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Wearable sensors are now a big sector of the wearable electronics market with accelerometers, gyroscopes, magnetometers, and barometers appearing in many common gadgets. Currently, the majority of wearables are based on sensing vital physical parameters including motion and respiration rate and or electrophysiology including ECG and EMG.
However, chemical markers that are relevant to health are being increasingly targeted. So far, wearables operate based on physical sensing of electrical signals, mechanical alterations, and temperature have shown led to strong commercial successes. However, the same success is yet to be seen for chemical sensing. Unfortunately, skin is not easily surmountable and therefore is a natural impediment present against the ultimate chemical sensing for wearable technologies.
Thus far, sweat sensing has shown great promise, 8, 10, but nevertheless, high quality sweat sensing depends on the body temperature and persistent physical activity for inducing it. Several developments tried to overcome this by sensor patches with microspikes for piercing the skin to surpass the epidermis and gain access to the body liquid directly.
The other major category of body monitors and sensors is the family of implantable devices. A noninvasive and safe approach to reach some of the target body fluids is to use ingestible devices. This paradigm will allow for direct access to the gut environment during the passage of ingestibles along the gastrointestinal GI tract. Some of these chemicals of interest that are exchanged inside the GI tract include electrolytes, metabolites, and enzymes.
Progress in ingestible devices benefited from recent advances in sensors and functional materials. These have allowed for the realization of faster sensor response times, increased reliability, higher sensitivity, enhanced selectivity, and with less demand for power. One of the major obstacles for ingestibles in the development has been the power supplies. These have primarily been batteries that had to last for several days during the passage of the ingestible device in the gut.
Fortunately, battery technology has also experienced significant progress in recent years. To date, ingestible sensing capsules can provide information about the internal condition of the gut through images, pH readings, pressure measurements, core temperature data, and also measurement of chemical constituents inside the gut. This Review aims at describing and analyzing the current range technologies that make up ingestible sensor devices. The text depicts the environment of the gut and the potential analytes and variables of interest for sensing.
It presents the different capsule technologies currently being used and researched, discusses them carefully, concludes with the presentation of the future direction of ingestible sensing capsules and pills. Gut Organs and Sensing Targets. The gut is made of distinct organs Figure 1 : the esophagus, stomach, small intestine, and large intestine with the oral cavity mouth as its entrance.
The small intestine itself is made of subsegments that are fundamentally different from one another including the duodenum, jejunum, and ileum. High Resolution Image. To understand the significance and operation of ingestible sensors, it is important to first become familiar with the organs of the GI tract and the chemistry and biology Figure 2 of the GI environment. In this section, the physiology of different organs in the gut is carefully presented and the sensing targets will be discussed.
The first stop for food digestion is the oral cavity. The physical activity of chewing mastication combined with the secretion of enzymes Table 1 and chemicals are the first step to make the food ready for body absorption. Saliva is a bodily fluid formed in the mouth and is of very high physiological importance comprising electrolytes, mucus, white blood cells, epithelial cells, glycoproteins, and enzymes such as amylase and lipase, Table 1 and antimicrobial agents including IgA and lysozyme.
Enzymes released here break down carbohydrates to catalyze them into smaller sugars. Table 1. The mouth is a point of most facile and noninvasive access to the secreted bodily fluid for diagnostics, and DNA samples are generally extracted from saliva. Electrolyte imbalances and disturbances are also obvious targets. The most common clinical targets through saliva testing include hormone disorders, cancer, infectious conditions including HIV and viral hepatitis , and allergy disorders.
The problem of using saliva contents as biomarkers for diagnosis is that the biomarkers are generally present in concentrations that are too low to be analyzed reliably. The esophagus is the connection between the mouth and stomach. Generally, the passage of food through esophagus is quick, in the order of a few seconds, and only minimal food digestion occurs here. However, several significant gut disorders impact this area including acid reflux, from the stomach.
Reflux, in its severe form, can also harm the mouth and deteriorate teeth and gums. The integrity of the esophagus wall is very important, and many imaging capsules, optical coherence tomography, and endoscopy systems have been designed to assess the presence of inflammation and lacerations in this area.
Additionally, the mucosa of the esophagus is monitored for diagnosing disorders where the quality of the mucosa can show signs of problems such as eosinophilic esophagitis. The stomach is a muscular, hollow, dilated organ of the upper part of the gastrointestinal tract Figure 1. The stomach lies under the diaphragm, and positioned behind it is the pancreas. The pancreas has the function of producing the digestive enzymes. The acid HCl that is generated by the gastric glands of the stomach keeps the pH low Figure 3 A , helps with digestion, and also reduces the proliferation of unwanted bacteria from the food.
Glands of the stomach walls Figure 2 secrete digestive enzymes Table 1 and gastric acid for food digestion. The stomach secretes many chemicals and compounds including proteases protein-digesting enzymes including pepsin and other enzymes such as gastric lipase, hormones including gastrin, histamine, endorphins, serotonin, cholecystokinin, and somatostatin , and other chemicals.
