Saliva collection and testing system

Abstract

A system with a saliva sampling device configured to be worn in a patient's mouth. The saliva sampling device is a polymer retainer or polymer orthodontic appliance. A saliva analysis engine is used to associate one or more analytes from one or more saliva samples with one or more health attributes. A health monitoring engine updates the patient's health profile based on the associated health attributes.

Description

[0001] Cross-reference to related applications

[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 932,396, filed November 7, 2019, which is incorporated herein by reference. Background Technology

[0003] For example, in the field of proteomics, recent and ongoing advances have led to the discovery of new fluid-borne biomarkers for the prediction and diagnosis of various diseases. Blood is the traditional fluid for many pathological biomarker tests. However, blood samples can be difficult to process, especially when attempting to isolate analytes of interest, such as specific proteins. Relatively large amounts of blood are typically required due to the filtration and separation steps involved in the process. Furthermore, many patients are reluctant to have their blood samples collected due to the negative reactions associated with needle puncture.

[0004] Other bodily fluids, such as urine and saliva, can also contain biomarkers. Saliva, in particular, has been a subject of much cutting-edge research aimed at identifying novel biomarkers. Notably, one publication reported that 2290 different proteins in saliva have been compiled, nearly 40% of which are considered biomarkers for diseases such as cancer, cardiovascular disease, and stroke, and can be found in saliva. See Loo et al. “Comparative human salivary and plasmaproteomes.” Journal of dental research vol.89,10(2010):1016-23.

[0005] Providing a saliva sample is a relatively simple procedure, involving spitting it into a tube or swabbing the mouth. Because no needle is needed to provide the sample, most patients do not experience the same negative reactions when providing a saliva sample as when providing a blood sample. In many cases, patients can provide saliva samples outside of the point of care. For example, publicly accessible genetic testing companies (such as 23andMe) can do so. TM Genetic testing is conducted using saliva by providing customers with mail-mailable spittoons.

[0006] For some analytes carried by saliva, saliva is considered a "real-time" fluid representing health status at the time of collection, due to the way it is constantly produced, unlike blood circulating in a closed system. (Al Muhtaseb, "Serum and saliva protein levels in females with breast cancer." Oncology Letters 8.6(2014):2752-2756). Therefore, due to the timing of sample collection, a particular saliva sample may not provide a high degree of confidence in overall health. However, periodically spitting into collection tubes or collecting oral swabs can be invasive and present patient compliance issues. Therefore, it would be useful to have a method that allows for saliva sampling on an extended basis with minimal patient interaction. Summary of the Invention

[0007] Implementations of systems, methods, and devices for tracking patient health using saliva sampling devices are disclosed, which can sample saliva over extended time periods.

[0008] Some implementations involve a method in which at least one analyte from at least one saliva sample can be associated with at least one health attribute. Saliva can be collected from a saliva sampling device configured to be worn in a patient's mouth. A patient's health profile can be updated based on at least one health attribute.

[0009] Some implementations relate to a system that may include a saliva analysis engine that can be configured to associate at least one analyte of at least one saliva sample with at least one health attribute.

[0010] In some implementations, saliva can be collected from a saliva sampling device configured to be worn in the patient's mouth.

[0011] In some implementations, the health monitoring engine can be configured to update a patient’s health profile based on at least one health attribute received from the saliva analysis engine.

[0012] In some implementations, a health profile may include at least one profile of at least one health condition, and at least one health attribute may be used to update at least one status profile.

[0013] In some implementations, a health profile may include at least one risk profile for at least one disease, and at least one associated attribute may be used to update at least one risk profile.

[0014] In some implementations, a health profile may include at least one nutritional profile in at least one nutritional aspect, and at least one health attribute may be used to update at least one nutritional profile.

[0015] In some implementations, at least one saliva sample may be collected by the saliva sampling device during the extended period of wear by the patient.

[0016] In some implementations, at least one saliva sample can be collected by the saliva sampling device over multiple days during the incremental wearing period of the device by the patient.

[0017] In some implementations, each period of incremental wearing can be at least one hour.

[0018] In some implementations, at least one saliva sample may be one of multiple saliva samples collected by a saliva sampling device over multiple days.

[0019] In some implementations, at least one health attribute may be processed to provide one or more of the following: nutritional information, disease information, hormone information, health information, and genetic information.

[0020] In some implementations, nutritional information may include one or more of the following: hydration information, pH information, fluoride information, mineralization information, alcohol information, and microbiome information.

[0021] In some implementations, disease information may include one or more of the following: infectious disease information, cancer information, inflammation information, and / or virus information.

[0022] In some implementations, disease information may include indicators of bodily function, such as hydration levels and cell permeability.

[0023] In some implementations, saliva biomarkers can also indicate the relative functional levels of various systems in the body.

[0024] In some implementations, at least one health attribute may include an indicator of hydration level.

[0025] In some implementations, at least one health attribute may include an indicator of cell permeability.

[0026] In some implementations, at least one health attribute may include indicators of the health status of the digestive system.

[0027] In some implementations, at least one analyte may represent at least one biomarker of at least one saliva sample.

[0028] In some implementations, at least one analyte can be received from a saliva testing system configured to test for the presence of at least one analyte in at least one saliva sample.

[0029] In some implementations, the saliva sampling device can wirelessly transmit data to a saliva analysis engine, and the data may or may not indicate at least one analyte.

[0030] In some implementations, the gene engine can be configured to associate at least one analyte of at least one saliva sample with at least one genetic attribute.

[0031] In some implementations, the logging engine can store health profiles.

[0032] In some implementations, the health monitoring engine can be configured to provide health monitoring updates and / or alerts to at least one access device.

[0033] In some implementations, the health monitoring engine can be configured to identify one or more health conditions and provide recommendations on products and / or medicines to address one or more health conditions.

[0034] In some implementations, the saliva sampling device may include one of the following: a retainer and an orthosis.

[0035] In some implementations, the saliva sampling device may be one of a plurality of saliva sampling devices.

[0036] In some implementations, a health profile can be updated and maintained based on multiple associated health attributes derived from multiple saliva samples collected by multiple saliva sampling devices.

[0037] In some implementations, the saliva sampling device may include at least one sensor.

[0038] In some implementations, the saliva sampling device may include at least one biosensor.

[0039] In some embodiments, saliva, wherein the saliva sampling device may include one or more saliva storage portions configured to store saliva.

[0040] In some implementations, at least one sensor may be configured to detect biomarkers.

[0041] In some embodiments, the saliva sampling device may include at least one sensor and at least one communication device coupled to the sensor.

