Ingestible Capsule Research Articles

Validity of the estimated core temperature algorithm during real-world prolonged walking exercise under warm ambient conditions

BackgroundNon-invasive methods to estimate core body temperature (TC) are increasingly available. We examined the group-level and individual participant-level validity of the Estimated Core Temperature (ECTemp™) algorithm to estimate TC based on sequential heart rate (HR) measurements during real-world prolonged walking exercise in warm ambient conditions. MethodsParticipants walked 30 (n = 3), 40 (n = 13) or 50 (n = 2) km on a self-selected pace during which TC was measured every minute using an ingestible temperature capsule. HR was measured every second and used to compute the estimated core temperature (TC-est) using the ECTemp™ algorithm. Bland-Altman analyses were performed to assess agreement between TC and TC-est. A systematic bias <0.1 °C was considered acceptable. Results18 participants (56 ± 16 years, 11 males) walked for 549 min (range 418–645 min), while ambient temperature increased from 22 °C to 29 °C. Average HR was 108 ± 13 bpm and TC ranged from 36.9 to 39.2 °C, whereas TC-est ranged from 36.8 to 38.9 °C (n = 8572 observations). Group level data revealed a systematic bias of 0.09 °C (p < 0.001) with limits of agreements of ±0.44 °C. A weak correlation was found between TC and TC-est (r = 0.28; p < 0.001). Large inter-individual differences in bias (range −0.45 °C to 0.62 °C) and correlation coefficients (range −0.09 to 0.95) were found, while only 3 participants (17%) had an acceptable systemic bias of <0.1 °C. ConclusionGroup level data showed that the ECTemp™ algorithm had an acceptable systematic bias during prolonged walking exercise in warm ambient conditions, but only 3 out of 18 participants had an acceptable systemic bias. Future studies are needed to improve the accuracy of the algorithm before individual users can rely on their estimated TC during real-world exercise.

Optimized Magnetically Docked Ingestible Capsules for Non‐Invasive Refilling of Implantable Devices

Automated drug delivery systems (ADDS) improve chronic disease management by enhancing adherence and reducing patient burden, particularly in conditions like type 1 diabetes, through intraperitoneal insulin delivery. However, periodic invasive refilling of the reservoir is needed in such a class of implantable devices. In previous work, an implantable ADDS with a capsule docking system is introduced for non‐invasive reservoir refilling. Yet, it encounters reliability issues in manufacturing, sealing, and docking design and lacks evidence on intestinal tissue compression effects and chronic in vivo data. This work proposes an optimization of the different components featuring this ADDS. The ingestible capsule is designed, developed, and tested following ISO 13485, exhibiting high insulin stability and optimal sealing for six days in harsh gastrointestinal‐like conditions. A magnetic docking system is optimized, ensuring reliable and stable capsule docking at a clinically relevant distance of 5.92 mm. Histological tests on human intestinal tissues confirm safe capsule compression during docking. Bench tests demonstrate that the integrated mechatronic system effectively docks capsules at various peristalsis‐mimicking velocities. A six‐week in vivo test on porcine models demonstrates chronic safety and provides hints on fibrotic reactions. These results pave the way for the further evolution of implantable ADDS.

Magnetically triggered ingestible capsule for localized microneedle drug delivery

Magnetically triggered ingestible capsule for localized microneedle drug delivery

A circadian-informed lighting intervention accelerates circadian adjustment to a night work schedule in a submarine lighting environment.