Gastric juice is made of 0. There is also the secretion of bicarbonate, a base to buffer the gastric fluid and reduce its acidity when needed. The gastric fluid also contains mucus, as a viscous physical barrier to protect the stomach epithelia in the acidic environment. In the stomach, the food is churned by muscular contractions peristalsis. Some small portion of the food ingested can be absorbed through the stomach mucosa; this includes water, medication of small molecular sizes, selected amino acids, and small concentrations of methanol and caffeine.
The most prevalent stomach disorders include peptic ulcers, gastritis, and stomach cancer, for many of which the cause is the Helicobacter pylori infection. Dietary metabolites such as retinoic acid and aryl hydrocarbon receptor AHR ligands are found in both the stomach and, in much higher concentration, the small intestine. Retinoic acid is a metabolite of vitamin A retinol that mediates the operation of vitamin A which is required for growth and development.
The AHR is a ligand-activated transcription factor involved in the regulation of biological responses to planar aromatic hydrocarbons. AHRs appear in important developmental pathways such as lymphoid systems, T-cells, and neurons. The gastric juice balance is very important. Parameters such as pH, metabolite concentrations, electrolyte production such as bicarbonate , and enzymes are all important parameters to monitor in the stomach.
It is important to visually check the quality of mucosa in the search of stomach ulcer and other disorders. Searching for bacteria such as Helicobacter pylori which is the cause of ulcers is an important medical diagnostic process. The length of the small intestine or otherwise referred to as the small bowel can vary between 3 and 11 m, but on average it is about 6 m, with a diameter of 2.
It is subdivided into three segments: the duodenum, jejunum, and ileum Figure 1. The duodenum is the shortest section of the small intestine which is located in close proximity to the pancreas, gallbladder, and liver Figure 1. The pancreas produces digestive enzymes Table 1 , and the gallbladder generates bile. Bile is a dark green to yellowish brown liquid.
Gallbladder bile consists of bilirubin, fats cholesterol, fatty acids, and lecithin , and inorganic salts. The duodenum secretes hormones that signal the liver and gallbladder to release alkaline bile and digestive enzymes. The duodenum also produces the hormone secretin as a signal for the release of sodium bicarbonate to increase the pH to 7.
Further along the small bowel is the jejunum which is about 2. Small chained sugars, amino acids, and fatty acids are absorbed here. The final segment of the small bowel is the ilium which is about 3 m long, and similarly the mucosa layer contains microvilli where most of the bile acid is absorbed.
These microvilli also allow for very efficient absorption of digested food in this region including fatty acids, small sugar units such as glucose and fructose , and glycerol. Digestive enzymes in the small intestine include those that catalyze proteins such as pepsin , lipids such as lipase , and carbohydrates such as dextrinase and glucoamylase. The microbial community of the small intestine is diverse, and a short list is shown in Figure 1.
Other metabolic byproducts produced from bacteria include different gases dependent on their activities and fermentation of fiber. However, a large volume of such gases are released as flatus. Overgrowth of bacteria, different types of irritable bowel syndrome IBS , malabsorption of carbohydrates, and different types of cancers are among such conditions. Balances of the electrolytes, gases, and metabolites are all valuable parameters for assessing the operation of the each individual segment of the small bowel.
Bacterial counts and taxonomic profiling will help in understanding the microbial community of the small bowel in individuals. The colon starts with the cecum which continues to the ascending colon and then the transverse, descending, and rectum areas and then continues to the anal channel Figure 1. The colonic region is about 1. The colon absorbs water and the final remnants of absorbable nutrients from the processed food intake and then excretes the indigestible matter to the rectum.
Colonic bacterial communities account for over 1. The genome of the colonic bacteria is approximately times larger than the human genome. The bacterial cohort harbors between and prevalent bacterial species, and each individual has at least such species, which are also largely shared between different humans Figure 1. David et al. The three main SCFAs, acetate, propionate, and butyrate, which are produced by the bacterial community of the colon, stimulate colonic sodium and fluid absorption Figure 3 B.
It has been shown that acetate improves colonic blood flow that this in return stimulates the gut motility. Butyrate is the preferred energy substrate for epithelial cells promoting their growth. However, the concentrations of gases are much greater than that in the ileum. Stool colonic content analysis is an important medical diagnostic process. The colonic content may be examined for blood traces as well as the presence of fat, proteins, and fibers.
The breakdown of the electrolytes in the colon is also important in assessing its functionality. Colonoscopies are an important process to assess the quality of the colon mucosa in search for inflammation and wounds. The main three SFCAs of butyrate, acetate, and propionate as well as other metabolites are important chemicals that show the health of the colon.
Gene sequencing of the microbiome of this area and its analysis are becoming increasingly critical for addressing many disorders in the body, especially regarding the concept of leaky colon. General Requirements for Ingestible Devices. There are many factors that are important in the design of ingestible sensing and monitoring capsules.
Critical factors for ingestible devices include: high fidelity and private transmission of data from the capsules to an external receiver; the lifetime of the battery with low power internal electronic circuits; and biocompatibility of the materials used in the capsule.
