RELATED APPLICATION DATA

[0001] The present application claims benefit of co-pending U.S. provisional application Serial No. 63/280,951, filed November 18, 2021, the entire disclosure of which is expressly incorporated by reference herein.

TECHNICAL FIELD

[0002] The present application relates generally to health monitoring devices, systems, and methods and, more particularly, to devices, systems, and methods for monitoring and/or analyzing a subject during defecation to identify viruses, e.g., to identify the presence of SARS-CoV-2 RNA or DNA, cancers, and/or other biomarkers.

BACKGROUND

[0003] The early detection and treatment of diseases can result in an improved prognosis and increased quality of life. To detect various diseases including cancer, diabetes, and renal disease early, it is desirable to establish a platform capable of routinely monitoring human health, e.g., to establish a patient-specific baseline for diagnostic biomarkers. Having established a baseline, detecting trends may allow physicians to warn users that they might be developing an illness. Unfortunately, patients have biomarkers measured irregularly, usually when they are already experiencing symptoms, which may hamper the ability of physicians to establish reliable baselines.

[0004] Invasive procedures such as surgery and X-ray imaging are not the best options for continuous monitoring since they are costly and can be burdensome for the general population. Sources of diagnostic information include the molecular contents of sweat, saliva, urine, and feces, all of which are naturally excreted every day and packed with information. Much research has indicated that these substances can provide clues to our health and can be continuously obtained through the development of appropriate diagnostic tools.

[0005] Therefore, systems and methods for monitoring a subject’s health would be useful. SUMMARY

[0006] The present application is directed to health monitoring devices, systems, and methods, and, more particularly, to systems and methods for monitoring and/or analyzing a subject during defecation. More particularly, the present application is directed to devices and systems that may be added to a toilet or integral toilet systems that monitor and/or analyze the subject’s excreta, e.g., stools during defecation, to, e.g., identify the presence of viruses, such as SARS-CoV-2 RNA and/or DNA, cancers, and/or other target biomarkers, such as proteins, and to methods for using such devices and systems.

[0007] The immediate containment of coronavirus disease 2019 (CO VID-19) will rely on broad testing and early detection and isolation of infected patients. However, our current testing capabilities are limited, and densely populated essential communities, such as those in a military setting, are particularly vulnerable due to being unable to socially distance. Gastrointestinal (GI) symptoms can often precede respiratory symptoms in COVID-19 infection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA) can be found in the stool of both symptomatic and asymptomatic patients; this presents an opportunity for surveillance of COVID-19 by non-invasive and longitudinal monitoring of fecal viral RNA.

[0008] Several studies have described the potential GI tropism of SARS-CoV-2. In one report, 49% of CO VID-19 positive patients experienced GI symptoms such as diarrhea or abdominal discomfort prior to the onset of respiratory symptoms, while another study noted detectable viral fecal RNA in 29% of study subjects. SARS-CoV-2 RNA can be found in the feces even after respiratory symptoms resolve and nearly five weeks after nasopharyngeal tests become negative, implying the importance of longitudinal fecal testing. Additionally, even patients with asymptomatic COVID-19 infections (35%) are still capable of transmitting the virus, further emphasizing the need for repeated testing to accurately detect infection and monitor recovery. The standard COVID-19 test is a nasopharyngeal swab which requires close human interaction (within an arm’s length) and is uncomfortable, usually triggering a cough or sneeze that increases the risk of exposure to the testers.

[0009] The present application relates to devices and methods that allow routine fecal viral RNA testing with a COV-ID (Coronavirus Identification) toilet that may expand CO VID-19 testing capabilities, enable early detection of outbreaks and potential superspreaders, and limit the spread of infection within highly organized essential communities. [00010] In one example, a toilet-mounted automated stool testing system is provided that may include auto-sanitizing features for COVID-19 detection, which may be installed on existing toilets, e.g., in military barracks and ship berths, to provide a hygienic, low- barrier testing location for service members and/or others. Military personnel are essential workers who provide national security as well as aid in controlling the COVID-19 pandemic via components such as the National Guard and naval hospital ships but face difficulties in maintaining social distancing. Active-duty personnel are often required to be in shared barracks or 96-person ship berths sleeping inches away from each other, and are thus especially vulnerable to the spread of COVID-19. The COV-ID toilet described herein has the capacity to perform automated hands-free testing, self-sanitization to minimize fecal- oral transmission, and facilitate longitudinal testing to identify infected and potentially asymptomatic individuals before the manifestation of COVID-19 resulting in minimizing transmission within these essential populations.

[00011] The devices herein may be mounted on or integrated into a toilet, and automatically monitor and/or inspect a subject’s excreta, e.g., to inspect for the presence of SARS-CoV-2 RNA and/or other markers in the excreta voided by the users of the devices. The devices may be configured not to interfere with normal human behavior using the toilet and, optionally, may include one or more of automatic user identification, excretion detection, and/or analysis features, as described elsewhere herein and in U.S. application Serial No. 16/506,942, the entire disclosure of which is incorporated by reference herein. [00012] In accordance with one example, a device is provided for analyzing excreta of a subject using a toilet that includes a housing mountable on a toilet adjacent the toilet bowl; a stool collection module for collecting stool samples from a subject using the toilet; an extraction module for extracting one or more biomarkers from the collected stool samples; a testing module for testing the one or more biomarkers to identify the presence of target RNA, DNA, proteins, and/or other biomarkers, e.g., viruses, such as SARS-CoV-2, cancers, and the like; and a sanitization module for sanitizing the toilet between users.