[0042] In some implementations, at least one communication device may be configured to wirelessly connect to a network and / or a network access device.

[0043] In some implementations, the saliva sampling device can be shaped to fit the surface of a set of teeth.

[0044] In some implementations, the sampling device can be configured to collect and store saliva over multiple days.

[0045] In some implementations, the saliva sampling device may include at least one microfluidic channel.

[0046] In some implementations, the saliva sampling device may include at least one microfluidic chamber.

[0047] In some implementations, the saliva sampling device may include at least one microfluidic pump.

[0048] In some embodiments, the saliva sampling device may include an absorbent material.

[0049] In some embodiments, the absorbent material may include at least one absorbent member.

[0050] In some implementations, the absorbent material may include multiple absorbent components.

[0051] In some embodiments, the absorbent material may include membranes, paper, cloth, superabsorbent polymers, and / or hydrogels.

[0052] In some embodiments, the saliva sampling device may include a base layer shaped to fit onto a set of teeth, and a sampling layer shaped to fit the base layer and configured to collect saliva.

[0053] In some embodiments, the saliva sampling device may include a top layer shaped to fit onto the sampling layer.

[0054] In some implementations, the saliva sampling device may include at least one circuit.

[0055] In some implementations, at least one circuit can be triggered by detecting a biomarker.

[0056] In some implementations, the saliva sampling device may include a communication device.

[0057] In some implementations, the saliva sampling device can be adapted to provide an alarm when triggered by the detection of a biomarker.

[0058] In some implementations, the saliva sample contains biomarkers related to the human reproductive system.

[0059] In some implementations, biomarkers can be associated with pregnancy confirmation, fetal sex, fetal health, patient ovulation status, and patient fertility status. Attached Figure Description

[0060] The following detailed description, which will be read in conjunction with the accompanying drawings, describes some implementation methods:

[0061] Figure 1 A schematic diagram of a saliva sampling and testing system according to some embodiments is shown;

[0062] Figure 2 A flowchart of a method for maintaining a health profile according to some embodiments is shown;

[0063] Figure 3A A projection diagram of a saliva sampling device according to some embodiments is shown;

[0064] Figure 3B A schematic diagram of a saliva sampling device according to some embodiments is shown;

[0065] Figure 4A An exploded view of the material stack according to some embodiments is shown;

[0066] Figure 4B An exploded view of a saliva sampling device according to some embodiments is shown;

[0067] Figure 4C An exploded view of the material stack according to some embodiments is shown;

[0068] Figure 5 The process for forming a saliva sampling device according to some embodiments is shown; and

[0069] Figure 6 A schematic diagram of a computer system according to some implementations is shown.

[0070] The accompanying drawings depict various embodiments of the invention for illustrative purposes only, wherein the same reference numerals are used to identify the same elements. Those skilled in the art will readily recognize from the following discussion that alternative embodiments of the structures and methods shown in the drawings may be employed without departing from the principles of the invention as described herein. Detailed Implementation

[0071] Before describing the invention in more detail, it should be understood that the invention is not limited to the specific embodiments described, and therefore may vary. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not restrictive, as the scope of the invention will be limited only by the appended claims.

[0072] Where numerical ranges are provided, it should be understood that, unless the context explicitly specifies otherwise, each tenth of a unit from the lower limit of an intermediate value to the upper limit of the range, between the upper and lower limits of the range and any other specified or intermediate value within the range, is included in this invention. The upper and lower limits of these smaller ranges may be independently included within the smaller range and also within this invention, but are subject to any specific exclusions within the range. Where the range includes one or both limitations, the range excluding one or both of those included limitations is also included in this invention.

[0073] Unless otherwise defined, 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 pertains. Although any methods and materials similar to or equivalent to those described herein may also be used in the practice or testing of this invention, representative illustrative methods and materials are described hereafter.

[0074] Note that, as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural indicators unless the context clearly specifies otherwise. It should also be noted that claims may be drafted to exclude any optional elements. Therefore, this statement is intended to serve as a priori basis for the use of proprietary terms such as “unique” or “only” when referencing claim elements or using the “negative” limitation.

[0075] As will be apparent to those skilled in the art upon reading this disclosure, each individual embodiment described and illustrated herein has discrete components and features that can be readily separated from or combined with features of any of the other several embodiments without departing from the scope or spirit of the invention. Any enumerated method may be performed in the order of the enumerated events or in any other logically possible order.

[0076] Figure 1 A system 100 for maintaining a patient's health profile based on saliva sampling is illustrated. System 100 includes one or more saliva sampling devices 102 configured to sample a patient's saliva when worn in the mouth. In some embodiments, the saliva sampling device 102 is configured to perform more than one primary function. For example, the saliva sampling device 102 may include the basic structure of a tooth-mountable orthodontic polymer appliance (e.g., an INVISALIGN appliance) or a tooth-mountable orthodontic polymer retainer (e.g., an ESSIX ACE). The advantage of a saliva sampling device 102 with two functions is that the patient will wear the saliva sampling device 102 continuously (i.e., daily, half-day) for extended periods (e.g., more than 1 hour, 1-8 hours, etc.) for personal health or appearance reasons. Therefore, when the saliva device 102 is incorporated into a multifunctional device, patient compliance may be greater as the patient follows an orthodontic regimen.

[0077] In some embodiments, the patient does not require orthodontic treatment but desires to use the saliva sampling device 102. For such patients, a retainer or orthodontic appliance can be constructed based on the current position of the patient's teeth. Although such a saliva sampling device 102 does not have the secondary function of moving or maintaining tooth position, for the purposes of this disclosure, such a saliva sampling device 102 may still be referred to as a retainer and / or orthodontic appliance.

[0078] Some embodiments of the saliva sampling device 102 are configured to collect one or more saliva samples over an extended period of time. In some embodiments, the saliva sampling device 102 may collect discrete saliva samples corresponding to a specific wearing period. In other words, each time the saliva sampling device 102 is worn, it may collect separate samples or single samples. In some embodiments, the saliva sampling device 102 may collect continuous saliva samples that are not discretely stored within the saliva sampling device 102. In other words, each time the saliva sampling device 102 is worn, it may incrementally add saliva to a collection container configured to be slowly filled over time, such that the resulting saliva sample is a collection of multiple sampling periods.

[0079] Some embodiments of the saliva sampling device 102 include one or more of the following: a channel, a microfluidic channel, a chamber, a microfluidic chamber, an absorbent material, a preservative, a chemical and / or drug container, a pump, a processor, a sensor, a biosensor, and a communication device. Specific aspects of the saliva sampling device 102 are disclosed below.