In this section, the general requirements of ingestible devices for reliable and durable operation will be discussed. Due to the duration of operation and the need to not only gather data but also transmit data, the power consumption of ingestible devices needs to be kept low. Most commercially available ingestibles use silver-oxide coin batteries. Li ion batteries, while having a much higher energy density than that of silver-oxide, are not suitable due to their health and hazard issues if they are exposed to the gastric juice.
If left with no sealant, they increase the pH in the gastric juice which can cause serious illnesses. The small bowel image capsules have a lifetime of up to 8 h, allowing the capsule to reach most of the small intestine region. Wide bandwidth communication is critical for image acquiring capsules that have to process and transmit large amounts of data. Generally, image compressor subsystems are used to limit the data transmission.
For the Given Imaging capsules, the MHz commercial communication band is used and a data rate of 2. It seems that this frequency is also one of the most suitable as the associated electromagnetic waves pass through the body tissues at low propagation loss. There have also been recent efforts in increasing data rate transmission by increasing the transmission carrier frequency.
Microcontrollers and processor units have the responsibility of ordering the commands to and from sensors and transmitters. In camera capsules, they have a much more important role as they are required to compress the images for efficient use of the bandwidth and reliable data transfer. They can be custom designed depending on the requirements. Magnetic reed switches are generally used for turning the ingestible devices on before their use.
The claddings of ingestible electronic devices are required to be made of materials that are biocompatible and remain intact in the caustic environment of the gastrointestinal tract. If chemical sensors are used, then the ingestible device must employ membranes that allow for the target chemical to permeate and for rapid equilibrium to be reached between the environment of the gut and the headspace above the sensors.
The sensors, for sensing either physical or chemical parameters, are the core components that define the operation of the ingestible electronic capsule. The different types of sensors and their driver units, which are used in the various ingestible sensing capsules, will be described in more detail in the Application section when the technologies are described.
Most of the ingestible sensing capsules rely on passive progression in the gut, allowing the body to do the work. There is a strong correlation between the passage of food and capsule in the gut which will be discussed in a later section. However, it is also possible to remotely control the movement of the ingestible device along the GI tract.
Therefore, integrating mechanisms for active locomotion are important. Accurate knowledge of the position and orientation of the capsule when it moves along the GI tract is important to analyze any sensor profiles or images to ensure that the parameters are correctly correlated with the location of the capsule in the gut. This can be based on using permanent magnets, magnetoresistors, or coils embedded in the capsules that respond to an external electric field.
The location can also be based on imaging of absorbed or scattered magnetic waves. Electromagnetic waves at various frequencies ranging from X-rays down to very long wavelengths in radio frequency ranges have been implemented.
Obviously, the hazards of very high wavelengths have to be considered. Ultrasound has also been used for estimating the location of the capsules. As previously discussed Figure 3 A , the environment of the gut generates step changes in the oxygen and pH concentrations. As such, oxygen and pH sensors and the output profiles can be embedded into capsules for accurately identifying the passage from one organ to another.
Capsule retention in healthy users has not been often reported. However, the retention rate is very different in patients with gut disorders. Bowel obstruction due to capsule retention represents the most serious potential adverse event for ingestible devices.
A report from electronic capsule manufacturers shows a retention rate of 0. This is based on 20 prolonged capsule retention events in individual device trials. Capsules are suggested to be not suitable for use in people with pacemakers due to possible mutual interferences. As presented in the previous section, there many physical and chemical entities that can be sensed along the GI tract. There are ingestible sensors that are developed for measuring physical parameters such as core temperature and pressure.
There are chemical and biochemical components that are related to the balances in the gut and the functionalities, but the field is still relatively new with a great prospect for growth. The potential monitored markers include: electrolytes that are responsible to keep the gut environment at the right pH and ionic concentrations; metabolites, including digestion and fermentation metabolites, which play great roles in the function of the body and gastrointestinal tract; enzymes that are the catalysts for digestion and also perform other activities in the gut; and additionally, a large number of microbial communities.
Ingestible sensors can directly measure these components and may also target the byproduct of chemical and biochemical activities such as gases. Ingestible sensors other than image capsules can operate in the normal gut environment while the food or liquid is there to understand normal gut functionality, or they can be stimulated with a specific food substrate to show the impact on the environment or function.
Ingestible sensors may need specific prepreparation before their implementation. For instance, imaging capsules need a gut environment which is cleared of any nontransparent object in advance, requiring the patient to go on a stringent diet for a few days. Mouth Sensors—Stationary Sensing Systems. The first organ to monitor is the mouth. As discussed previously, saliva is the first target media that contains valuable information for sensing, including enzymes and electrolytes.
Saliva sensors can be kept in the mouth for a long duration and then removed. In true evaluation, such sensors may not be considered ingestible as they do not pass through the GI tract, but because they also target the GI tract liquid, they are included in this Review.
Many of the techniques used to analyze the oral phase include sensors mounted onto a mouthguard Figure 4 A platform. It has been shown with this type of technology that they can measure chemicals in the mouth including salivary uric acid 68 and pH. Commercial Ingestible Imaging and Sensing Capsules.