[00013] In accordance with another example, a device is provided for analyzing excreta of a subject that includes a toilet comprising a toilet bowl and a toilet seat mounted to toilet bowl to allow a user to sit on the toilet; a stool collection module for collecting stool samples from a subject using the toilet; an extraction module for extracting one or more biomarkers from the collected stool samples; a testing module for testing the one or more biomarkers to identify the presence of target RNA, DNA, proteins, and/or other biomarkers, e.g., viruses, such as SARS-CoV-2, cancers, and the like; and a sanitization module for sanitizing the toilet between users.

[00014] In accordance with yet another example, a method is provided for analyzing excreta of a subject using a toilet that includes collecting a stool sample after a subject has defecated in the toilet; extracting one or more biomarkers from the collected stool sample; testing the one or more biomarkers to identify the presence of target RNA, DNA, proteins, and/or other biomarkers, e.g., viruses, such as SARS-CoV-2, cancers, and the like; and sanitizing the toilet between users.

[00015] Other aspects and features of the present invention will become apparent from consideration of the following description taken in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[00016] It is believed the present invention will be better understood from the following description of certain examples taken in conjunction with the accompanying drawings, in which like reference numerals identify the same elements and in which: [00017] FIG. 1 A is a schematic showing an exemplary smart toilet, system, and method that may serve as a centralized diagnostic center that may provide automated stool sampling, e.g., with quick turnaround time for RNA testing, and with the toilet seat/surfaces being sanitized in between users. In the example shown, users may register with a health portal (e.g., which can be performed on a mobile device while on the toilet), which may then alert them to their test results (e.g., in under thirty (30) minutes), link them with medical care, provide advice and guidelines from designated physicians for isolation, and the like. Optionally, aggregate data may also be used for population surveillance to assess community burden.

[00018] FIG. IB is a schematic showing an exemplary network architecture of a system for processing and/or analyzing data from one or more smart toilet systems. [00019] FIG. 2 is a schematic showing a development plan for the smart toilet and system.

[00020] FIG. 3 A shows an example of a smart toilet device for monitoring and/or analyzing excreta of a user including a housing mountable to a toilet and a toilet seat. [00021] FIG. 3B is a schematic showing exemplary modules that may be included in the smart toilet device of FIG. 3 A. Alternatively, the modules of the smart toilet device may be integrated directly into a toilet.

[00022] FIG. 3C shows optional components or modules that may be included in the smart toilet device of FIG. 3 A for analyzing excreted biospecimens. For example, the toilet may include one or more devices for measuring one or more parameters related to voided urine and/or defecated stool of users, one or more devices for identifying users and/or their time and/or duration of use, and the like.

[00023] FIGS. 4A-4C show an exemplary systematic workflow for defecation monitoring using the smart toilet device of FIGS. 3A-3C.

[00024] FIG. 5 is a schematic showing an exemplary method for collection and preparation of stool samples using the smart toilet device of FIGS. 3A-3C.

[00025] FIG. 6 is a schematic showing an example of a viral RNA extraction module that may be included in the smart toilet device of FIGS. 3A-3C.

[00026] FIG. 7 shows an exemplary method for detection of SARS-CoV-2 RNA using ultrafast photonic PCR.

[00027] FIG. 8 is a schematic showing an exemplary sanitization module for sanitizing between users that may be included in a smart toilet device, such as that shown in FIGS. 3A-3C.

[00028] The drawings are not intended to be limiting in any way, and it is contemplated that various examples of the invention may be carried out in a variety of other ways, including those not necessarily depicted in the drawings. The accompanying drawings incorporated in and forming a part of the specification illustrate several aspects of the present invention, and together with the description serve to explain the principles of the invention; it being understood, however, that this invention is not limited to the precise arrangements shown.

DETAILED DESCRIPTION

[00029] The following description of certain examples of the invention should not be used to limit the scope of the present invention. Other examples, features, aspects, embodiments, and advantages of the invention will become apparent to those skilled in the art from the following description, which is by way of illustration, one of the best modes contemplated for carrying out the invention. As will be realized, the invention is capable of other different and obvious aspects, all without departing from the invention. Accordingly, the drawings and descriptions should be regarded as illustrative in nature and not restrictive. [00030] Before the examples are described, it is to be understood that the invention is not limited to particular examples described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular examples only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

[00031] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

[00032] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, some potential and exemplary methods and materials are now described.

[00033] It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a compound” includes a plurality of such compounds and reference to “the polymer” includes reference to one or more polymers and equivalents thereof known to those skilled in the art, and so forth.