Night work has detrimental impacts on sleep and performance, primarily due to misalignment between sleep-wake schedules and underlying circadian rhythms. This study tested whether circadian-informed lighting accelerated circadian phase delay, and thus adjustment to night work, compared to blue-depleted standard lighting under simulated submariner work conditions. Nineteen healthy sleepers (12 males; mean±SD aged 29 ±10 y) participated in two separate 8-day visits approximately one month apart to receive, in random order, circadian-informed lighting (blue-enriched and dim, blue-depleted lighting at specific times) and standard lighting (dim, blue-depleted lighting). After an adaptation night (day 1), salivary dim light melatonin onset (DLMO) assessment was undertaken from 18:00-02:00 on days 2-3. During days 3-7, participants completed simulated night work from 00:00-08:00 and a sleep period from 10:00-19:00. Post-condition DLMO assessment occurred from 21:00-13:00 on days 7-8. Ingestible capsules continuously sampled temperature to estimate daily core body temperature minimum (Tmin) time. Tmin and DLMO circadian delays were compared between conditions using mixed effects models. There were significant condition-by-day interactions in Tmin and DLMO delays (both p<0.001). After four simulated night shifts, circadian-informed lighting produced a mean [95%CI] 4.3 [3.3 to 5.4] h greater delay in Tmin timing and a 4.2 [3 to 5.6] h greater delay in DLMO timing compared to standard lighting. Circadian-informed lighting accelerates adjustment to shiftwork in a simulated submariner work environment. Circadian lighting interventions warrant consideration in any dimly lit and blue-depleted work environments where circadian adjustment is relevant to help enhance human performance, safety, and health.

A non-invasive tool to collect small intestine content in post weaning pigs: validation study.

The Capsule for Sampling (CapSa) is an ingestible capsule that collects small intestine content while transiting through the natural digestive pathway. In this study, 14 Swiss Large White pigs weighing less than 12kg (Category < 12kg) and 12 weighing between 12 and 20kg (Category [12-20kg]) were given two CapSas and monitored for three days. The animals were euthanized for post-mortem sampling, allowing us to directly obtain gut microbiota samples from the gastrointestinal tract. This post-mortem approach enabled a direct comparison between the microbial content from the gut and the samples collected via the CapSas, and it also facilitated precise identification of the CapSas' sampling sites within the gastrointestinal tract. For the category under 12kg, only 2.3% of the administered CapSas were recovered from the feces. In contrast, in the 12-20kg category, 62.5% of the CapSas were successfully retrieved from the feces within 48h. Of these recovered CapSas, 73.3%-equating to 11 capsules from eight pigs-had a pH > 5.5 and were therefore selected for microbiome analysis. Bacterial composition of the CapSas was compared with that of the three segments of the small intestine, the large intestine and feces of the corresponding pig. The results were tested using a PERMANOVA model (Adonis) including sample type as a factor, and then pairwise comparisons were made. The bacterial composition found in the CapSas differed from that of the large intestine and feces (P < 0.01), while it did not differ from the first segment of the small intestine (P > 0.10). This study provides evidence that the CapSa effectively samples the intestinal microbiota from the upper section of the small intestine in post-weaning pigs. Furthermore, it was found that the collection of CapSas could only be successfully achieved in pigs classified within the heavier weight category.

An ingestible near-infrared fluorescence capsule endoscopy for specific gastrointestinal diagnoses

Early diagnosis of gastrointestinal (GI) diseases is important to effectively prevent carcinogenesis. Capsule endoscopy (CE) can address the pain caused by wired endoscopy in GI diagnosis. However, existing CE approaches have difficulty effectively diagnosing lesions that do not exhibit obvious morphological changes. In addition, the current CE cannot achieve wireless energy supply and attitude control at the same time. Here, we successfully developed a novel near-infrared fluorescence capsule endoscopy (NIFCE) that can stimulate and capture near-infrared (NIR) fluorescence images to specifically identify subtle mucosal microlesions and submucosal lesions while capturing conventional white light (WL) images to detect lesions with significant morphological changes. Furthermore, we constructed the first synergetic system that simultaneously enables multi-attitude control in NIFCE and supplies long-term power, thus addressing the issue of excessive power consumption caused by the NIFCE emitting near-infrared light (NIRL). We performed in vivo experiments to verify that the NIFCE can specifically "light up" tumors while sparing normal tissues by synergizing with probes actively aggregated in tumors, thus realizing specific detection and penetration. The prototype NIFCE system represents a significant step forward in the field of CE and shows great potential in efficiently achieving early targeted diagnosis of various GI diseases.