The first report on a swallowable electronic capsule emerged in by Jacobson and Mackay using radiofrequency RF transmission of internal temperature and pressure readings. There is no actual report on the outcomes of using such capsules in humans for decades after it was introduced. The field did not advance much until the early s when the electronic circuits reduced significantly in size and became more prevalent.
In the following sections, the current commercial systems and emerging technologies of ingestible sensors are presented. The focus was initially diverted to endoscopy, and this remains the largest part of the ingestible devices market. The driving factor behind this was to find a method to replace relatively invasive endoscopies based on tube endoscopes that are inserted into the oral or rectal orifices.
Pain, problems with sedation, and potential repeated screening are also other problems. Yoqneam, Israel , based on G. Iddan patents first patent granted in , introduced the wireless capsule endoscopy WCE that incorporated a small camera, LEDs for lighting, transmitter, batteries, and microcontrollers.
Generally, before taking the small intestinal and colon camera capsule, patients are administered with a laxative and are to fast up to 24 h. Additionally, sodium phosphate, prokinetic, and rectal suppository are also prescribed for ensuring an effective lumen cleaning to obtain clean images. The fasting period is 4 h before an esophagus capsule. Here we present a brief description of different camera capsules by Given Imaging Inc. The company is now under the full ownership of Medtronic Fridley, MN.
Given Imaging Inc. The battery life of the capsule is generally in the order of 8—10 h. Due to the short progression time, the esophageal passive capsules require a high frame rate and do not need long battery life. As such, wide angle imaging is required to reduce the chance of going out of focus. This capsule is used today as a complementary tool to traditional colonoscopy. In addition to Given Imaging, there are other companies producing camera capsules with a variety of capabilities Figure 4 C.
This includes endoscopic capsules, such as Olympus Inc. China , MiroCam capsule South Korea. There has been significant progress in video capsule endoscopy in recent years, mainly involving signal processing and computational methods that have been developed to enhance the diagnostic possibilities and improve the accuracy when using camera capsules.
These include algorithms for detecting hemorrhage and lesions, thus reducing the review time for practitioners, localizing the capsule or lesion, assessing intestinal motility, enhancing the video quality, and managing the data. A good review on such techniques can be found in a work by Iakovidis and Koulaouzidis. The ingestible temperature sensors are commonly used for monitoring body temperature mainly to measure heat stress in patients, workers in industrial environments, and also possibly soldiers in the field.
Recently, most of the new ingestible devices have embedded temperature sensors in them. Gastric juice inside the stomach is highly acidic due to the secretion of HCl. The ileocecal junction the junction between the ileum and colon is generally identified as an abrupt pH drop of at least 1 pH unit.
The Bravo system is able to measure pH also temperature and pressure of the GI tract during its passive progression. Recently, pH tests are increasingly being considered as the gold standard for monitoring of gastric reflux, helping clinicians to diagnose and manage gastroesophageal reflux disorders GERD. The passage of the digestible device from the stomach to the small bowel has always been a question. However, it has been shown that there is a very strong relationship between the emptying of a meal to the emptying of the capsule.
Kuo et al. Rao et al. Despite the suggestions that generally the pH capsule should leave the stomach in less than 5 h, transit through the small intestine in less than 6 h, and should transit the colon in less than 60 h, many different scenarios for the capsule transit times have been observed. The timing depends on the body characteristics, the environment, and the degree of body hydration and also more importantly on the food ingested.
Interestingly, fibrous food activates the bacteria in the colon and speeds up its excretion from the colon. Capsules such as the Given Imaging Bravo capsule are also able to obtain pressure profiles of the GI tract. The true values of pressure measurements are still unknown, and more human trials are required. Proper standards should be developed to aid in the identification of various pressure patterns and associations with the gut motility.
A more recent entrance to the market is the medication ingestion monitoring pill by Proteus Digital. The Proteus pills are passive and upon hitting acidic electrolyte are activated, transmitting a signal to a small, battery-powered body patch and sending the data via Bluetooth to possibly a smartphone in the vicinity. The pills are very small, and the actual circuit attached to pill Figure 4 B is only in the order of millimeters in dimension.
Philips Inc. Philips Electronics Inc. The system is able to measure body internal parameters and to deliver a pharmaceutical treatment agent on command, thus also providing a therapeutic functionality to specific target areas. Other Advances in Ingestible Electronic Capsules.
Significant advances have been made regarding ingestible capsule devices that incorporate various gas sensors, wavelength spectrometry, fluorescence and Raman spectroscopy, optical coherence tomography, confocal microendoscopy, electrochemical sensing, and ultrasound imaging units.
A brief overview of such systems will be presented in this section. Gas sensing capsules are one of the newest additions to the ingestible electronic capsules market. Sensing gases as byproducts of the gut activities is a novel idea for monitoring the functionality of the gut Figure 6 A. It has passed stringent animal tests and also the first successful phase of human trials. The capsule has been equipped with oxygen, hydrogen, carbon dioxide, and methane gas sensors Figure 6 B.