[00034] Certain ranges are presented herein with numerical values being preceded by the term “about.” The term “about” is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number. [00035] Turning the drawings, FIGS. 1 A and IB show an example of a “smart toilet” system 104 and method for passive, non-invasive, longitudinal monitoring of fecal SARS- CoV-2 RNA as a potential biomarker of COVID-19 and/or other biomarkers and/or infections within a population of users or subjects 102. The COV-ID (Coronavirus Identification) toilet may be uniquely suited to the military population, as installing these units in shared bathrooms would ensure they are utilized by all service members in the unit, but it can also be easily installed onto existing toilets in the civilian population, e.g., in locations where multiple users may share a common set of toilets. The COV-ID toilet may allow for repeated, non-invasive testing of service members to identify infected individuals earlier and prevent outbreaks in these contained spaces. The system 104 may serve as a centralized diagnostic center, e.g., in a military or other context, to detect CO VID-19 (and/or other) infection and facilitate early diagnosis and isolation. Generally, tool sampling may be automated with quick turnaround time for viral RNA testing, and the toilet seat/ surfaces may be sanitized in between users.

[00036] For example, at 110 in FIG. 1 A, individual users 102 who use a smart toilet including the features described herein may have their feces automatically tested after each use, e.g., at 112. At 114, each individual may be notified of the results of their tests, e.g., shortly after using the toilet, e.g., using an application or other notification system on their cellphone or other electronic device, such as system 104 shown in FIG. IB. At 116, the smart toilet may automatically sanitize the toilet between users, as described further elsewhere herein.

[00037] At 120, test results from multiple users may be compiled and/or monitored, e.g., using the system 104 shown in FIG. IB, to provide information to the individual users and/or to third parties, e.g., medical personnel, supervisors, and the like, as described further elsewhere herein. For example, the system 104 may be used to process and/or analyze test results from one or more smart toilets 130 at a location 122, e.g., onboard a ship, at a military base, hospital, and/or other facility where multiple users share a common set of toilets, represented by building 122 in FIG. 1 A. Although only one toilet 130 is shown for simplicity in FIG. IB, it will be appreciated that multiple toilets 130 at a location 122 may be equipped with smart toilet systems such that all of the users 102 at the location 122 may be monitored and their data compiled by the system.

[00038] As shown in FIG. IB, the system 104 may include a server 140 and a database 142 that may receive results and/or other information from the smart toilet(s) 130, e.g., via network 144. The server 140 and database 142 may include one or more computer systems, e.g., including one or more processors, memory and/or storage devices, and communication interfaces (not shown) for communicating via the network 144, e.g., with the smart toilet(s) 130, with user electronic devices 150a-150n, and/or other parties involved in the methods performed by the system 104. The server 140 may include one or more hardware-based components and/or software-based modules for performing the various functions related to the methods performed, as described elsewhere herein. Although only one server 140 is shown, it will be appreciated that multiple servers (not shown) may be provided at the same or different locations that operate cooperatively to perform the functions described herein.

[00039] The network 144 may include one or more private and/or public networks, including a wide area network (“WAN”), a local area network (“LAN”), an intranet, a wireless network, a short messaging service (“SMS”), or a telephony network. For example, any such network may incorporate several different types of networks including a WAN, a LAN, and/or a wireless network within the location 122 and/or distributed at other locations. One such network including multiple different types of networks is the Internet. [00040] Each of the user electronic devices 150a-150n may be a desktop computer, a laptop computer, a mobile or cellular telephone, a tablet, a personal digital assistant, or other electronic device, capable of communicating via the network 144. Generally, each of the user devices 150a-150n may include one or more processors, memory and/or storage devices, communication interfaces, and/or user interfaces, e.g., a display, keyboard, mouse, touchscreen, and/or other types of interactive interfaces (voice, motion, etc.). For example, the interfaces may include one or more input devices, such as a microphone, keyboard, touchscreen, camera, and the like, and one or more output devices, such as a display, speaker, light indicators, and the like. Thus, the electronic devices may receive communications from the server 140 via the network 144, e.g., notifications of test results, warnings of outbreaks, and/or other notifications related to compiled tests and/or analyses and the like, as described further elsewhere herein.

[00041] Turning to FIG. 2, at 210, the smart toilets herein and the associated systems and methods may be used to acquire and analyze individual fecal samples, e.g., to quantify individual RNA levels of CO VID-19 or other target biomarkers. Optionally, the systems may correlate identified fecal viral load, e.g., from samples and associated data from the smart toilets, with symptom severity. As shown at 220, the smart toilets herein may include multiple modules, e.g., in one example, for stool sampling with a stamping method, isolation/purifi cation of SARS-CoV-2 RNA with magnetic beads, photonic PCR with ultrafast signal transduction, auto-sanitization, and integration with user electronic devices. The various processes performed by the toilet system may be automated so that the toilet system minimally interferes with ordinary human behavior. In one example, the expected turnaround time for users to be notified of their results is less than thirty minutes and/or otherwise to rapidly inform individual users if they test positive for infection, which may minimize exposure of other individuals and/or otherwise reduce spread of infection.

[00042] Turning to FIGS. 3A-3B, an exemplary modular toilet-mountable health monitoring device 310 is shown, which, optionally, in addition to modules for fecal analysis described herein, may include one or of the features and/or systems disclosed in incorporated by reference U.S. application Serial No. 16/506,942, e.g., providing for stool and/or urine form analyses, such as those shown in FIG. 3C.

