The FDA approved the first ingestible sensor (IS) technology in 2015 (1), then in 2019(2), it approved a second sensor variation. This technology records oral medicine adherence. The ability of these medical devices to record distant, real-time data on drug ingestion sometimes along with concurrent physiological data—is a significant achievement (3). These innovative digital technologies may enable continuous treatment adherence support in addition to precise oral dose ingestion confirmation (4). The WHO global strategy states that digital technology will play a role in global health in the future. Global security, health promotion, and the provision of services to the most vulnerable segments of the population can all be enhanced by digitalization (5).  A digital pill is a pharmaceutical dosage form that has an ingestible sensor inside of it. It can also be referred known as a smart pill or an ingestible sensor (6). When it has been consumed, the sensor starts to communicate medical data. Digital medicine includes both the data supplied by the pill's sensor and the technology that goes into making the pill. The sensor's function is to determine whether or not the patient is taking their medication (a method referred to as "compliance")(7). Using ingestible devices is a safe and non-invasive way to access some of the target bodily fluids. This paradigm will make the ability to directly access the gut environment while food is moving through the gastrointestinal (GI) tract. There are many different biomarkers and therapeutic targets that can be assessed since the mucous membrane of the gut facilitates the easy and rapid passage of substances within the gut. Some the interesting substances that are exchanged within the GI tract are enzymes, metabolites, and electrolytes (8).

INGESTIBLE PILL                 

MATERIALS REQUIRED

  Materials required for ingestible sensors are

1. 1. 1. Power supplies
      2. Telecommunication
      3. Microcontrollers and processors
      4. Power switches
      5. Cladding
      6. Sensors

Power Supplies

The power consumption of ingestible devices must be kept low due to the length of operation and the requirement to send data in order to collecting it. Silver-oxide coin batteries are used in a lot of commercially marketed edibles. These batteries have an 8 mm diameter and 2.5 mm thickness and they have a 3 V voltage at about 80 mAh with an acceptable pulsed current of 70 mA. While having a far higher energy density than silver oxide, Li ion batteries are not recommended because of health hazards if they come into contact with stomach fluid. They increase the pH of the stomach liquid if the sealant is removed, which might lead to serious illnesses.

Telecommunication 

Commercial transmitter chips are frequently utilized in communications, and in order to protect patient privacy, data encoding is suggested. Furthermore, recent efforts have been made to increase the transfer carrier frequency in order to enhance data rate transmission (9).

 Microcontrollers and Processors  

The job of transferring commands to and from sensors and transmitters falls to microcontrollers and processor units. They play a considerably bigger role in camera capsules since they have to compress the images in order to use the bandwidth efficiently and convey the data safely. Custom designs are possible based on the requirements.

Power Switches

The ingestible devices typically turned on before use employing magnetic sensing switches.

Cladding

Ingesting electronic devices must have claddings built of materials that are both biocompatible and able to survive the severe environments of the gastrointestinal tract (10).

Sensors

The main elements defining the operation of the ingestible electronic capsule are the sensors, which are used to detect either chemical or physical aspects. The many ingestible sensing capsules that use various kinds of sensors and their driver unit will be covered in more detail when the technologies are discussed in the Application section (11).

MECHANISM

SENSING TARGETS

ORAL CAVITY

Medical professionals visually inspect the oral cavity in order to look for lesions, ulcers, cold sores, cuts, and/or inflammation. For diagnostic purposes, the mouth provides the easiest and most invasive access to biological fluids released, and saliva is typically used to collect DNA samples (12).

OESOPHAGUS

Various imaging capsules, optical coherence tomography, and endoscopic systems have been developed to evaluate the presence of inflammation and lacerations in the esophageal wall, as it is a very important tissue. In addition, the mucosa of the esophageal is observed in order to diagnose conditions where the mucosa's quality could indicate issues such eosinophilic esophagitis (13).

STOMACH

The balance of the stomach juice is essential. It is crucial to keep an eye on several key factors in the stomach, including pH, metabolite concentrations, enzyme synthesis, and the production of electrolytes like bicarbonate. Checking the mucosa's quality visually is essential while looking for stomach ulcers and other conditions. Finding bacteria like Helicobacter pylori, the cause behind ulcers, is an essential phase in the medical diagnostic process (14).

SMALL INTESTINE

Electrolyte, gas, and metabolite balances are useful indications to evaluate the activity of each specific small intestinal segment. Imaging helps determine the integrity of the mucosa and whether there are some lacerations or inflammations. The microbial community of an individual's small intestine can be better understood by the use of taxonomic profiling and bacterial counts (15).

COLON

The results of this research can be used to diagnose a variety of issues, which includes as infections (caused by bacteria, viruses, or parasites), insufficient nutrient absorption, and in serious cases, cancer. It is possible to look for blood traces in the colonic material in addition to lipids, proteins, and fibers. The colon's electrolyte breakdown plays an important part in deciding how well it works. Colonoscopies are an essential tool to inspect the mucosa of the colon and looking for lesions and inflammation. Along with other metabolites, the three major SFCAs butyrate, acetate, and propionate are significant indicators of the colon's health. The study and sequencing of this region's micro biome genes are becoming more and more important for treating various health issues, especially in connection with the idea of leaky colon (16).

TEMPERATURE SENSING CAPSULES

Ingesting temperature sensors are frequently used to measure body temperature in order to assess heat stress in patients, industrial personnel, and maybe even soldiers in the field. Thermostat-based temperature sensors are found in capsules like Vital Sense's CorTemp (23 mm in length, 8.6 mm in diameter), which are manufactured by Mini Mitter Co., Inc and are used to detect core body temperature. Recently, temperature sensors have been incorporated into the majority of newly manufactured products (17).

MEDICATION MONITERING PILLS    

The Proteus Digital drug intake tracking tablet is a relatively recent addition to the market. This pill tracks the quantity consumed and serves as a reminder or signal to consumers that their medication has to be taken. The Proteus pills are not active unless they come into contact with acidic electrolyte. Once this happens, they send a signal to a small body patch that is powered by batteries. The data is then sent via Bluetooth to a nearby Smartphone (18).

PH MONITORING SYSTEM

As HCl is secreted into the stomach, the gastric juice is extremely acidic. The transit of the capsule into the alkaline duodenum is indicated by a sudden pH rise (>3 pH units) from the gastric baseline. The sudden decrease in pH of one or more pH units is commonly used to identify the ileocecal junction, or the point where the ileum and colon meet. Early in 2010, Given Imaging Inc. purchased the Bravo pH monitoring system. The test is carried out while the patients continue with their regular daily activities and diets. The capsule lifetime is typically several days. As the gold standard for monitoring stomach reflux, pH testing are now more widely accepted, assisting medical professionals in the diagnosis and treatment of gastro esophageal reflux disease (GERD).  Functional nonnuclear dyspepsia, colonic diseases, and small bowel dysfunctions are among the other conditions that can be diagnosed using the pH detecting capsules(19).

PH MONITORING SYSTEM

INGESTIBLE SENSORS  SAFETY AND RETENTION