Step changes in the oxygen profile associate with the location of the capsule, while other gases are digestive and fermentation gases associated with the gut activities Figure 6 C and D. Gas sensors operate in both aerobic and anaerobic environments and are protected by gas permeable membranes of high integrity.
Some gases of the gut are produced as a result of the endogenous chemical and enzymatic interactions in the gut. The chemical interactions are responsible for changes in the O 2 and CO 2 gas profiles in the stomach Figure 6 C and D. However, the majority of the gas production is associated with fermentation by bacteria in the small intestine jejunum and ileum and colon Figure 6 D.
These bacteria ferment the undigested and unabsorbed food substrates, produce SCFAs, and also produce hydrogen, carbon dioxide, and methane as well as traces of odorous sulfide containing gases such as H 2 S byproducts. These gas sensing capsules are a great replacement for breath test analysis. While the breath test is considered the gold standard for diagnosis of carbohydrate malabsoption, IBS, small intestine overgrowth of bacteria, and many other gut disorders, it still suffers from significant inaccuracies due to reliability on low concentrations of gases measured at the mouth and also interferences from the body metabolism.
Gas sensing capsules measure the gases in the gut at the source point and raise the accuracy of gas measurements and hence can offer higher reliability for diagnosis. Light—tissue interaction can also be exploited for monitoring the health of the gut.
One of the early projects regarding the development of capsules with visible spectroscopy systems was defined under the VECTOR project. The researchers involved in the VECTOR project demonstrated a basic spectroscopic capsule that is able to detect blood in the intestine using transmission based on a LED emission system.
Another recent development was demonstrated by Qiao et al. They used a hue-saturation light color detection method with white LEDs, a membrane that allows the selective penetration of blood cells into the chamber, a color sensitive film, and a color sensor detector. The color sensitive film was made of anion exchange resin that allowed hydrophobic interactions with hemoglobulins and hence the change of color.
The capsule was tested in the lab against different blood concentrations in a buffer, and human trials are yet to be conducted. Very recently, a proof of concept for a fluorescence endoscopy capsule in the — nm range was presented by Demosthenous et al. Figure 7 C. They successfully conducted ex vivo tests in the intestine of swines, although specificity of the system was not demonstrated.
Inoue et al. Reflectance confocal microscopy using quasi-digestible capsules has been successfully shown. Using the broadband nature of optical fibers, these quasi-capsules can acquire very large area confocal images. These systems have been used for detecting eosinophilic esophagitis a disorder which is caused by food allergies, and defined by presence of eosinophil cells in the esophagus.
High-speed reflectance confocal microscopy technology is capable of imaging individual eosinophils as highly scattering cells in the epithelium. The system has been successfully tested on patients and in semicommercial phase.
Optical coherence tomography is another medical imaging technique that has been implemented into tethered capsules Figure 7 E. This method implements low-coherence interferometry, in infrared wavelengths. Tethered quasi-digestible capsules based on optical coherence tomography are now used for esophagus disorders and checking the mucosa integrity in patients.
However, similar to the case of confocal microscopy systems, electronic and optical devices of these quasi-capsules are outside the body. So it is debatable how accurately such capsules can be considered as real ingestible devices. Incorporation of electrochemical sensors in ingestible capsule devices has been shown Figure 7 D. The capsule was tested in vitro on stool liquid, and consistency in measurement was shown.
The developers also demonstrated both cyclic and pulsed voltammetry. The challenge with chemical sensors is assuring their integrity for continuous measurements in the caustic area of the gut. Another possibility of transducer integration with ingestible capsule devices has been recently shown for ultrasound imaging. They incorporated four single element piezoelectric transducers in the capsule with an operation frequency of 15—50 MHz.
Ex vivo investigation on tissues have been conducted in the lab using this capsule, but it is not clear how the quality of images has been benchmarked. The capsule also interestingly contains white light fluorescence imaging with single photon avalanche detectors. Conclusions and Future Perspectives.
This paper provided an overview regarding the current state and prospective pathways of ingestible sensing capsule technology refer to Table 2 for a summary. The gut structure and functionalities were discussed to give the readers an understanding about the sensing and monitoring targets within the gut. New advances were discussed to show the rapid progress of this field in recent years.
Table 2. Therefore, it does not show a real world scenario where food and medical supplements are present. It is still limited to recognizing images and often difficult to assess the location of the capsule in the gut segment. Medtronic Given Imaging , CapsoVision, Olympus, Chongqing Jinshan Science and Technology, MiroCamRo capsule South Korea pH measuring acidity in different segments of the gut commercial: capable of gut localization, can provide information about diseases which are related to gut motility or the acidity of the gut The signal is noisy, still costly for the small amount of information it provides.
Medtronic Given Imaging , Olympus temperature measuring the core body temperature commercial: often used by soldiers in the field and also for sporting professionals, where accurate and remote measurement of body temperature is needed Low cost temperature capsule cannot provide gut localization information. Medtronic Given Imaging localization and monitoring monitoring the arrival of the capsule in different sections commercial: small size and can be efficiently used in monitoring adherence to therapeutic treatments It is always used with other pills.
