Cavitas Sensors: Non-Invasive Bio/Chemical Sensing in Human Body Cavities for Medical and Healthcare
Authors: Mitsubayashi Kohji 
Published: July 2021

Introduction

A non-invasive monitoring is important not only for medical inspection in hospitals but also healthcare management in daily life. For 30 years, we have developed several types of detachable sensors into human cavitas sites (conjunctiva, pharyngeal, oral cavity, etc.) with biocompatible materials and harmless device-techniques (Fig. 1). “Cavitas sensors” attached to body cavities such as a contact lens type and a mouthguard (“no implantable”, “no wearable”) are attracted attention for preventive medicine [1]. In this contribution, the cavitas sensors (soft contact-lens [SCL] and mouthguard [MG] biosensors) in human body cavities will be introduced as novel non-invasive biosensing devices.

Soft contact lens type glucose sensor

The soft contact lens type biosensor was designed for continuous glucose monitoring in tear fluids (Fig. 2) [2]. Biocom-patible poly(MPC-co-PMEH) (PMEH) (Fig. 3) [3,4] and polydimethyl siloxane (PDMS) were employed as the biosensor material. The biosensor consists of a ﬂexible Pt working electrode and an Ag/AgCl reference/counter electrode, which were formed by micro-electro-mechanical systems (MEMS) technique. Glucose oxidase (GOD) was immobilized on the sensitive area by entrapping with PMEH polymer. The contact lens biosensor showed a good relationship between the output current and glucose concentration in a range of 0.03–5.0 mM, covering the reported tear glucose concentrations in normal and diabetic patients. Also, the biosensor was applied to a rabbit for the purpose of tear glucose monitoring. The basal tear glucose was estimated to 0.14 mM. Also, the change of tear glucose induced by the change of blood sugar level was assessed by the oral glucose tolerance test. As a result, tear glucose level increased with a delay of few min from blood sugar level (Fig. 4). The result showed that the contact lens biosensor is expected to provide further detailed information about the relationship between dynamics of blood glucose and tear glucose.

Invisible Mouth guard type sensors with BLE transmitter

The telemetric mouthguard-biosensor was developed with dental materials integrated with Bluetooth low energy (BLE) wireless module for measurement of saliva glucose [5]. The electrodes were formed on the thinner mouthguard surface which made of a polyethylene terephthalate glycol (PETG) using the same method as the contact lens one (Fig. 5). The BLE module, small potentiostat and battery were mounted and heat-sealed between upper and lower mouth guards. In the investigation of in-vitro characterization, the transparent biosensor showed excellent relationship between the output current and the glucose concentration (Fig. 6). In artificial saliva consisting of salts and proteins, the glucose sensor exhibits high-sensitive detection in a range of 5-1000 µmol/L including glucose concentration of human saliva. We demonstrated the capability of the sensor and wireless communication module to characterize an inclusion in oral phantom that imitative structure of human oral cavity. Stable and long-term monitoring (more than 1 day) using telemetry system was established. Monitoring of real-time changes of glucose concentration in artificial saliva with evaluation system of phantom jaw was demonstrated. The mouthguard device would be useful not only for monitoring of the oral chemical and physical information but also for unconstrained controlling of external device and system [6].

Future potential of cavitas sensors

The self-detachable cavitas sensors are expected to allow the non-invasive bio/chemical monitoring, thus improving quality of life in view of the aging of society in near future.

References

[1] K. Mitsubayashi, T. Arakawa, Cavitas Sensors:Contact Lens Type Sensors & Mouthguard Sensors, Electroanalysis, 28(6), 1170-1187, 2016. (10.1002/elan.201600083)
[2] K. Mitsubayashi, Cavitas Biosensors: Noninvasive Approaches to Blood Glucose Monitoring for Diabetes Mellitus, Sensors and Materials, 30(10), 2313–2320, 2018. (10.18494/SAM.2018.2011)
[3] S. Iguchi, H. Kudo, T. Saito, M. Ogawa, H. Saito, K. Otsuka, A. Funakubo, K. Mitsubayashi, A flexible and wearable biosensor for tear glucose measurement, Biomedical Microdevices, 9, 4, pp.603-609, 2007
[4] M.X. Chu, K. Miyajima, D. Takahashi, T. Arakawa, K. Sano, S. Sawada, H. Kudo, Y. Iwasaki, K. Akiyoshi, M. Mochizuki, K. Mitsubayashi, “Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment”, Talanta 83, 960–965, 2011. (10.1016/j.talanta.2010.10.055)
[5] Arakawa T, Kuroki Y, Nitta H, Chouhan P, Toma K, Sawada S, Takeuchi S, Sekita T, Akiyoshi K, Minakuchi S, Mitsubayashi K, Mouthguard biosensor with telemetry system for monitoring of saliva glucose: A novel cavitas sensor, Biosens Bioelectron, 84, 106-111, 2016. doi:10.1016/j.bios.2015.12.014.
[6] Toma K, Tomoto K, Yokota K, Yasuda N, Ishikawa T, Arakawa T, Mitsubayashi K, Mouthguard controller for unconstrained controlling of external devices. Sensors and Materials, 30, 3053-3060, 2018. (10.18494/SAM.2018.2014)

Figure 1