Electronic‐Free Traceable Smart Capsule for Gastrointestinal Microbiome Sampling

AbstractNon‐invasive smart electronic‐free sampling capsules have revolutionized the exploration of microbiome‐disease interactions in inaccessible regions of the gastrointestinal (GI) tract. However, a significant impediment to the broader use of electronic‐free capsules is the challenge of reliably tracking and determining their in vivo location. Variability in patient motility introduces uncertainties in capsule position. Thus, there is a critical need for effective solutions that ensure traceability in microbiome studies employing such capsules. While tracking methods are explored in previous smart ingestible capsule designs, most have relied on RF, imaging, and radiation‐based techniques, limiting sampling volume, increasing costs, complicating design, and raising health concerns due to ionizing radiation exposure. To address these challenges, the design of an electronic‐free smart capsule is introduced that integrates a metal tracer for easy metal detection, serving as a reliable tracking mechanism. The capsule is housed in a 3D‐printed casing and includes a superabsorbent hydrogel serving as both a sampling medium and an actuator within the capsule. The capsule's targeted sampling of the GI tract is accomplished by covering the capsule's sampling port with a pH‐responsive coating. Optimal dimensions and material for the cylindrical shaped metal tracer on the capsule are determined through extensive optimizations, considering factors such as gastric flotation, corrosion resistance, read distance, and omnidirectional detectability. The results of these investigations reveal that a 12 mm stainless steel (SS 316L) cylinder offers the necessary detection and tracing capabilities with minimal toxicity and excellent corrosion resistance under relevant physiological conditions in the GI tract. Validation studies, both in vitro and in vivo, confirmed the capsule's trackability using a handheld metal detector. These findings are further validated by X‐ray imaging and CT scans, demonstrating the metal detector's ability to distinguish approximate GI tract regions and determine the time point of excretion. This innovative approach provides a reliable and cost‐effective solution for tracking electronic‐free smart capsules, enhancing their applicability in microbiome research for both human and animal studies.

Assessment of the Smartpill, a Wireless Sensor, as a Measurement Tool for Intra-Abdominal Pressure (IAP).

Background: The SmartPill, a multisensor ingestible capsule, is marketed for intestinal motility disorders. It includes a pressure sensor, which could be used to study intra-abdominal pressure (IAP) variations. However, the validation data are lacking for this use. Material and Methods: An experimental study was conducted on anesthetized pigs with stepwise variations of IAP (from 0 to 15 mmHg by 3 mmHg steps) generated by laparoscopic insufflation. A SmartPill, inserted by endoscopy, provided intragastric pressure data. These data were compensated to take into account the intrabdominal temperature. They were compared to the pressure recorded by intragastric (IG) and intraperitoneal (IP) wired sensors by statistical Spearman and Bland-Altmann analysis. Results: More than 4500 pressure values for each sensor were generated on two animals. The IG pressure values obtained with the SmartPill were correlated with the IG pressure values obtained with the wired sensor (respectively, Spearman ρ coefficients 0.90 ± 0.08 and 0.72 ± 0.25; bias of -28 ± -0.3 mmHg and -29.2 ± 0.5 mmHg for pigs 1 and 2). The intragastric SmartPill values were also correlated with the IAP measured intra-peritoneally (respectively, Spearman ρ coefficients 0.49 ± 0.18 and 0.57 ± 0.30; bias of -29 ± 1 mmHg and -31 ± 0.7 mmHg for pigs 1 and 2). Conclusions: The SmartPill is a wireless and painless sensor that appears to correctly monitor IAP variations.

