Proteus Digital Health became the first company to receive Food and Drug Administration approval for an ingestible biomedical sensor that monitors the patient’s compliance to medication.
This ‘sensor-enabled tablet’ called Helius comes with an ingestible event marker. It can be administered with pills or incorporated into medicines by the manufacturers. Once swallowed, the sensor is activated by stomach acid. Then, it transmits a signal through the body to the skin patch attached to the skin of a patient, indicating that the patient has ingested medication.
The sensor is designed to measure vital signs for the patient. When ingested by the patient, the stomach acid helps to activate this sensor chip. Information relayed wirelessly back to a smartphone includes the patient’s adherence to the medical regimen and biostatistics including the patient’s heart rate.
The digital signal can only be detected using the adhesive patch attached to the skin like a bandage. It monitors several factors like body posture, temperature, respiration, sleeping patterns and heart rate.
First ingestible medical sensor. Video courtesy of NMANewsDirect. This video demonstrates the functional principle to the ingestible sensor technology introduced by Proteus Digital Health.
The design and development of ingesitble sensors dates back to the early 1960s, when this technology was used for monitoring core temperature of animals and humans. NASA developed an ingestible temperature sensor in 1980s to measure the core temperature of astronauts.
This sensor was later adopted by athletes to monitor the core temperature of the players during games, and wirelessly transmit core body temperature data to trainers on the sidelines.
Research
The utilization of ingestible telemetric sensors for measuring core body temperature in athletic studies of heat strain is becoming increasingly popular. This in turn increases the need for a uniform method to calibrate the sensors to effectively compare the results of different researchers.
Hunt AP et al (2008) from the Queensland University of Technology, Australia, presented a calibration procedure for the ingestible telemetric sensor in 2008.
Three sensors were placed in a water bath for heating at nine discrete temperatures, and the recorded values were compared to that of traceable thermometer values.
Results showed that the recorded temperatures of sensor 2 were higher than sensors 1 and 3. However, all the sensor temperature values were higher than that of the traceable thermometer.
In addition, the experimental results suggested a number of recommendations for a calibration procedure that includes: (1) four water bath temperatures in the range of 33 to 41°C should be utilized; (2) a linear regression that correlates the sensor temperature to a traceable thermometer is an appropriate method for adjusting raw data; (3) sensors should be immersed in the water bath for a minimum of 4 minutes before taking a measurement.
Ingestible telemetric temperature sensors for measuring core temperature (Tc) of the body were described 45 years ago, even though the method is in widespread use for exercise applications only.
Byrne C et al (2007) from the University of Exeter, UK used Bland and Altman’s limits of agreement (LoA) method for quantitatively reviewing the agreement between rectal temperature (Trectal), oesophageal temperature (Toesophageal) and intestinal sensor temperature (Tintestinal) of numerous previously published validation studies.
This team of researchers also reviewed the application of this technology in field-based exercise studies and the factors that may affect. The team concluded that the ingestible telemetric temperature sensor represents a valid index of Tc and exhibits great potential for ambulatory field-based applications.
Recovery of an individual from tuberculosis (TB) is usually hindered due to poor adherence to TB treatment. Directly observed therapy (DOT) is the standard treating technique currently being used. However, high sustaining costs restrict its applications. Therefore, a need for more practical adherence confirmation methods that confirm actual medication ingestions is increasing.
A novel technology recently developed by Belknap R et al (2013) consists of an ingestible sensor and an on-body wearable sensor for electronically confirming unique ingestions and recording the date/time of the ingestion. The company also conducted a feasibility study using an early prototype in active TB patients to determine the accuracy of the system and confirming co-ingestion of TB medications with sensors.
About 30 patients were subjected to 1,080 co-ingestion events and 10 DOT visits. The device showed 95% accuracy and 99.7% specificity based on three false signals recorded by receivers. Hence it was concluded that the system has the potential to correctly identify ingestible sensors and confirm unique ingestions.
Current Applications
The ingestible biomedical sensors are currently being used for treating the following therapeutic areas:
- Hypertension
- Diabetes
- Heart failure
- Mental health
- Tuberculosis.
Future Development
Advances in microelectronics including miniaturization, reduced power consumption, improved efficiency of monolithic system-on-chip (SoC) integration are leading to portable and uninterrupted monitoring in real time under various circumstances.
Although wired epidermic sensors are being and have been widely used in hospitals for a long time, wireless sensors integrated in body area networks provide continuous, minimally obtrusive monitoring in laboratory scenarios. These devices wirelessly transmit data from the body to a base station having secure internet link and rich power supply, and the data can be forwarded to a hospital or anywhere in real time.
In this way, the ingestible sensor developed by Proteus Digital Health can detect ingestions and physiological data by capturing objective information and providing actionable insights. In addition, the company is attempting to develop a pill for monitoring small traces of blood in the lower colon, to screen for bowel cancer.