[0080] In some embodiments, saliva sampling device 102 is one of a plurality of saliva sampling devices used for continuous tracking of a patient's health status. Therefore, in some embodiments, saliva sampling device 102 may be returned to the care provider for testing after a period of use (e.g., 1-2 months), after which the patient may wear a new saliva sampling device. This can be performed indefinitely to provide health tracking throughout the patient's life.

[0081] System 100 may include multiple submodules and / or subsystems, which may be referred to as modules for simplicity. Such modules may be implemented using hardware, firmware, and / or software contained on a non-transitory computer-readable medium executed by underlying hardware (such as one or more processors). For example, such a module may represent code contained on a non-transitory computer-readable medium that instructs the processor of system 100 to perform corresponding actions. Such modules may include: a health monitoring system 104, a saliva analysis engine 106, a health monitoring engine 108, a gene engine 110, a recording engine 112, a saliva testing system 114, and a recording access device 116. Modules may be considered optional, addable, and / or removable from system 100. For example, in some embodiments, the health monitoring system 104 does not require the recording access device 118 to operate. Similarly, in some embodiments, the saliva testing system 114 is used only for saliva sampling devices 102 that lack sensors and / or communication devices.

[0082] The health monitoring system 104 can be configured to receive data, which may be raw data sent by the saliva sampling device 102 and / or processed data from the saliva testing system 114, associate the processed data with one or more health attributes, and maintain the patient's health profile by updating the health profile with the health attributes. In some embodiments, the health monitoring system 104 may associate the processed data with one or more genetic attributes and maintain the patient's health profile by updating the health profile with the genetic attributes. The health monitoring system 104 may include one or more engines, such as a saliva analysis engine 106, a health monitoring engine 108, a genetic engine 110, and a recording engine 112.

[0083] If the saliva testing system 114 has not yet processed the data, the saliva analysis engine 106 can process the data to determine the type, presence, relative concentration, ratio, and / or quantity of one or more analytes that can be used as biomarkers. In some embodiments, multiple analytes can be identified. Such analytes may include proteins, cytokines, chemokines, interleukin-6, interleukin-1β, tumor necrosis factor-α, C-reactive protein, transferrin, histamine, histones, cells, molecules, alcohol, nanoparticles, chemicals, bacteria, enzymes, drugs, antibodies, metals, minerals, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), viruses, peptides, hormones, chromogranin A, cortisol, melatonin, testosterone, amylase, α-amylase, cotinine, neopterin, estrogens, estradiol, estriol, estrone, dinoprostone, insulin, carbohydrate components. Ingredients, polysaccharides, matrix metalloproteinase 8, metallopeptidase inhibitor 1, interleukin-1β, interleukin-6, interleukin-8, progesterone, 17OH-progesterone, 17α-hydroxyprogesterone, aldosterone, steroids, dehydroepiandrosterone, dehydroepiandrosterone sulfate, secretory immunoglobulin A, monocyte chemoattractant protein-1, epidermal growth factor, nerve growth factor, substance P, glutamate, calcitonin gene-related peptide, brain-derived neurotrophic factor, androstenedione, oxytocin, acids, nucleic acids, lipids, uric acid, galactose, glucose, mannose, fucose, microorganisms, biological communities, electrolytes, glycoproteins, and salts.

[0084] In some implementations, the saliva analysis engine 106 can evaluate the collected data to perform performance and / or diagnostic analyses of the saliva sampling device 102. For example, such analyses may include determining wear compliance and saliva sampling effectiveness based on the total amount of saliva collected.

[0085] In some implementations, the saliva analysis engine 106 can be configured to correlate the type, presence, relative concentration, ratio, and / or quantity of one or more analytes with one or more known biomarkers of pathology, condition, or health status to determine one or more health attributes. Health attributes may include nutritional information, disease information, hormonal information, genetic information, hydration information, pH level information, fluoride information, mineralization information, alcohol information, microbiome information, infectious disease information, cancer information, inflammation information, and / or viral information. Biomarkers carried in saliva are associated with a variety of diseases, viral infections, bacterial infections, parasites, physical injuries, inflammation, nutritional imbalances, hormonal imbalances, hormone levels, menstrual cycles, adrenal disorders, diabetes, asthma attacks, cancer, stress, fertility, pregnancy status, fetal sex, fetal health, ovulation status, fertility, and other health problems.

[0086] Examples of saliva-borne biomarkers are found in: Loo et al., Supra; Ilea, Aranka et al. “Saliva, a Magic Biofluid Available for Multilevel Assessment and a Mirror of General Health-A Systematic Review.” Biosensors vol. vol.26,4(2013):781-91; Mishra et al., “Recent advances in salivary cancer diagnostics enabled by biosensors and bioelectronics.” Biosensors&Bioelectronics 2016;81:181-197; and Lorenzo-Pouso, et al., “Protein-Based Salivary Profiles as Novel Biomarkers for OralDiseases,”Disease Markers,vol.2018,Document ID 6141845, page 22, 2018, all of the above are incorporated herein by reference.

[0087] The health monitoring engine 108 can access the recording engine 112 to retrieve patient health profiles and update the profiles based on one or more associated health attributes. In some embodiments, the health profile can be a statistically based model of one or more pathologies. The health profile can be determined by one or more algorithms. The health profile can provide one or more of the following for one or more health attributes: status, risk, probability, trend, intensity, level, and quantity. The patient health profile can include data on past diagnostic tests (e.g., blood / serum tests, saliva tests), health event records, genetic information, ancestry, psychological information, prescription drug use, illicit drug use, alcohol use, smoking history, age, weight, race, environmental exposure history, and family health history. In some embodiments, the patient health profile can be updated in parallel from other sources, for example, by a wearable device that records daily activities, heart rate, etc. In some embodiments, the patient health profile can be updated in parallel from other anonymizable patient health profiles that share similar genetic profiles, ancestry, living and / or working in the same neighborhood, sharing similar lifestyles, and / or being directly related to the patient. When making conclusions and recommendations based on detected biomarkers, system 100 can weight and consider some or all of these data points.

[0088] In some implementations, a health profile may consist of several sub-profiles derived from information based on associated health attributes. Sub-profiles may be statistically based models of specific pathologies. Each sub-profile may be determined by one or more algorithms. Each sub-profile may provide one or more of the following for a health attribute: state, risk, probability, trend, intensity, level, and quantity. Such sub-profiles may include nutritional profiles, disease profiles, hormone profiles, genetic profiles, hydration profiles, pH profiles, fluoride profiles, mineralization profiles, alcohol profiles, microbiome profiles, infectious disease profiles, cancer profiles, inflammation profiles, and / or viral profiles.