Proteus Digital Health gas measuring different types of gases in the gut human trials: use gases as the byproduct of the gut activities to reveal food effect and diagnose gut disorders; signal to noise ratio is low for resistive based gas sensors; semiconducting, optical and thermal conductivity sensors have quasi linear responses and such high signal-to-noise ratio Definition of gas profiles should be identified.
Libraries for gas profiles of each gut disorders or food effect need to be established. Sensors should operate in both aerobic and anaerobic segments. Semiconducting and thermal conductivity sensors face selectivity challenges. Electrochemical gas sensors can be naturally noisy with unstable baselines. They can be noisy due to the nature of the electrochemical transducers. Stability remains an issue for these sensors as they are logarithmic due to the Nernst equation.
Therefore, the systems are quasi capsules with fiber optic connection. It is a quasi-capsule as it is tethered. Still the quality of the data should be improved and physician should become familiar with the meaning of the output data. It requires expert users which is costly. Still in early tests with advanced processing algorithms needed to understand the meaning of the obtained images.
The usage will require expert training and will be expensive. They are still expensive. NA raman spectroscopy creating raman spectra to sense the presence of chemical with vibrational raman signatures only concept based according to ref 96 : can potentially differentiate between many chemicals with high sensitivity The report is only a nonproven claim. Requires sophisticated and often bulky, accurate optical equipment for low detection sensing limits. NA physisorption sensors can be surface treated for sensing a variety of chemicals not tested yet: they have been successfully used for assessing organic vapors from fecal samples for diagnostics The selectivity can be a problem and they will need complex mathematical algorithms to extract the data.
NA surface acoustic wave measuring concentrations based on piezoelectric transducers not tested yet: they can sense materials of interest based on mass sensing at very low detection limits The vibration noise should be considered.
Signal-to-noise ratio can be a problem in actual measurements in the gut. There is no doubt that the amount of information obtainable from various ingestible sensor capsules passing along the gut is potentially tremendous. As human beings, we still have nearly no knowledge about many of the functionalities of the gut.
There are many unknowns about what occurs in the small intestine and colonic regions and their association with overall health. The importance of the microbiome and how it affects each organ of the body are increasingly being recognized. However, due to the diversity of the microbial families, their impacts in many areas are still unknown.
The knowledge about what digestive enzymes are capable of doing is limited to their basic functionalities. The operation of gut metabolites and hormones is not fully understood in each and every organ. Knowledge of electrolytes of the gut and how they change in response to food, medical supplements, and the environment is vague. Ingestible sensors for each and every aspect of the chemical changes of the gut should be developed to gain the needed knowledge and explore the functionality.
Based on large measurements, and against specific references, comprehensive libraries for healthy cohorts should be established. Such libraries will establish the base for comparison and benchmarking when the ingestible sensors are used for screening, diagnostics, and monitoring.
The field of ingestible sensors is still in its absolute infancy. Our information about many different sections of the gastrointestinal tract is still rudimentary, and many discoveries are waiting to be made. Our acquisition of knowledge of the gut is so far limited to just a few ingestible sensors including pH, temperature, and pressure capsules as well as camera based devices.
Even such capsules have only been used in relatively low numbers, considering the potential population in need of them. The costs associated with the use and administration of ingestible devices are still high, they have reliability issues, governmental regulatory barriers are still problematic, and lack of familiarity of medical doctors and food scientists with the output information from capsule signals is also a significant issue.
Ingestible sensing capsules have the capability to impact areas beyond their clinical applications for the prevention, diagnosis, and monitoring of gut disorders and gut related medical supplements. Smart pills can also provide invaluable information regarding food supplement influence on the individual including the effect of prebiotics and probiotics. This will revolutionize our understanding about food and how food affects our body, and also open the door to new market opportunities that are far larger than clinical diagnostics and monitoring markets.
Despite the early predictions that the field of ingestible sensors would experience a revolution after the emergence of the camera capsules in early s, progress in the field has been surprisingly slow. The field has seen some serious movement after , but as yet not many of the ideas have materialized commercially. The unnecessary barriers by the United States Food and Drug Administration FDA that classify ingestible capsules as class II medical devices have been a significant obstacle, imposing costly processes for obtaining approval for usage.
It is envisaged that advanced ingestible sensing capsules can go beyond standard diagnostic techniques by offering sampling, biopsy, tissue penetration, drug release, and specific actuations on demand. Ultimately, a new paradigm of doctor—patient care can be implemented with remote monitoring and administration. The possibilities are seemingly endless if the regulatory bodies can alter the traditional thinking on diagnostic technologies.
Author Information. Kyle J. D: Appl. Institute of Physics Publishing. Stretchable electronics, i. The potential applications range from fully conformable, stretchable, skin sensors for robotic devices, wearable electronic devices, to flesh-like biodevices. One of the challenges in the development of stretchable electronics is to retain full functionality under high external strains in stretching. In this paper, we review a few approaches recently developed for stretchable electronics and highlight recent research efforts on multi-directional writing for stretchable, three-dimensional structures.