[00043] Generally, as shown in FIGS. 3 A and 3B, the device 310 may include a housing 320 configured to be mounted to an existing toilet (not shown), e.g., in place of a conventional toilet seat. Optionally, a toilet seat 370 may be mounted to the housing 320, which may function as a conventional toilet seat but, optionally, may include one or more additional features, as described further elsewhere herein. For example, the housing 320 may include one or more mounts or fasteners (not shown), which may be used to secure the housing 320 at the back of a toilet such that the toilet seat 370 is positioned over the toilet bowl similar to conventional seats. Alternatively, the housing 320 and/or the modules may be permanently integrated into a toilet (not shown), e.g., with one or more of the modules and/or features mounted within and/or at desired locations relative to the toilet bowl of the toilet.

[00044] The housing 320 may include one or more processors or controllers (one processor 322 shown for simplicity), which may control operation of the various modules of the device 310. For example, the processor 322 may be coupled to modules or components of the device 310, e.g., a stool collection module 330, an extraction module 340, a testing module 350, and a sanitization module 360, as shown in FIG. 3B and described further below. In addition, the processor 322 may be coupled to a communications interface 324 within the housing 320, e.g., including a transmitter configured to communicate wirelessly, e.g., to the server 140 via the network 144 (shown in FIG. IB). [00045] Optionally, the device 310 may include one or more features for identifying when a user uses the toilet. For example, as shown in FIGS. 3 A and 4A-4B, one or more pressure sensors (one sensor 372 shown for simplicity) may be provided on the toilet seat 370, e.g., on the lower surface, such that the sensor(s) 372 may contact the toilet bowl when a user sits on the toilet. The pressure sensor(s) 372 may be coupled to the processor 322, e.g., such that, when the processor 322 receives signals from the sensor(s) 372 indicating when a user sits on the toilet seat 370, the processor 320 may activate one or more systems of the device 310 to monitor the user. Optionally, the processor 370 may use the signals from the sensor(s) 372 to monitor one or more parameters during use, e.g., such as length of time that the user is defecating and the like, as described further elsewhere herein.

[00046] In addition or alternatively, as shown in FIG. 3 A, one or more motion sensors 374 may be provided on the toilet seat 370, which may also be coupled to the processor 320, e.g., to detect when the seat 370 is raised or lowered. For example, if the processor 320 detects that the seat 370 is raised, the stool analysis modules may remain dormant, while if the processor 320 detects that the seat is lowered 370, the processor 320 may prepare the stool analysis modules for taking and testing a sample.

[00047] Further, in addition or alternatively, the device 310 may include one or more cameras 376, e.g., for monitoring use of the toilet. For example, a camera 376 may be oriented into the toilet bowl to acquire images of the contents of the bowl, e.g., during or after use. For example, as shown in FIG. 4C, the processor 320 may analyze images from the camera 376 to identify the location of a stool sample within the toilet bowl, which may be used to control operation of the stool collection module 330, as described elsewhere herein.

[00048] Optionally, the processor 320 may analyze images from the camera 376 to perform one or more analyses, e.g., to grade the subject’s stool, e.g., on the Bristol Stool Form Scale (BSFS) using an automated classifier using a machine-learning algorithm, and/or acquire images of discarded toilet paper, e.g., to identify colorimetric, fecal occult blood, and/or other changes for screening cancer and/or other conditions, as described in the Serial No. 16/506,942.

[00049] With additional reference to FIG. 3C, optionally, the device 310 may include one or more features for monitoring and/or analyzing other excreta, e.g., to perform urinalysis, uroflowmetry, and the like. For example, the device 310 may include one or more cameras that are coupled to the processor 320 such that the processor 320 may analyze video images of subject’s urine streams, e.g., using urofl owm etry to measure baselines and/or identify abnormal urine flow associated with diseases identifying individual users. In addition or alternatively, the device 310 may include a urinalysis module (not shown), e.g., including urinalysis strips that may be fed from a disposable cartridge to a movable stage, which may be deployed into the toilet bowl and into the stream of urine to collect a sample, which the device 310 may then analyze, e.g., as also described in the Serial No. 16/506,942.

[00050] Optionally, the device 310 may include a thermal imaging camera, which may be included in the housing 320 and/or seat 370, which may be oriented towards a subject sitting on the toilet, e.g., oriented to provide accurate body temperatures by thermally imaging the perianal area of seated users. Fever is the most common symptom among COVID-19 patients. Thus, routine body temperature monitoring may be useful for the timely detection of CO VID-19 or other infections. In a study describing 138 patients hospitalized with COVID-19 pneumonia in Wuhan, the most common clinical features at the onset of illness were fever over 100°F (99% of the enrolled patients).