Feasibility analysis of applying non-invasive core body temperature measurement in sleep research

Core body temperature (CBT) emerges as a pivotal physiological marker in sleep research, and the commonly employed invasive CBT measurements significantly disrupt the sleep process itself. Non-invasive CBT measurement offers a viable solution to this challenge but lack validation. In this sleep study, simultaneous invasive and non-invasive measurements of CBT were conducted on 14 subjects. Ingestible capsule was chosen to represent invasive measurement, while external GreenTeg patch was selected as representative device for non-invasive measurement. Quantitative comparisons of two measurements were conducted from four perspectives: correlation, consistency, difference, and stability, and results indicated: (1) A significant correlation was observed between two real-time measurements, and correlation became stronger as ambient temperature decreased. (2) Consistency of most data group can be acceptable as most of them fell within the 95% agreement range. (3) Non-invasive instrument exhibited substantial error for unstable core temperature, yet displayed relatively small error for stable core temperature. (4) Stability of difference between two measurements was poor during 64.3% of the time intervals, and this performance deteriorated further in unstable state. In summary, existing non-invasive measurement can serve as a reference for sleep research, but caution is warranted when applying it to real-time and unstable analyses. Additionally, feasibility of algorithm optimization makes the future of non-invasive measurements promising.

Miniaturized Capsule System Toward Real-Time Electrochemical Detection of H2 S in the Gastrointestinal Tract.

Hydrogen sulfide (H2 S) is a gaseous inflammatory mediator and important signaling molecule for maintaining gastrointestinal (GI) homeostasis. Excess intraluminal H2 S in the GI tract has been implicated in inflammatory bowel disease and neurodegenerative disorders; however, the role of H2 S in disease pathogenesis and progression is unclear. Herein, an electrochemical gas-sensing ingestible capsule is developed to enable real-time, wireless amperometric measurement of H2 S in GI conditions. A gold (Au) three-electrode sensor is modified with a Nafion solid-polymer electrolyte (Nafion-Au) to enhance selectivity toward H2 S in humid environments. The Nafion-Au sensor-integrated capsule shows a linear current response in H2 S concentration ranging from 0.21 to 4.5ppm (R2 = 0.954) with a normalized sensitivity of 12.4% ppm-1 when evaluated in a benchtop setting. The sensor proves highly selective toward H2 S in the presence of known interferent gases, such as hydrogen (H2 ), with a selectivity ratio of H2 S:H2 = 1340, as well as toward methane (CH4 ) and carbon dioxide (CO2 ). The packaged capsule demonstrates reliable wireless communication through abdominal tissue analogues, comparable to GI dielectric properties. Also, an assessment of sensor drift and threshold-based notification is investigated, showing potential for in vivo application. Thus, the developed H2 S capsule platform provides an analytical tool to uncover the complex biology-modulating effects of intraluminal H2 S.

O003 Investigating the relationship between core body temperature and changes in cognitive performance during simulated night shifts

Abstract Introduction The timing of circadian and sleep-wake behaviours is disrupted by night shift-work. Interventions involving light may prove beneficial in adjusting the circadian rhythm to shift work, although the changes in vigilance remain uncertain. This study examined the temporal relationship between core body temperature (CBT) rhythm and vigilance during a work-shift through lighting. Methods 19 healthy individuals (12 males, mean±SD age of 28.7±10.4 years) participated in two 8-day experimental conditions with 4 days of circadian-informed lighting vs standard lighting. On Day 2, participants transitioned from a typical day-night wake-sleep schedule to night shift-work from 00:00 to 08:00 on Days 3 to 7. Psychomotor vigilance tasks (PVTs) were administered six times on shift. CBT was monitored via ingestible capsules. Daily CBT minimum (CBTmin) time was compared to the timing of the worst PVT performance on-shift (task with most lapses). Results In the parent study, circadian lighting improved on-shift performance and sleep quality. These effects were accompanied by a significant day-by-condition interaction effect on the degree of temporal offset between CBTmin time and worst PVT performance time during the work shift, F(3,74.660)= 4.09, p=0.01; the disparity increased over successive days under the influence of circadian-informed lighting compared to standard lighting., p&amp;lt;0.01. Conclusions The modest adjustment in the timing of the worst on-shift performance provides support that circadian lighting improves on-shift performance. These results emphasise the importance of considering the combined impact of circadian rhythms, sleep patterns, and time-on-task effects on performance outcomes when assessing fatigue and implementing countermeasures to phase-shift biological rhythms.