[0089] In some embodiments, the saliva analysis engine 106 can be configured to perform predictive analyses to discover new biomarkers, i.e., to statistically determine whether a particular analyte not currently identified as a biomarker is actually a whole or part of a particular pathology. This can be accomplished by analyzing data from a statistically relevant number of salivating patients stored in the access log engine 112 who tested positive or negative for the same analyte (e.g., concentration, amount) and had or did not have the same corresponding pathology. This analysis can be supplemented by comparisons with additional data (e.g., lifestyle, genetics, etc.). The saliva analysis engine 106 can have AI learning capabilities to perform such discoveries without being commanded. In some embodiments, this capability is performed by a separate bioinformatics engine. Examples of predictive analysis systems and methods using large datasets are disclosed in U.S. Patent Nos. 7,444,308B2, 9,679,104B2, and 2016 / 0026917A1, which are incorporated herein by reference.

[0090] In some embodiments, health attributes may represent average and / or aggregated values ​​of attributes provided over an extended time period, such as 1-60 days, 1-30 days, 1-5 days, or 6-72 hours. In some embodiments, this is due to the relatively slow and / or discrete saliva sampling rate of the saliva sampling device 102, and the relatively long wearing time of the saliva sampling device 102. The ability to test saliva over an extended period can be a major advantage compared to typical saliva testing protocols that test saliva biomarkers based on the actual time the patient provides a sample at the point of care (i.e., a health snapshot). Embodiments of this disclosure can correlate biomarkers secreted over hours, days, and / or weeks without requiring patient visits to the point of care. It has been proposed that “saliva is a ‘real-time’ fluid because the exocrine glands of the salivary glands produce proteomic profiles that represent the individual’s health and well-being at the time of collection (32). Blood is known to be contained in a closed loop, while saliva is continuously produced and expelled in an open loop… Assessing the entire salivary proteome in a continuous turnover environment is necessary for understanding the physiological and pathological processes associated with oral health and may be crucial for identifying important biomarkers.” Al Muhtaseb, ibid., incorporated by reference.

[0091] Given that such data are rarely accessed outside of controlled clinical settings (such as hospitals), the scientific value of associated health properties based on in vivo samples collected over a longer sampling period can be substantial. For example, single biomarkers previously considered unreliable or unrelated to pathology may have greater predictive weight given the extended sampling period. Therefore, the implementations disclosed herein could potentially be used to provide accurate diagnoses and health predictions while testing fewer types of analytes, i.e., without multiplexing, thus potentially increasing throughput, reducing complexity, and lowering the risk of false positives.

[0092] The health monitoring engine 108 can update the patented health profile and compare recent data with previous health profiles. In some embodiments, the health monitoring engine 108 can provide a statistically weighted status and / or prediction of the patient's health based on the health profile. In some embodiments, alerts can be provided to the patient and / or the patient's caregiver for acute indications so that the patient can seek immediate care. In some embodiments, the patient's health profile can be tracked to provide a lifelong health perspective. Therefore, the collected data can provide a better understanding of the patient's health and disease risks, and can place greater emphasis on disease prevention and maintaining optimal health in the long term. In some embodiments, lifestyle changes, hormones, nutrition, diet, behavior, and / or therapeutic drug therapies can be recommended by the health monitoring engine 108 based on the status predicted by the patient's health profile. In some embodiments, the saliva sampling device 102 can include therapeutic aspects, such as the drug delivery aspect disclosed in International Patent Application No. PCT / US1931635, which is incorporated herein by reference.

[0093] In some embodiments, the health monitoring system 104 includes a gene engine 110. The gene engine 110 can analyze and correlate DNA, RNA, nucleic acids, and / or nucleotides to provide a genetic health profile for storage on a recording engine 112. The genetic profile can be updated based on ongoing research linking genetic information to specific health conditions. The genetic profile can be correlated with health attributes derived from saliva to provide a more tailored and accurate health profile. In some embodiments, genetic ancestry can be provided to a patient based on a saliva test. In some embodiments, genetic information can be provided from a linking system specializing in genetic testing.

[0094] In some embodiments, system 100 includes a saliva testing system 114, which may include hardware and software for processing saliva samples from a saliva sampling device. In some embodiments, the saliva testing system 114 is a point-of-care (POC) system. Examples of saliva-based point-of-care systems are discussed in Yeh, “Current Development of Saliva / Oral Fluid-based Diagnostics.” Tex Dent J. 2010 July; 127(7):651–661, which is incorporated herein by reference.

[0095] In some embodiments, the saliva testing system 114 is configured to test only one type of analyte or one or more types of analytes. Analytes can be extracted from saliva samples using techniques described in: Maniatis, et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor, NY, pp. 280-281 (1982); and Bunyakul and Baeumner, “Combining electrochemical sensors with miniaturized sample preparation for rapid detection in clinical samples.” Sensors (Basel, Switzerland) vol. 15, 1547-64. December 30, 2014, incorporated herein by reference.

[0096] The saliva testing system 114 can be configured to employ one or more testing methods, such as enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR) and / or high-resolution mass spectrometry (HRMS), multiplexing, mass flow cytometry, single-cell genomics, DNA sequencing, RNA sequencing and / or next-generation sequencing. As described in U.S. Patent No. 10,100,356B2, a potentially low-cost POC technology using electric field isolation can also be employed, which discloses a method for magnetically holding beads carrying biological material (e.g., nucleic acids, which may be DNA fragments or amplified DNA in the form of DNA) at specific locations in a matrix, and applying a local electric field to the beads to separate the biological material or products or byproducts of the biological material reaction, which is incorporated herein by reference.

[0097] The recording access device 118 can access all or part of a patient's health profile. In some embodiments, the recording access device 118 is a computing device (e.g., tablet, smartphone, personal computer) belonging to the patient or their caregiver. In some embodiments, the recording access device 118 includes access software with a graphical user interface (GUI) (e.g., cloud application, mobile application) that can be used to access the patient's health profile. In some embodiments, the access software graphically presents certain aspects of the health profile, such as nutritional information, disease information, hormone information, genetic information, hydration information, pH level information, fluoride information, mineralization information, alcohol information, microbiome information, infectious disease information, cancer information, inflammation information, and / or viral information. In some embodiments, the access software communicatively connects to system 100 and can receive unsolicited communications from system 100, such as health alerts and updates.

[0098] Figure 2 A method 200, which can be executed by one or more processors of a system such as system 100 and / or health monitoring system 104, is illustrated. Therefore, method 200 may include... Figure 1 Some or all aspects are not specifically listed. Method 200 can be stored as processor-executable instructions on a processor-readable, non-transitory medium. The processor can be configured to execute method 200.