A review. For at least the past ten years printed electronics has promised to revolutionize the authors' daily life by making cost-effective electronic circuits and sensors available through mass prodn. While passive components, such as conductors, resistors and capacitors, had already been fabricated by printing techniques at industrial scale, printing processes were struggling to meet the requirements for mass-produced electronics and optoelectronics applications despite their great potential.
In the case of logic integrated circuits ICs , which constitute the focus of this Progress Report, the main limitations were represented by the need of suitable functional inks, mainly high-mobility printable semiconductors and low sintering temp. These values were achieved thanks to the design and synthesis of donor-acceptor copolymers, showing limited degree of order when processed in thin films and therefore fostering further studies on the reason leading to such improved charge transport properties.
Among this class of materials, various polymers can show well balanced electrons and holes mobility, therefore being indicated as ambipolar semiconductors, good environmental stability, and a small band-gap, which simplifies the tuning of charge injection. This opened up the possibility of taking advantage of the superior performances offered by complementary CMOS-like logic for the design of digital ICs, easing the scaling down of crit.
Here, the authors review the recent progress in the development of printed ICs based on polymeric semiconductors suitable for large-vol. Particular attention is paid to the strategies proposed in the literature to design and synthesize high mobility polymers and to develop suitable printing tools and techniques to allow for improved patterning capability required for the down-scaling of devices to achieve the operation frequencies needed for applications, such as flexible radiofrequency identification RFID tags, near-field communication NFC devices, ambient electronics, and portable flexible displays.
Fiber-based structures are highly desirable for wearable electronics that are expected to be light-wt. Many fibrous structures were manufd. The advancement of nanotechnol. However, imparting electronic functions to porous, highly deformable and 3-dimensional fiber assemblies and maintaining them during wear represent great challenges from both views of fundamental understanding and practical implementation.
This article attempts to critically review the current state-of-arts with respect to materials, fabrication techniques, and structural design of devices as well as applications of the fiber-based wearable electronic products. This review elaborates the performance requirements of the fiber-based wearable electronic products, esp. Finally, discussions will be presented regarding to limitations of current materials, fabrication techniques, devices concerning manufacturability and performance as well as scientific understanding that must be improved prior to their wide adoption.
American Chemical Society. Wearable sensors have received considerable interest over the past decade owing to their tremendous promise for monitoring the wearers' health, fitness, and their surroundings. However, only limited attention has been directed at developing wearable chem. The development of wearable chem. This perspective reviews key challenges and technol. Size, rigidity, and operational requirements of present chem.
Sensor stability and on-body sensor surface regeneration constitute key anal. Similarly, present wearable power sources are incapable of meeting the requirements for wearable electronics owing to their low energy densities and slow recharging. Several energy-harvesting methodologies have inherent issues, including inconsistent power supply and limited stability. There are also major challenges pertaining to handling and securing the big data generated by wearable sensors.
These include achieving high data transfer rates and efficient data mining. Efforts must also be made toward developing next generation cryptol. The challenges facing the field of wearable chem. The article discusses these challenges and their potential solns. There is a growing demand for flexible and soft electronic devices. In particular, stretchable, skin-mountable, and wearable strain sensors are needed for several potential applications including personalized health-monitoring, human motion detection, human-machine interfaces, soft robotics, and so forth.
This Feature Article presents recent advancements in the development of flexible and stretchable strain sensors. The article shows that highly stretchable strain sensors are successfully being developed by new mechanisms such as disconnection between overlapped nanomaterials, crack propagation in thin films, and tunneling effect, different from traditional strain sensing mechanisms.
Strain sensing performances of recently reported strain sensors are comprehensively studied and discussed, showing that appropriate choice of composite structures as well as suitable interaction between functional nanomaterials and polymers are essential for the high performance strain sensing.
Next, simulation results of piezoresistivity of stretchable strain sensors by computational models are reported. Finally, potential applications of flexible strain sensors are described. This survey reveals that flexible, skin-mountable, and wearable strain sensors have potential in diverse applications while several grand challenges have to be still overcome.
This article reviews recent advances and developments in the field of wearable sensors with emphasis on a subclass of these devices that are able to perform highly-sensitive electrochem. Recent insights into novel fabrication methodologies and electrochem. Wearable electrochem. In this manner, multi-analyte detection can easily be performed, in real time, in order to ascertain the overall physiol.
Of profound importance is the development of an understanding of the impact of mech. We conclude this review with a retrospective outlook of the field and identify potential implications of this new sensing paradigm in the healthcare, fitness, security, and environmental monitoring domains. With continued innovation and detailed attention to core challenges, it is expected that wearable electrochem.
Elsevier Ltd. Wearable sensors have garnered considerable recent interest owing to their tremendous promise for a plethora of applications. Yet the absence of reliable non-invasive chem. A wide range of wearable electrochem. With continued innovation and attention to key challenges, such non-invasive electrochem. Elsevier B. The state of the art and future challenges related to wearable chem. Our attention is focused on the monitoring of biol. The development of such sensing devices is influenced by many factors and is usually addressed through the use of "smart materials" such as graphene, carbon nanotubes, poly ionic liqs.