FRI415 Patient Preference And Proof-of-concept For A Once-daily Follicle Stimulating Hormone (FSH) Biosimilar Delivered Via An Orally Ingestible Robotic Pill (RT-112)

Abstract Disclosure: A. Yamaguchi: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. K. Horlen: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. N. Patel: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. V. Tran: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A.T. Vo: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. R. Medida: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. J.T. Myers: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. L.C. Fung: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. K. Kaminskaya: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. D. Mohan: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. V. Nguyen: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. S. Nguyen: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. B. Syed: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A.K. Dhalla: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. M. Imran: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. M.A. Hashim: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. Background: Biotherapeutics offer effective treatments for reproductive disorders, but require painful parenteral (e.g., subcutaneous (SC)) injections, representing a burden for patients which interferes with comfort and quality of life. We have developed an orally ingestible robotic pill (RP) that can deliver biotherapeutic agents with bioavailability rivalling or surpassing that of parenteral injections. Here, we provide 1) clinical evidence of patient preference for the daily oral RP over parenteral injection therapy and 2) data from a study of awake canines demonstrating comparable serum exposures of FSH via the oral RP versus SC injection. Methods:Patient Preference Study: A total of 150 participants currently using parenteral injections were enrolled and given a mock-RP having the same physical characteristics of a RP but without a needle or drug inside. After swallowing the mock-RP, participants were asked to complete a questionnaire evaluating their experience and their preference for a pill vs. parenteral injection. Nonclinical Proof-of-Concept: Single doses of RT-112 (150 IU (n=7) and 450 IU (n=8)) were orally administered to awake, fasted Beagle dogs (7.0-13.0 kg body weight); a control group (n=3) received a dose of 20 IU/kg (∼180 IU) FSH via SC injection. Serial blood samples were collected over 5 days and serum FSH concentrations were quantified via a qualified ELISA. Results: All participants (150/150) in the patient preference study were able to swallow the mock-RP without any adverse events. Based on the questionnaire, the overall preference for an oral pill over parenteral injection was 91%, irrespective of age (21-50, 51-65, 66-75 years). Oral administration of FSH at the 2 doses via RT-112 to awake canines elicited dose proportional increases in serum drug concentrations. AUC0-t values for the 150 IU and 450 IU dose groups were 2101 ± 185 and 8179 ± 733 mIU*hr/mL, and Cmax values were 65 ± 13 and 224 ± 24 mIU/mL, respectively. The pharmacokinetic (PK) profile of the lower RT-112 dose was similar to that of the SC Control dose (AUC0-t: 2131 ± 67 mIU*hr/mL, Cmax: 52 ± 1 mIU/mL), with a relative bioavailability nearly identical (99%) to that of the SC injection. Conclusions: Patients strongly prefer an oral therapeutic option over parenteral therapy. In awake canines, FSH delivered via oral RP yielded bioavailability very similar to SC injection. These data provide early proof-of-concept of the feasibility of replacing the current parenteral injections of FSH with orally ingestible capsules utilizing the RP. Presentation: Friday, June 16, 2023

Gastrointestinal Transit Times in Health as Determined Using Ingestible Capsule Systems: A Systematic Review.