[0099] In operation 202, data regarding one or more analytes is received. The analytes may be derived from one or more saliva samples collected by a saliva sampling device. Saliva samples may be collected by the saliva sampling device over an extended period of time (e.g., a series of hours, days, or weeks). In some embodiments, the saliva samples may be a collection of several saliva samples collected in a common container over an extended period of time. In some embodiments, the saliva samples may be multiple discretely collected saliva samples collected over an extended period of time, wherein each discretely collected saliva sample corresponds to a specific period of wear of the saliva sampling device.

[0100] In operation 204, one or more analytes from a saliva sample are associated with one or more attributes. Attributes may include nutritional information, disease information, hormonal information, genetic information, hydration information, pH level information, fluoride information, mineralization information, alcohol information, microbiome information, infectious disease information, cancer information, inflammation information and / or viral information, as well as several other attributes discussed herein.

[0101] In operation 206, the patient's health profile is updated to include one or more associated attributes. The health profile can be a statistically based model for different pathologies. The health profile can provide one or more of the following health attributes: state, risk, probability, trend, intensity, level, and quantity. The health profile can be determined using one or more algorithms.

[0102] In some implementations, attributes may represent the average of attributes provided over an extended time period. In some implementations, as part of the update, the health profile may be compared with previous health profile data. In some implementations, as part of the update, statistically weighted health status, recommendations, and / or patient health predictions may be derived from the updated health profile.

[0103] In some implementations, a health profile may include sub-profiles derived from information about associated attributes. Sub-profiles may be statistically based models of a specific pathology. Each sub-profile may be determined by one or more algorithms of method 200. Each sub-profile may provide one or more of the following: state, risk, likelihood, trend, intensity, level, and quantity of a health attribute. Such sub-profiles may include nutritional profiles, disease profiles, hormone profiles, genetic profiles, hydration profiles, pH profiles, fluoride profiles, mineralization profiles, alcohol profiles, microbiome profiles, infectious disease profiles, cancer profiles, inflammation profiles, and / or viral profiles. Each sub-profile may also be derived from data on health events recorded by past diagnostic tests (e.g., blood / serum tests, saliva tests), genetic information, ancestral origin, psychological information, prescription drug use, illicit drug use, alcohol use, smoking history, age, weight, race, environmental exposure history, and family health history.

[0104] In operation 208, it is determined whether the updated health profile triggers an alarm. Alarms may include recommendations and / or information related to one or more of nutrition, disease, hormones, genetics, hydration, pH, fluoride, mineralization, alcohol, microbiome, infectious diseases, cancer, inflammation, and viruses. In some implementations, alarms may be provided to the patient and / or their caregivers for acute or relevant indications (e.g., heart disease, cancer) so that the patient can seek immediate care. Such alarms can be triggered by changes in the health status value of the health profile. If no alarm is triggered, method 200 ends or returns to operation 202.

[0105] In operation 210, if an alarm is triggered, communication can be sent to the access device of the patient and / or the patient's caregiver. In some embodiments, the access device includes access software with a graphical user interface (GUI) (e.g., a cloud application, a mobile application) that can be used to access the patient's health profile. Communication can take the form of electronic communication or application alarms. Furthermore, if the alarm is related to an acute event, a second related alarm can be triggered (e.g., causing a representative to call the hospital, the patient, and / or the patient's caregiver). In some embodiments, the access software graphically presents certain aspects of the health profile, such as nutrition, disease, hormones, genes, hydration, pH, fluoride, mineralization, alcohol, microbiome, infectious diseases, cancer, inflammation, gut health, pregnancy, hydration levels, and viruses. In some embodiments, the access software is a health tracker that provides relative health levels related to certain aspects of the health profile, such as nutrition, disease, hormones, genes, hydration, pH, fluoride, mineralization, alcohol, microbiome, infectious diseases, cancer, inflammation, gut health, pregnancy, hydration levels, and viruses.

[0106] Figure 3A A saliva sampling device 300 according to some embodiments is shown. The saliva sampling device 300 can be constructed similarly to clear aligners or retainers, which are molded for fitting onto the teeth. A series of clear aligners can be used to gradually adjust the position of the teeth from an initial alignment to a final alignment, and retainers are used to maintain the position of the teeth in the final alignment. Clear aligners are typically worn for at least 8-20 hours per day, for a maximum of 9 months. Retainers are typically worn for 6-8 hours each night while the user sleeps.

[0107] Clear aligners are typically made of relatively flexible but elastic polymers, such as polyurethane or polyester, because they require inelastic deformation to move teeth from one position to another. Retainers are generally less flexible because directional forces are no longer required, and therefore retainers can be constructed from thicker polymers and / or more rigid polymers (such as polycarbonate). In some embodiments, the saliva sampling device 300 may be formed from a sheet or sheet polymer material. The saliva sampling device 300 may be fitted to all teeth present in the maxilla or mandible, or to fewer than all teeth.

[0108] In some embodiments, only certain teeth received by the saliva sampling device 300 will be repositioned by the orthodontic appliance, while other teeth may serve as bases or anchoring areas for holding the appliance in place, as it applies force to the teeth to be repositioned. The moved teeth may also serve as bases or anchors for holding the appliance in place while the patient wears it. Typically, no wires or other devices are provided for holding the appliance above the teeth. However, in some cases, it may be necessary or desirable to provide separate anchors on the teeth with corresponding receivers or orifices in the saliva sampling device 300, allowing the appliance to apply selected forces on the teeth. The basic method of determining orthodontic treatment plans using a series of incremental appliances, and the description of molding orthodontic appliances, are described in U.S. Patent Nos. 6,450,807 and 5,975,893, which are incorporated herein by reference.

[0109] Figure 3B A schematic diagram of a saliva sampling device 302 according to some embodiments is shown. The saliva sampling device 302 may be configured structurally similarly to the sampling device 300. The saliva sampling device 302 may include a sample storage section 304, a storage access location 306, one or more sensor modules 308, a communication device 310, and a processing system 312. Many aspects of the saliva sampling device 302 are optional. For example, saliva collection may not require the sensor module 308, the communication device 310, and the processing system 312.