[00051] Optionally, the device 310 may include one more sensors to measure oxygen saturation of users. Hypoxia is an indicator of severe CO VID-19 infection and CDC recommendations for in-home nursing care of symptomatic CO VID-19 patients include monitoring the oxygen saturation at least three times daily to identify and manage serious infections. Thus, including such a sensor on the device 310 may allow routine monitoring of oxygen saturation, which may serve as a “canary in a coal mine” for mounting COVID- 19 infection. For example, a photoplethysmography (PPG) sensor (not shown) may be provided on the seat 370, including an LED, photodiode, and microcontroller, to illuminate the tissue in the user’s thigh, which would be in full contact with the seat when sitting in order to provide accurate oximetry measurements from the toilet seat.

[00052] Optionally, the device 310 may include one or more components to identify users, e.g., to identify one or more biometric identifiers of individual subjects using the toilet, e.g., to distinguish and monitor multiple subjects. For example, a fingerprint reader may be provided, e.g., on the handle of the toilet (not shown), which may acquire a fingerprint before allowing the toilet to flush to identify the user. In addition or alternatively, a camera system may be provided for acquiring anal prints (anus wrinkle) of subjects using the toilet, which may facilitate securely associating collected data with each subject. [00053] Thus, the smart toilet device 310 generally uses the modules for collection and preparing stool sample, e.g., using a standard workflow for biochemical analyses of stool that includes four sub-processes including 1) sample collection, 2) sample preparation, 3) molecular recognition, amplification, and signal transduction, and 4) system integration.

Optionally, the device 310 and other smart toilet systems herein may be able to perform one or more additional functionalities such as biometric identification, real-time noncontact perianal thermometry, oximetry, and defecation monitoring with stool form analysis (already completed), e.g., integrated into the COV-ID toilet in order to gather personalized clinical data for effective COVID-19 screening. For example, if desired, the smart toilet may also perform one or more of the following functions.

[00054] 1) Standard urinalysis test: Test strips that screen for diseases ranging from urinary tract infection to liver dysfunction are mounted within the smart toilet and are programmed to interact with the urine stream. This removes the labor and error associated with manually dipping the strips.

[00055] 2) Urofl owmetry: Video analysis of the urine stream measures urinal baselines in order to identify abnormal urine flow associated with diseases such as benign prostatic hypertrophy and voiding dysfunction.

[00056] 3) Bristol Stool Form Scale (BSFS): Stool photos are collected in the smart toilet for grading on the BSFS using an automated classifier that has been developed in our lab through a machine learning algorithm.

[00057] 4) Time to first stool and total seating time: The device may also collect additional user information, such as various times of usage and time required to begin defecation post seating - information integral to clinicians for the management of conditions such as constipation and hemorrhoids.

[00058] 5) User identification: The smart toilet may use fingerprinting as well as

“anal-print identification” for non-contact biometric identification to securely associate the collected data to the user. Additional information regarding these functions may be found in application Serial No. 16/506,942.

[00059] Optionally, the smart toilet may be equipped with an Al to identify different forms of stool, including loose stool, e.g., using a deep convolutional neural network to classify stool in the toilet in situ, according to the BSFS, which categorizes stool types into seven forms. For example, “Type 1” is associated with severe constipation while “Type 7” is associated with severe diarrhea. The BSFS provides an objective scale to accurately communicate this information between patients and physicians. The BSFS classifications are especially valuable when many data points can be obtained in longitudinal monitoring. However, patient self-reporting of BSFS classifications has shown to have high variability and poor compliance. Demand for a more objective, passive, and reliable method to for stool classification are therefore needed especially for continuous monitoring in the military settings with crowded conditions. Therefore, a deep CNN may be trained using stool image files to classify stools based on the BSFS with high accuracy and/or perform other functions described elsewhere herein.

[00060] Returning now to FIGS. 3 A and 3B, the modules included in the device 310 may be configured for fecal sample collection and processing, RNA isolation and detection, e.g., with in situ ultrafast photonic polymerase chain reaction (PCR), and ultraviolet-C (UV- C) light-emitting diode (LED) sanitization. As described further elsewhere herein, the processor 322 may control the various modules and, optionally, may send text messages or wireless communications, e.g., via the interface 324 and network 144 to the server 140, e.g., to notify participants of results of their stool morphological analyses. Alternatively, at least some of the processes, e.g., analyzes of test results and/or communications with users and/or third parties may be performed by the server 140 and/or other systems separate from the smart toilet device 310, if desired, e.g., to reduce processing time and/or simplify hardware for the device 310.

[00061] Turning to FIG. 5, an exemplary stool collection module 330 and associated method are shown, which may be used to collect individual stool samples from users of a smart toilet 130. In the example shown, the stool collection module 330 is a stamping module that includes a stamping mold or vial 332 that may be controlled by the processor 322, e.g., coupled to and operating a linear or other actuator (not shown) to acquire a stool sample for processing. For example, the stamping mold 332 may be an elongate tubular, e.g., cylindrical, body including an open end 334 that may be advanced into stool 90 within the toilet (not shown) to direct a sample 90a into the interior chamber 336 of the mold 332, e.g., as shown in Step 5A. In one example, the collection module 330 may use a linear actuator, e.g., including a ratchet and a gear attached to a motor, that stamps the stool 90 with a vertical motion of the mold 332.