Ingestible capsule (IC) systems can assess gastrointestinal (GI) transit times as a surrogate for gut motility for extended periods of time within a minimally invasive, radiation-free and ambulatory setting. A literature review of IC systems and a systematic review of studies utilizing IC systems to measure GI transit times in healthy volunteers was performed. Screening for eligible studies, data extraction and bias assessments was performed by two reviewers. A narrative synthesis of the results was performed. The literature review identified 23 different IC systems. The systematic review found 6892 records, of which 22 studies were eligible. GI transit time data were available from a total of 1885 healthy volunteers. Overall, seventeen included studies reported gastric emptying time (GET) and small intestinal transit time (SITT). Colonic transit time (CTT) was reported in nine studies and whole gut transit time (WGTT) was reported in eleven studies. GI transit times in the included studies ranged between 0.4 and 15.3 h for GET, 3.3-7 h for SITT, 15.9-28.9 h for CTT and 23.0-37.4 h for WGTT. GI transit times, notably GET, were influenced by the study protocol. This review provides an up-to-date overview of IC systems and reference ranges for GI transit times. It also highlights the need to standardise protocols to differentiate between normal and pathological function.

Freestanding region-responsive bilayer for functional packaging of ingestible devices

Ingestible capsules have the potential to become an attractive alternative to traditional means of treating and detecting gastrointestinal (GI) disease. As device complexity increases, so too does the demand for more effective capsule packaging technologies to elegantly target specific GI locations. While pH-responsive coatings have been traditionally used for the passive targeting of specific GI regions, their application is limited due to the geometric restrictions imposed by standard coating methods. Dip, pan, and spray coating methods only enable the protection of microscale unsupported openings against the harsh GI environment. However, some emerging technologies have millimeter-scale components for performing functions such as sensing and drug delivery. To this end, we present the freestanding region-responsive bilayer (FRRB), a packaging technology for ingestible capsules that can be readily applied for various functional ingestible capsule components. The bilayer is composed of rigid polyethylene glycol (PEG) under a flexible pH-responsive Eudragit® FL 30 D 55, which protects the contents of the capsule until it arrives in the targeted intestinal environment. The FRRB can be fabricated in a multitude of shapes that facilitate various functional packaging mechanisms, some of which are demonstrated here. In this paper, we characterize and validate the use of this technology in a simulated intestinal environment, confirming that the FRRB can be tuned for small intestinal release. We also show a case example where the FRRB is used to protect and expose a thermomechanical actuator for targeted drug delivery.

Magnetic Localization of Wireless Ingestible Capsules Using a Belt-Shaped Array Transmitter

In the last 20 years, research into and clinical use of wireless ingestible capsules (WIC) has increased, with capsule endoscopy being the most common application in clinical practice. Additionally, there has been an increased research interest in sensing capsules. To maximize the usefulness of the information provided by these devices, it is crucial to know their location within the gastrointestinal tract. The main WIC localization methods in research include radio frequency approaches, video-based methods, and magnetic-based methods. Of these methods, the magnetic-based methods show the most potential in terms of localization accuracy. However, the need for an external transmitting (or sensing) array poses an important limitation, as evidenced by most of the reported methods involving a rigid structure. This poses a challenge to its wearability and performance in daily life environments. This paper provides an overview of the state of the art on magnetic-based localization for WIC, followed by a proof of concept of a system that aims to solve the wearability challenges. Comparative performance simulations of different transmitter arrays are presented. The effect of including one or two receiver coils in the WIC is also evaluated in the simulation. Experimental localization results for a planar transmitter array and for a more wearable belt-shaped transmitter are presented and compared. A localization mean absolute error (MAE) as low as 6.5 mm was achieved for the planar array in a volume of 15 cm × 15 cm × 15 cm, starting at a 5 cm distance from the transmitter. Evaluating the belt array in a similar volume of interest (15 cm × 15 cm × 15 cm starting at 7.5 cm distance from the transmitter) resulted in an MAE of 13.1 mm across the volume and a plane-specific MAE as low as 9.5 mm when evaluated at a 12.5 cm distance. These initial results demonstrate comparable performances between these two transmitters, while the belt array has the potential to enable measurements in daily-life environments. Despite these promising results, it was identified that an improvement in the model for the magnetic field when using transmitter coils with ferrite cores is necessary and is likely to result in better localization accuracy. This belt-array approach, together with compensation techniques for body motion, as recently reported for rigid arrays, has the potential to enable WIC localization in uncontrolled environments with minimal impact on the user’s daily life.