[0110] In some embodiments, aspects of the saliva sampling device 302 are micronized, for example, using microfluidics. Thus, the saliva sampling device 302 can be configured to include structural aspects of a microfluidic device for high-throughput screening. Aspects and examples of microfluidic devices can be found in: U.S. Patent No. 6,508,988, which describes a combinatorial synthesis system that relies on microfluidic flow to control the flow of reagents in a multichannel system; and U.S. Patent No. 5,942,056, which describes a microfluidic assay system for performing high-throughput screening assays, wherein test compounds can flow through multiple channels to simultaneously perform multiple reactions. Further information can be found in: Unger et al., “Monolithic microfabricated valves and pumps by multilayer soft lithography,” 2000, Science 288:113-116; International Application No. WO01 / 01025; International Application No. WO / 02 / 43615; and U.S. Application No. 20030138829. The foregoing publications are incorporated herein by reference.

[0111] In some embodiments, the sample storage portion 304 may be part of a sensor or biosensor, such as a biological receptor. In some embodiments, the sample storage portion 304 includes one or more of a reagent, preservative, detergent, surfactant, lysing agent, or reducing agent. In some embodiments, the sample storage portion 304 may include one or more of a chamber, container, channel, bead, or nanoparticle.

[0112] In some embodiments, the sample storage portion 304 may include an absorbent material (e.g., paper, cloth, fiber, hydrogel, lyophilized hydrogel, synthetic and / or natural superabsorbent polymers (e.g., polysaccharides and proteins, soy protein / poly(acrylic acid) and / or polyacrylate / polyacrylamide copolymers)). In some embodiments, a portion or a separate portion of the absorbent material may be configured to dilute therapeutic substances (e.g., drugs, minerals, vitamins, electrolytes, pH neutralizers) into the oral cavity.

[0113] In some embodiments, synthetic and / or natural superabsorbent polymer composites can be used to avoid problems such as gel blockage. U.S. Application No. 2011 / 0301027A1 discloses an example of a superabsorbent polymer composite comprising a superabsorbent polymer and cellulose fibrils with good flexibility, which is incorporated herein by reference. In some embodiments, superabsorbent polymer sheets can be used, wherein the sample storage portion 304 is in the form of a partial or complete layer. A technique for forming absorbent sheets by extruding an aqueous solution of a superabsorbent polymer as a fiber stream onto a high-speed, hot fiber stream of meltblown fibers of a thermoplastic polymer is disclosed in U.S. Patent No. 5,079,080, the disclosure of which is incorporated herein by reference. A technique for forming superabsorbent paper-like sheets is disclosed in U.S. Patent No. 7,855,315B2, which is incorporated herein by reference.

[0114] In some embodiments, the sample storage portion 304 may be in the form of an absorbent coating on a matrix, such as a superabsorbent polymer coating on a thermoplastic portion of an orthosis or retainer. An example of coating a thermoplastic polymer with a superabsorbent polymer composition is disclosed in U.S. Patent No. 7,812,082B2, which is incorporated herein by reference. An example of a superabsorbent polymer with low water absorption is disclosed in International Publication No. WO2001 / 042339A1 and U.S. Patent No. 6,841,229B2, which are incorporated herein by reference.

[0115] Removal of analytes from superabsorbent polymers can be achieved through a variety of techniques. Superabsorbent polymers have been used as laboratory and forensic tools to extract analytes and fluids of interest. Bang G. et al., “On-Chip Lipid Extraction Using Superabsorbent Polymers for Mass Spectrometry.” Anal. Chem. 2017 Dec 19; 89(24):13365-13373 describes a process for directly dissolving and eluting analytes into an organic solvent, which is incorporated herein by reference. Camarena et al., “An Optimized Centrifugal Method for Separation of Semen from Superabsorbent Polymers for Forensic Analysis” J Forensic Sci, 62:411-416 describes a filtration process for removing semen from superabsorbent polymers used for DNA analysis using a centrifuge, which is incorporated herein by reference.

[0116] In some embodiments, the sample storage portion 304 and / or the channels connected thereto may be absorbent materials wholly or partially coated with a hydrophobic material to slow absorption to a desired rate or prevent absorption until desired. In some embodiments, the hydrophobic material is configured to break or fracture over time or by applied force, for example, in the case of a discrete sample storage portion 304, where manual force applied by a patient to a portion of the saliva sampling device 302 (e.g., squeezing between fingers) can prepare the affected sample storage portion 304 for saliva absorption.

[0117] In some embodiments, the connection channel to the sample storage portion 304 can be partially or completely blocked with a hydrophilic material configured to break or fracture over time or by applied force, such as by the patient manually applying force to the blocked channel. Because the channel-blocking material is hydrophilic, it can still absorb saliva even after almost complete blockage following fracture. In some embodiments, the sample storage portion 304 can be a relatively high-quality absorbent material, such that complete or desired saliva absorption is achieved through contact with saliva after an extended period of time (e.g., 1 hour, several hours, several days, or several weeks). In some embodiments, the relatively high-quality absorbent material can be adjusted using a relatively small saliva feeding channel.

[0118] One or more storage access locations 306 provide access from the oral cavity to one or more sample storage portions 304. In some embodiments, the storage access location 306 may be an opening in a portion of a saliva sampling device 302. In some embodiments, the storage access location 306 may be multiple openings. In some embodiments, the storage access location 306 may be a size that restricts saliva intake. In some embodiments, the storage access location 306 may be one or more microfluidic openings. In some embodiments, the storage access location 306 may be covered with a user-removable cap that the user can move to enable sampling at different time periods. In some embodiments, the storage access location 306 may be covered with a bioabsorbable cap. In some embodiments, to provide saliva samples at different time periods, multiple bioabsorbable caps may cover multiple discrete storage access locations 306 and have different thicknesses or properties, such that the caps are eroded / absorbed at different points during use, e.g., 1 hour, 12 hours, 48 ​​hours, etc. In some implementations, one or more storage access locations 306 may be located on the saliva sampling device 302 to be positioned closest to one of the parotid gland, submandibular gland, and sublingual gland when worn in the mouth.

[0119] Storage access location 306 may be in fluid communication with sample storage portion 304. In some embodiments, a microfluidic pump is in fluid communication with both storage access location 306 and sample storage portion 304 and is configured to move saliva from storage access location 306 to sample storage portion 304. In some embodiments, the fluid path between storage access location 306 and sample storage portion 304 is configured to move saliva from storage access location 306 to sample storage portion 304 using capillary action. In some embodiments, the fluid path includes a wicking composition, such as cellulose, cloth, hydrophilic material / coating, and / or hydrogel, to wick saliva from storage access location 306 to sample storage portion 304.