[00062] Alternatively, the stool collection module 330 may include a mechanical actuator carrying a swab, e.g., similar to a nasopharyngeal swab (not shown), which may be used to collect a stool sample, e.g., during a defecation event as the stool is dropping into the toilet. For example, the actuator may include a mechanical arm (not shown), which may be extended into the stool path of the subject within the toilet bowl during defecation, e.g., while an optical sensor, camera, or other device records the event. The actuator may be configured to then transfer the swab into a vial or other container (also not shown), which may include a solution, e.g., including a lysis buffer, for processing, similar to the stamping module described above.

[00063] Optionally, the processor 322 may be coupled to a camera, e.g., camera 376 shown in FIG. 3B, which may be oriented into the toilet bowl to allow the processor 322 to identify the location of the stool 90 and direct the end 334 of the mold 332 (or swab) into the stool 90 to collect the sample 90a.

[00064] The sample collection module 330 generally uses three steps: (a) collection, (b) homogenization, dissolution, and cell lysis, and (c) filtration and suction. For example, after stamping, the stool sample 90a may then be processed, e.g., homogenized within a cylindrical sonicator or other device through pulses of ultrasonic excitations, e.g., as shown in Step 5B. For example, if the mold 332 captures the stool sample 90a in a pre-formed cylinder structure, a ring piezoelectric transducer or other sonicator may be used, (e.g., having an Outer Diameter 25.4 x Inner Diameter 22.1 x Height 12.7 mm, 37 kHz resonant frequency, such as Model SMC25D22H12PLS, by Steminc).

[00065] A buffer 338 may be added to the sample 90a within the interior 336, and the sonicator may then apply vibration to the vial 332 for a desired time, e.g., ten to fifteen (10- 15) minutes to perform active lysis, thereby producing a homogenized stool sample 90b. In one example, a mixture of homogenization and lysis buffer containing ribonuclease (RNase) inhibitors and deoxyribonuclease (DNase) may be applied through a PVC tube for homogenization. The sonication is then performed through pulses of excitations and thermoelectric (Peltier) cooler for efficiently homogenizing the sample while avoiding any RNA degradation.

[00066] After the sonication step, the liquefied lysate enclosed in the ring cylinder may then be filtered, e.g., using a ten-micron filter and transported to the downstream analysis module. The collection and preparation module may then self-clean itself, e.g., via ultrasonic pulses of the sonicator in the presence of bleach. Optionally, since the stool liquidity may play a key role in the sample collection module, the system may calibrate and optimize sample collection duration according to the determined BSFS by the Al. [00067] In one example, at Step 5C in FIG. 5, the supernatant sample 90b may be transported to the RNA extraction module 340 and testing module 350 for testing. For example, suction may be applied to the interior 336 to draw the homogenized sample 90b into a separate preparation and/or testing chamber within the device 310 or, alternatively, the sample 90b may tested within the collection vial 330 without transfer. Optionally, the sample 90b may be filtered during the transfer to the extraction module 340.

[00068] Within the extraction module 340, nucleic acid amplification tests (NAATS) may be performed on the homogenized stool sample 90b. Optionally, the RNA may be purified, e.g., via a magnetic bead -based RNA extraction method as shown in FIG. 6, e.g., as described further at -and--size-- selection/pcr/perfonnance, the entire disclosure of which is expressly incorporated by reference herein.

[00069] After transporting the homogenized sample, the stool collection module 330, e.g., including the interior 336 and distal end 334 of the stamping tool 332, mechanical arm or actuator, and/or other desired components, may then self-clean itself, e.g., using one or more processes, such as ultrasonic pulses and/or bleach. Because the SARS-CoV-2 virus (and other viruses) can linger on surfaces for up to three days, the system may include a self-sanitization module 360, e.g., including one or more UV-C LEDs for the sanitization of the COV-ID toilet’s surfaces to prevent transmission and cross-contamination between users. Optionally, the toilet may include a lid configured to automatically close during flushing to prevent aerosol toilet plumes that may lead to oral-fecal transmission.

[00070] Optionally, the RNA extraction module may be enclosed in a disposable cartridge, e.g., that may be removed and replaced automatically between users.

[00071] Within the testing module 350, the extracted RNA may then be tested to identify one or more biomarkers to identify the presence of one or more target RNA, DNA, and/or proteins, e.g., to identify SARS-CoV-2 RNA with magnetic beads. In one example, the testing module 350 is configured to use photonic PCR with ultrafast signal transduction to identify the target biomarkers.

[00072] In an exemplary method, the system may target four different genes (RdRp, E, Nl, and N2) for SARS-CoV-2 detection, e.g., using systems and methods, such as those available from Kryptos Biotechnologies, Inc. Ultrafast photonic PCR is ideal for point-of- care (POC) testing (detection of viral RNA in under 10 minutes, turn-around time (TAT) under 30 minutes, and under $10 per test), and sample-to-answer instruments with disposable microfluidic cartridges may be mounted in the toilet system. The sample from the upstream module is automatically transported to this module with a controlled syringe pump.