These are seen as the pivotal steps towards the integration of chem. Jia, Wenzhao; Bandodkar, Amay J. The present work describes the first example of real-time noninvasive lactate sensing in human perspiration during exercise events using a flexible printed temporary-transfer tattoo electrochem. The new skin-worn enzymic biosensor exhibits chem. The device was applied successfully to human subjects for real-time continuous monitoring of sweat lactate dynamics during prolonged cycling exercise.
The resulting temporal lactate profiles reflect changes in the prodn. Such skin-worn metabolite biosensors could lead to useful insights into phys. Bandodkar, Amay J. This article describes the fabrication, characterization and application of an epidermal temporary-transfer tattoo-based potentiometric sensor, coupled with a miniaturized wearable wireless transceiver, for real-time monitoring of sodium in the human perspiration.
Sodium excreted during perspiration is an excellent marker for electrolyte imbalance and provides valuable information regarding an individual's phys. The realization of the new skin-worn non-invasive tattoo-like sensing device has been realized by amalgamating several state-of-the-art thick film, laser printing, solid-state potentiometry, fluidics and wireless technologies. The resulting tattoo-based potentiometric sodium sensor displays a rapid near-Nernstian response with negligible carryover effects, and good resiliency against various mech.
On-body testing of the tattoo sensor coupled to a wireless transceiver during exercise activity demonstrated its ability to continuously monitor sweat sodium dynamics. The real-time sweat sodium concn. The favorable anal. Guinovart, Tomas; Bandodkar, Amay J. Royal Society of Chemistry.
The development and anal. The fabrication of this skin-worn sensor, which is based on a screen-printed design, incorporates all-solid-state potentiometric sensor technol. The resulting tattooed potentiometric sensor exhibits a working range between M to 0. Testing under stringent mech. Since the levels of ammonium are related to the breakdown of proteins, the new wearable potentiometric tattoo sensor offers considerable promise for monitoring sport performance or detecting metabolic disorders in healthcare.
Such combination of the epidermal integration, screen-printed technol. Wearable digital health devices are dominantly found in rigid form factors such as bracelets and pucks. An adhesive radio-frequency identification RFID sensor bandage patch is reported, which can be made completely intimate with human skin, a distinct advantage for chronological monitoring of biomarkers in sweat. Optional paper microfluidics wick sweat from a sweat porous adhesive allowing flow to the sensor, or the sensor can be directly contacted to the skin.
The wearability of the patch has been demonstrated for up to seven days, and includes a protective textile which provides a feel and appearance similar to a standard Band-Aid. The design and fabrication of the patch are provided in full detail, as the basic components could be useful in the design of other wearable sensors. Nature Publishing Group. Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health.
Sampling human sweat, which is rich in physiol. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate anal.
Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is crit. Here we present a mech. Our work bridges the technol. This application could not have been realized using either of these technologies alone owing to their resp. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor phys.
This platform enables a wide range of personalized diagnostic and physiol. Homeostasis of ionized calcium in biofluids is crit. Measurement of ionized calcium for clin. Here, the authors demonstrate a wearable electrochem. This platform enables real-time quant. The authors' results show that the wearable sensors have high repeatability and selectivity to the target ions. Real-time on-body assessment of sweat is also performed, and the authors' results indicate that calcium concn.
This platform can be used in noninvasive continuous anal. Gao, Wei; Nyein, Hnin Y. A flexible and wearable microsensor array is described for simultaneous multiplexed monitoring of heavy metals in human body fluids. Zn, Cd, Pb, Cu, and Hg ions are chosen as target analytes for detection via electrochem. The oxidn. High selectivity, repeatability, and flexibility of the sensor arrays are presented.
Human sweat and urine samples are collected for heavy metal anal. Real-time on-body evaluation of heavy metal e. This platform is anticipated to provide insightful information about an individual's health state such as heavy metal exposure and aid the related clin. Recently microneedles have been explored for transdermal monitoring of biomarkers with the goal to achieve time-sensitive clin. In this highlight we provide a general overview of recent progress in microneedle-based sensing research, including: a glucose monitoring, b ex vitro microneedle diagnostic systems for general health monitoring with an emphasis on sensor construction, and c in vivo use of microneedle sensors.
The BION Bionic Neuron is a single channel implantable neurostimulator of unique design that can be delivered by injection. The development of the BION injectable neurostimulators exemplifies a challenging, but well posed medical design problem addressed with a successful strategy for prioritizing and resolving the biomedical and technological challenges. Though some performance requirements required post-evaluation revision, all fundamental goals were realized.
A small number of significant design corrections occurred because the device requirements did not include the full scope of environmental demands. The design has spawned a number of variants optimized for diverse biomedical applications, and its clinical applications continue to evolve. The BION development history demonstrates design successes worth emulating and design pitfalls that may be avoidable for future medical device development teams.
This paper serves as an introduction to the BION microstimulator technology and as an analysis of the design process used to develop the early clinical devices. We present the results from a retrospective review of data from patients with groin pain of various etiologies treated using neuromodulation of the dorsal root ganglion DRG.
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