[0120] Sensor module 308 can be configured to react with, stop, or induce signal propagation in response to a specific analyte. Sensor module 308 may include a transducer coupled to a bioreactor reacting with the specific analyte. The reaction may cause the transducer to generate an electrical effect, such as a voltage and / or current signal. Sensor module 308 may include a signal processor configured to receive the electrical effect from the transducer and output a result, such as generating one or more digital signals to indicate the presence of the analyte in the bioreactor. Sensor module 308 may provide status indications to processing system 312 continuously or intermittently.

[0121] In some embodiments, sensor module 308 may be a screen-printed circuit directly printed onto the substrate of saliva sampling device 302 or onto a separate substrate. Examples of screen-printed biosensors are disclosed in Alonso-Lomillo MA et al., “Screen-printed biosensors in microbiology; A review.” Talanta 2010; 82:1629–1636, which is incorporated herein by reference. Further examples of saliva-based biosensors that can be used for sensor module 308 can be found in Radha SPMalon et al., “Saliva-Based Biosensors: Noninvasive Monitoring Tool for Clinical Diagnostics,” BioMed Research International, vol. 2014, document ID 962903, 2014, which is also incorporated herein by reference. Ballesta Claver, J., “Disposable electrochemiluminescent biosensor for lactate determination in saliva.” Analyst 2009, 134, 1423-1432, discusses an example of an electrochemiluminescent saliva-based lactate biosensor, which is incorporated herein by reference.

[0122] The communication device 310 can electrically communicate with the sensor module 308 and / or the processing system 312 and can be configured to transmit data in response to the sensor's output. The data can replicate the digital output of the sensor module 2018 or provide a processed, or in some embodiments, simplified, signal. The communication device 310 can wirelessly transmit data to an external device for a predetermined time period or upon prompting. Such external devices may include a dedicated wireless receiver, a remote server, a smart wearable device, a smartphone, a smart home device, and / or a tablet. In some embodiments, this may be via a network connection through a router or other forms of direct communication, such as... Bluetooth or WiFi Perform communication.

[0123] Saliva sampling device 302 may include one or more processors, such as a low-level processor for handling relatively simple tasks (e.g., sensor monitoring) and a high-level processor for handling more complex tasks (e.g., data management and communication). These processors may communicate with each other and with other components of saliva sampling device 302 to function as processing system 312. In some embodiments, the low-level processor may operate independently of the high-level processor. Processing system 312 may be configured to analyze the amount of time a condition is detected by sensor module 308. Processing system 110 may create a record of the amount of time a condition is detected by sensor module 120. Examples of processing and wireless communication systems on oral devices are disclosed in Kim et al., “Wearable salivary uric acid mouthguard biosensor with integrated wireless electronics.” Biosensors & bioelectronics vol. 74 (2015): 1061-8, which is incorporated herein by reference.

[0124] The saliva sampling device 302 may include a battery-based power source and / or a line power source. In some embodiments, the line power source may be used to charge the battery-based power source. The line power source may represent a port (e.g., a USB port) and a removable wired connection (e.g., a USB cable) and / or an inductive charging module that receives DC power from an external power source (e.g., an AC / DC wall plug, a USB port). In some embodiments, the line power source is provided wirelessly (e.g., Wi-Fi, Bluetooth).

[0125] Figure 4A An exploded view of a material stack 400 that can be formed (e.g., thermoformed) into a saliva sampling device according to some embodiments is shown. The material stack 400 may include a base layer 402, a sampling layer 404, and a top layer 406. In some embodiments, the layers are separated prior to forming the saliva sampling device. In some embodiments, two or all layers are permanently attached (e.g., bonded, co-extruded) to form a single composite layer prior to forming the saliva sampling device. The base layer 402 and the top layer 406 may be thermoformable polymer materials, and each may have a single layer or multiple layers.

[0126] Material laminates 400 formed from thermoformable polymer materials may be advantageous because they allow for the use of known and readily available orthodontic and retainer forming methods, and therefore can be produced at the point of care. Figure 4B The diagram shows an exploded view of each of the base layer 402, sampling layer 404, and top layer 406, after trimming excess material from each formed layer. It should be understood that the construction of the saliva sampling device is not limited to thermoforming and can also utilize other technologies (e.g., 3D printing, casting).

[0127] In some embodiments, the thickness of these layers can be in the range of 0.001-0.035 inches, and can be constructed from polyester, copolyester, polycarbonate, thermoplastic polyurethane, polypropylene, polyethylene, polypropylene and polyethylene copolymer, acrylic acid, cyclic block copolymer, polyetheretherketone, polyamide, polyethylene terephthalate, polybutylene terephthalate, polyetherimide, polyethersulfone, polypropylene terephthalate, or combinations thereof.

[0128] In some embodiments, one or both of the base layer 402 and the top layer 406 may include an opening (e.g., storage access location 306) for providing fluid communication with the sampling layer 404. Such an opening may be microfluidic in nature and / or uniformly or non-uniformly located on the layer. In some embodiments, the base layer 402 and the top layer 406 do not include openings, and the fluid path to the sampling layer 404 begins at the edges of the base layer 402 and the top layer 406, which may connect or nearly connect at discrete points, in addition to one or more discrete openings for fluid passage.

[0129] Sampling layer 404 may include one or more sampling aspects disclosed herein, as described with reference to saliva sampling devices 102 and 300. In some embodiments, sampling layer 404 includes a thermoplastic material as a base matrix for carrying additional aspects. For example, in some embodiments, sampling layer 404 may include one or more of the following: microfluidic circuitry, channels, chambers, screen-printed aspects, screen-printed circuitry, sample storage portions, communication devices, power supplies, sensors, biosensors, and / or absorbent portions of a matrix attached or formed (e.g., by photolithography, etching, printing, and / or bonding).

[0130] In some embodiments, sampling layer 404 does not include a thermoplastic material as a base matrix for supporting additional aspects. For example, sampling layer 404 may be constructed of highly flexible materials such as silicone, fabric, cellulose, and / or composite materials. In some embodiments, sampling layer 404 may be incorporated into one or both of base layer 402 and top layer 406. In some embodiments, base layer 402 and top layer 406 may include sampling layer 400 by being joined at the outer edges of base layer 402 and top layer 406.

[0131] It should be understood that aspects of the material stack 400 are optional or limiting. For example, in some embodiments, one or both of the base layer 402 and the top layer 406 are not required. In some embodiments, additional polymers and / or sampling layers may be used. In some embodiments, the sampling layer 404 is the only layer required to form the material stack 400 into a saliva sampling device. Furthermore, although the sampling layer 404 is depicted as being dimensionally continuous with the base layer 402 and the top layer 406, such dimensional designation is not required.