[00073] Turning to FIG. 4, the smart toilet device 310 may include a defecation monitoring module equipped with an Al, as described elsewhere herein, to classify stools of individual subjects in real-time and in situ. Through this module, the system may collect one or more parameters related to a user, e.g., the user’s defecation time, first stool dropping time, total seating time, and associated BSFS. By collecting these supplementary data (e.g., temperature, oxygen saturation, defecation timings, and stool morphology) in tandem with COVID-19 fecal testing, the system has the potential to generate individual risk assessment profiles for COVID-19 infection.

[00074] For example, as shown in FIG. 4A, as a user sits on the toilet for a defecation event, a pressure sensor 372 below the toilet seat initiates a defecation monitoring camera 376, such as that shown in FIG. 4B. The camera may then record the inside of the toilet bowl until the end of the defecation event. The collected images are then fed into deep CNN layers for stool classification, e.g., as shown in FIG. 4C.

[00075] The resulting data acquired by the device 310 may be communicated to the server 140 for storage within the database 142 and/or for further analysis, if desired. The server 140 and database 142 may securely store the data, e.g., to preserve the privacy of individual users, while allowing analysis, e.g., to identify outbreaks and/or other trends. [00076] Optionally, an Al within the device 310 and/or the server 140 may calibrate and/or optimize sample collection and/or analysis. For example, it may be desirable to demonstrate on-chip lysis efficiency of greater than ninety percent (90%) with the spiked synthetic SARSCoV-2 RNA in healthy fecal samples. A table of annual target performances is shown in Table 1 below. The aim is to achieve 95% of stool collection repeatability, five minutes of homogenization time, and 90% of lysis efficiency by the end of the funding period.

Table 1. Fecal Sample Collection and Preparation Module Specifications

[00077] The lysate consists of the target SARS-CoV-2 viral RNA along with unnecessary debris that may hinder downstream applications. The efficiency of extracting, enrichment, or purifying biomarkers may be a key parameter that impacts the limits of analyte detection. To improve the downstream analysis, the extraction module 340 may use a microfluidic-based magnetic bead RNA extraction method to purify the RNA and remove the debris, e.g., as shown in FIG. 6. The magnetic-bead-based method with the solid phase reversible immobilization (SPRI) technology allows the magnetic beads to extract RNA only. The carboxyl -coated magnetic beads adsorb RNA in the presence of polyethylene glycol (PEG), which may then be isolated with an external magnet. While isolated, repeated cycles of washing steps remove the debris and purify the RNA strands. The purified RNA strands are then transported to the detection or testing module 350. The performance of RNA extraction may be evaluated using spiked viral RNA in health fecal samples via the extraction performance and the quality of RNA from off-chip PCR analysis of the house-keeping genes (e.g., bacterial 16S rRNA and human RNaseP gene); the aim is to achieve >80% of RNA extraction yield. The detailed annual target performances are listed in Table 2 below.

Table 2. SARS-CoV-2 Signal Transduction Specifications

[00078] The sub-processes following the sample collection and preparation steps may include 1) molecular recognition, amplification, and signal transduction of biomarkers to a readable output, and 3) system integration. In the molecular recognition, amplification, and signal transduction module, ultrafast photonic PCR may be used that enables rapid development and production of molecular assays for newly identified analytes of in the toilet system. Ultrafast photonic PCR may be cost-effective, rapid (15 minutes and under $50), and features low power consumption, compact size (smaller than a penny), and simple operation.

[00079] Plasmon-excited gold (Au) film is capable of rapidly heating the surrounding solution to over 150 °C within three minutes. Using this method, ultrafast thermal cycling (30 cycles; heating and cooling rate of 12.79 ± 0.93 °C s-1 and 6.6 ± 0.29 °C s-1, respectively) from 55°C (temperature of annealing) to 95°C (temperature of denaturation) is accomplished within five minutes. As shown in FIG. 7, using photonic PCR thermal cycles, nucleic acid (SARS-CoV-2 RNA) amplification may be performed within fifteen (15) minutes with the LOD of a few copies of analyte/pL for in vitro testing. The target was the SARS-CoV-2 N2 gene and the approach was benchmarked against a CDC standard (PCR thermal cycler: ABI StepOnePlus, total 75 minutes), wherein our method shows better performance. This module was also tested with MRSA, which showed a similar assay time (8 minutes) and similar LOD (a few copies of analyte/pL). This simple, robust, and low- cost approach to ultrafast PCR using an efficient photonic-based heating procedure will be integrated into the COV-ID toilet. The aim is to achieve a TAT of less than 10 minutes and LOD of ~10 copies/pL with >95% detection accuracy of SARS-CoV-2 RNA. A potential pitfail for this approach is that it may not tolerate sample contamination potentially in various stool matrices/environments. If this is the case, a magnetonanosensor method may be employed, which offers matrix -insensitive detection of the analyte of interest.

[00080] The results of individual tests may be communicated by the device 310 to the server 140 for further storage and/or analysis. As described elsewhere herein, each individual may receive a communication from the server 140 (or directly from the device 310) including information related to their test results.