Biosensors for point-of-care testing and personalized monitoring of gastrointestinal microbiota.

The gastrointestinal (GI) microbiota is essential in maintaining human health. Alteration of the GI microbiota or gut microbiota (GM) from homeostasis (i.e., dysbiosis) is associated with several communicable and non-communicable diseases. Thus, it is crucial to constantly monitor the GM composition and host-microbe interactions in the GI tract since they could provide vital health information and indicate possible predispositions to various diseases. Pathogens in the GI tract must be detected early to prevent dysbiosis and related diseases. Similarly, the consumed beneficial microbial strains (i.e., probiotics) also require real-time monitoring to quantify the actual number of their colony-forming units within the GI tract. Unfortunately, due to the inherent limitations associated with the conventional methods, routine monitoring of one's GM health is not attainable till date. In this context, miniaturized diagnostic devices such as biosensors could provide alternative and rapid detection methods by offering robust, affordable, portable, convenient, and reliable technology. Though biosensors for GM are still at a relatively preliminary stage, they can potentially transform clinical diagnosis in the near future. In this mini-review, we have discussed the significance and recent advancements of biosensors in monitoring GM. Finally, the progresses on future biosensing techniques such as lab-on-chip, smart materials, ingestible capsules, wearable devices, and fusion of machine learning/artificial intelligence (ML/AI) have also been highlighted.

0015 A circadian-informed lighting intervention markedly accelerates circadian adjustment to a night shift-work schedule

Abstract Introduction Night shift-work results in misalignment between circadian timing and the sleep/wake schedule, negatively impacting sleep and performance. In encapsulated environments (e.g., submarines), the lack of strong daily solar lighting cues may impair circadian entrainment to the night shift-work schedule. This study designed and tested a circadian-informed lighting strategy to promote faster circadian phase delays to adjust to night shift-work compared to standard lighting. Methods Nineteen healthy sleepers (12 males/7 females, mean±SD aged 28.7±10.4 years) underwent two separate 8-day experimental conditions (circadian-informed lighting versus standard lighting). After a baseline sleep from 22:00 – 07:00 (day 1) and salivary dim light melatonin onset assessment ([DLMO], day 2), participants undertook simulated night shift-work (00:00 - 08:00) and slept during the day (10:00 - 19:00) for days 3-7 followed by a post-DLMO assessment on day 8. Ingestible capsules collected core body temperature (CBT) continuously throughout days 2-8, and cosine curve fitting was applied to estimate the timing of each daily temperature minima. The standard lighting condition mimicked current lighting on submarines (largely dim, blue-depleted light), while the circadian-informed lighting administered bright, blue-enriched and dim, blue-depleted lighting at times estimated to facilitate rapid circadian delay. The magnitude of daily CBT minima changes and the delay in pre- vs. post-DLMO were compared across conditions. Results There were significant day-by-condition interactions on CBT minima timing and DLMO timing (both p&amp;lt; 0.001). After 4 days of simulated night-shift work there was a mean [95%CI] 4.5 [3.4 to 5.7] hour greater delay in CBT minima and a 4.6 [3.6 to 5.6] hour greater delay in DLMO timing compared to standard lighting, equating to 3.6 and 2.4-fold faster delays in DLMO and CBT minima timing shifts, respectively. Conclusion Circadian-informed lighting substantially accelerates circadian re-adjustment to night shift-work. Lighting interventions could usefully improve sleep, performance, and safety in shift-workers. Support (if any) This research is supported by the Commonwealth of Australia as represented by the Defence Science and Technology Group of the Department of Defence through the Research Network for Undersea Decision Superiority (research agreement number: 9334), with additional financial support from Flinders University and lighting provision support from REDARC.