[00081] User identification in the toilet system may be particularly useful as the system is expected to be shared amongst many different individuals, especially in a military setting. To achieve longitudinal monitoring of SARSCoV-2 viral RNA levels and symptoms, each toileting event and its associated parameters may be logged and associated with the user. For example, a fingerprint scanner may be installed on the toilet handle, which may provide reasonable user identification, e.g., to an accuracy of about 95%, although the handle may potentially serve as a fomite for viral transmission between users. [00082] Alternatively, a touch-free identification method may be used instead, e.g., utilizing an anal-print, which is unique to an individual, e.g., as disclosed in application Serial No. 16/506,942. For example, a scanner may be installed to record a short video clip of the user’s anus. The region of interest (RO I), the anus, may then be identified using an image recognition algorithm (template matching). For example, a deep neural network (Google Inception V3 CNN) may be used that compares input images with the reference images stored in the system for human anus identification or a residual neural network (ResNet) may be sued, which may provide a more accurate model in image classification. The targeted performance level may be at least reaching 95% accuracy; however, if desired, additional algorithms such as the mean squared error (MSE) and the structural similarity index measure (SSIM) may be employed.

[00083] COVID-19 can potentially be transmitted through a fecal-oral route, whether through direct contact (the SARS-CoV-2 virus can linger on surfaces for up to three days), or through aerosol via toilet plumes generated by flushing. While good personal hygiene (e.g., hand-washing, closing the toilet lid before flushing) is highly encouraged, optionally, the devices and systems herein may include proactive countermeasures to prevent the fecal- oral transmission of CO VID-19 between different COV-ID toilet users. For example, a toilet lid may be mounted to the housing 320 of device 310 to replace a conventional toilet lid. A motorized actuator may be coupled to the lid designed to automatically close the lid after each use, e.g., before flushing, to prevent aerosol toilet plumes and minimize physical contact with the toilet surfaces. In addition or alternatively, the toilet may flush automatically with user motion detection.

[00084] In addition or alternatively, as shown in FIG. 8, the system may include one or more UV-C light-emitting diodes for ultraviolet germicidal irradiation (UVGI, disinfection application) of various surfaces of the toilet. UV-C has a wavelength between about one hundred and two hundred eighty nanometers (100 and 280 nm). The germicidal action is maximized at 265 nm with reductions in germicidal effectiveness on either side of spectrum. Commercially available UVGI have already demonstrated efficient sterilization and disinfection up to 99.9% removal of pathogens within in a short time of a few minutes based on the D-values or decimal reduction times (doses) for coronaviruses are 7 - 241 J/m2 (mean: 67 J/m2) and the consuming power from about twenty to thirty milliWatts (20 to 30 mW) is expected per UV-C LED strips. [00085] In addition, to minimize the users’ exposure to UV-C irradiation, motion sensors that detect human motion and behavior may be provided that allow the toilet lid to be locked and closed during the UV-C irradiation and automatically re-open when the system is ready.

[00086] Optionally, the smart toilets described herein may be a mountable attachment that can be fitted onto existing toilets, similar to a bidet seat. Optionally, all or a desired portion of the collected data (BSFS, body temperature, viral RNA load, and oxygen saturation level) may be regarded as patient health information (PHI) and properly annotated with users’ identification, which may be wirelessly transmitted, curated with their medical history and stored in an online health portal, e.g., maintained by the server 140 and database 142 shown in FIG. IB.

[00087] Optionally, the system 104 may provide an integrated health portal, e.g., including a REDCap-compatible cloud system to autonomously integrate and collect smart toilet data, perform risk assessment, identify clinical and practice workflow for data conversion, and combine continuous monitoring data with the Electronic Health Record (EHR). Interactive features of the health portal may be provided for participant engagement and to enable access to study clinicians.

[00088] For example, a mobile application may be provided that is compatible with smart phone environments (e.g., Android and iOS), which may be downloaded onto user devices 150a-150n, e.g., to identify each individual with every flush, and evaluate the quality of data measures prior to EHR integration. A comprehensive security solution may be provided without compromising end-user’s experience by investigating various network issues such as traffic analysis, session hijack, unauthorized access, and eavesdropping. Complicated clinical laboratory methods and instruments requiring skilled operators and CLIA designated moderate/high complexity facilities are not suitable for military settings. Therefore, integrated instruments requiring limited skill for operation is imperative. The various metrics to be analyzed are shown in Table 3 below, including sensitivity, specificity, limit of quantification, reproducibility, throughput, and size of the smart toilet, weight of the smart toilet, power, and consumables cost per biospecimen.

[00089] Although the devices, systems, and methods herein are described with particular reference to identifying the presence of SARS-CoV-2 RNA, it will be appreciated that the devices, systems, and methods may be used to identify the presence of other biomarkers, such as RNAs, DNAs, proteins, and the like, e.g., to identify various viruses, cancers, and the like. For example, other bioassays may be included in the devices and systems herein to test stool samples in addition to or instead of the PCR devices described herein.

[00090] Further, in describing representative embodiments, the specification may have presented the method and/or process as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. As one of ordinary skill in the art would appreciate, other sequences of steps may be possible. Therefore, the particular order of the steps set forth in the specification should not be construed as limitations on the claims.

[00091] While the invention is susceptible to various modifications, and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should be understood, however, that the invention is not to be limited to the particular forms or methods disclosed, but to the contrary, the invention is to cover all modifications, equivalents and alternatives falling within the scope of the appended claims.