Bioinspired, ingestible electroceutical capsules for hunger-regulating hormone modulation.

The gut-brain axis, which is mediated via enteric and central neurohormonal signaling, is known to regulate a broad set of physiological functions from feeding to emotional behavior. Various pharmaceuticals and surgical interventions, such as motility agents and bariatric surgery, are used to modulate this axis. Such approaches, however, are associated with off-target effects or post-procedure recovery time and expose patients to substantial risks. Electrical stimulation has also been used to attempt to modulate the gut-brain axis with greater spatial and temporal resolution. Electrical stimulation of the gastrointestinal (GI) tract, however, has generally required invasive intervention for electrode placement on serosal tissue. Stimulating mucosal tissue remains challenging because of the presence of gastric and intestinal fluid, which can influence the effectiveness of local luminal stimulation. Here, we report the development of a bioinspired ingestible fluid-wicking capsule for active stimulation and hormone modulation (FLASH) capable of rapidly wicking fluid and locally stimulating mucosal tissue, resulting in systemic modulation of an orexigenic GI hormone. Drawing inspiration from Moloch horridus, the "thorny devil" lizard with water-wicking skin, we developed a capsule surface capable of displacing fluid. We characterized the stimulation parameters for modulation of various GI hormones in a porcine model and applied these parameters to an ingestible capsule system. FLASH can be orally administered to modulate GI hormones and is safely excreted with no adverse effects in porcine models. We anticipate that this device could be used to treat metabolic, GI, and neuropsychiatric disorders noninvasively with minimal off-target effects.

Gelatin-Based Ingestible Impedance Sensor to Evaluate Gastrointestinal Epithelial Barriers.

Low-profile and transient ingestible electronic capsules for diagnostics and therapeutics can replace widely used yet invasive procedures such as endoscopies. Several gastrointestinal diseases such as reflux disease, Crohn's disease, irritable bowel syndrome, and eosinophilic esophagitis result in increased intercellular dilation in epithelial barriers. Currently, the primary method of diagnosing and monitoring epithelial barrier integrity is via endoscopic tissue biopsies followed by histological imaging. Here, a gelatin-based ingestible electronic capsule that can monitor epithelial barriers via electrochemical impedance measurements is proposed. Toward this end, material-specific transfer printing methodologies to manufacture soft-gelatin-based electronics, an in vitro synthetic disease model to validate impedance-based sensing, and tests of capsules using ex vivo using porcine esophageal tissue are described. The technologies described herein can advance next generation of oral diagnostic devices that reduce invasiveness and improve convenience for patients.

A Threshold-Based Bioluminescence Detector With a CMOS-Integrated Photodiode Array in 65 nm for a Multi-Diagnostic Ingestible Capsule

This article presents a highly miniaturized ingestible electronic capsule for biochemical detection via onboard genetically engineered biosensor bacteria. The core integrated circuit (IC) is a threshold-based bioluminescence detector with a CMOS-integrated photodiode array in a 65-nm technology that utilizes a dual-duty-cycling front end to achieve low power consumption. The implemented IC achieved 59-nW active power consumption, 25-fA/count resolution, and a 59-fA minimum detectable signal (MDS) using a calibrated optical source. The IC was then integrated with other system components into a battery-powered wireless ingestible capsule measuring just 6.5 mm thick <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\times $ </tex-math></inline-formula> 12 mm diameter. We demonstrated successful detection of low-intensity bioluminescent signals from bioengineered bacterial sensors when exposed to the intestinal inflammation biomarker tetrathionate in vitro. Together, the IC and mm-scale smart pill systems demonstrate high sensitivity with low-power multiplexed measurement capability suitable for noninvasive disease diagnosis and monitoring in the gastrointestinal (GI) tract.