[0132] In some implementations, the sampling layer 404 is discontinuous relative to the additional layer. An example of this is as follows: Figure 4C As shown, a material stack 408 is illustrated. Material stack 408 shares many of the same aspects and options as material stack 400, which will not be repeated here for brevity. Material stack 408 includes a base layer 410, storage portions 412a-c, and a top layer 414, the top layer 414 including storage access locations 416a-c. As shown, the storage portions 412a-c are discrete from each other, and each has a corresponding storage access location 416a-c for fluid communication with the oral cavity. Storage access locations 416a-c may include openings (e.g., microfluidic-sized openings) for providing fluid communication from the oral cavity to the storage access location 416a-c.

[0133] Storage portions 412a-c may have the same aspects as described with respect to sampling layer 404; however, storage portions 412a-c need not be identical, and each may have different aspects (e.g., biosensors, circuitry, absorption quality, etc.). Similarly, storage access locations 416a-c need not be identical, and each may have different aspects (e.g., the number and / or size of openings).

[0134] In some embodiments, storage access locations 416a-c may be covered by user-removable caps that the user can move to sample at different time periods. In some embodiments, to provide saliva samples at different time periods, multiple bioabsorbable caps may cover multiple discrete storage access locations 416a-c and have different thicknesses and / or properties, causing the caps to corrode / absorb at different time points during use, such as 1 hour, 12 hours, 48 ​​hours, etc. In some embodiments, one or more storage access locations 416a-c may be positioned to be closest to one of the parotid, submandibular, and sublingual glands when worn in the oral cavity. In some embodiments, storage access locations are not included on the top layer 414 but on the bottom layer 410. In some embodiments, storage access locations are included only on the bottom layer 410. In some embodiments, neither the bottom layer 410 nor the top layer 414 includes storage access locations, and fluid communication to storage portions 412a-c occurs at the edges of the bottom layer 410 and the top layer 414.

[0135] Figure 5 An example of a basic process 500 for forming an orthodontic appliance is depicted. As shown, material 502 can form a portion of a saliva sampling device 500, which in some embodiments can also serve as an orthodontic appliance or retainer. Material 502 can be a single layer to form a single or unique shell of the saliva sampling device 500, or multiple layers of non-fixed material to form multiple shells at once. In some embodiments, material 502 can be one or more layers of material stacks 400 and 408. In this example process, the saliva sampling device 500 can be produced using a physical dental model or mold 504. The saliva sampling device 500 can be produced by heating material 502 and then vacuum or pressure molding the material onto the teeth of the physical dental model 504. The saliva sampling device 500 is a direct representation of the physical dental model.

[0136] Once formed, the layers can be secured to each other according to the patient's desired working flexibility. Securing methods include chemical bonding, localized melting, fasteners, and / or localized physical deformation to bond the shell together. Before or after securing, excess material on the sheets can be trimmed to form the final tooth positioning appliance, which can be used for the patient's orthodontic treatment. Some or all edges of each layer can be sealed with a flexible material such as silicone to prevent liquid intrusion.

[0137] refer to Figure 6 An embodiment of a dedicated computer system 1100 is illustrated. For example, one or more intelligent components, processing system 110, and components thereof may be a dedicated computer system 1100. Such a dedicated computer system 1100 may be partially or wholly integrated as a saliva sampling device and / or any other computerized device discussed herein, such as a remote server, mobile device, or network. The above-described methods may be implemented by a computer program product that directs the computer system to perform the actions of the methods and components described above. Each such computer program product may include a set of instructions (code) contained on a computer-readable medium that directs the processor of the computer system to perform corresponding actions. The instructions may be configured to run sequentially, or in parallel (e.g., under different processing threads), or in combination thereof. After the computer program product is loaded onto a general-purpose computer system 1126, it is converted into a dedicated computer system 1100.

[0138] A dedicated computer system 1100 includes a computer 1102, a monitor 1106 connected to the computer 1102, one or more optional additional user output devices 1130 connected to the computer 1102, one or more user input devices 1140 (e.g., keyboard, mouse, ball, touchscreen) connected to the computer 1102, an optional communication interface 1150 connected to the computer 1102, and a computer program product 1105 stored in tangible computer-readable storage within the computer 1102. The computer program product 1105 instructs the computer system 1100 to perform the methods described above. The computer 1102 may include one or more processors 1160 that communicate with a plurality of peripheral devices via a bus subsystem 1190. These peripheral devices may include user output devices 1130, user input devices 1140, communication interface 1150, and a storage subsystem, such as random access memory (RAM) 1170 and non-volatile storage drives 1180 (e.g., disk drives, optical drives, solid-state drives), which are in the form of tangible computer-readable storage.

[0139] Computer program product 1105 may be stored on non-volatile storage drive 1180 or another computer-readable medium accessible to computer 1102 and loaded into random access memory (RAM) 1170. Each processor 1160 may include a microprocessor, such as from Or Advanced Micro Devices, Microprocessors, etc. To support computer program product 1105, computer 1102 runs an operating system that handles communication between computer program product 1105 and the aforementioned components, as well as communication between the aforementioned components supporting computer program product 1105. Exemplary operating systems include those from Microsoft Corporation. etc., from Sun Microsystems LINUX, UNIX, etc.

[0140] User input device 1140 includes all possible types of means and mechanisms for inputting information into computer 1102. These may include a keyboard, keypad, mouse, scanner, digital drawing tablet, touchscreen integrated into the display, audio input devices such as a voice recognition system, microphone, and other types of input devices. In various embodiments, user input device 1140 is typically embodied as a computer mouse, touchscreen, wireless remote control, drawing tablet, or voice command system. User input device 1140 typically allows a user to select objects, icons, text, etc., appearing on monitor 1106 via commands such as clicking buttons. User output device 1130 includes all possible types of means and mechanisms for outputting information from computer 1102. These may include a display (e.g., monitor 1106), printer, non-visual displays such as audio output devices, etc.

[0141] Communication interface 1150 provides an interface to other communication networks (such as communication network 1195) and devices, and can be used as an interface for receiving data from and transmitting data to other systems, WANs, and / or the Internet. Implementations of communication interface 1150 typically include Ethernet cards, modems (telephone, satellite, cable, ISDN), (asynchronous) digital subscriber line (DSL) units, etc. interface, Interfaces, wireless network adapters, etc. For example, communication interface 1150 can be connected to a computer network, Bus, etc. In other embodiments, the communication interface 1150 may be physically integrated on the motherboard of the computer 1102, and / or may be software programs, etc.

[0142] RAM 1170 and non-volatile memory drive 1180 are examples of tangible computer-readable media configured to store data as described in embodiments of the computer program product of the present invention, including executable computer code, human-readable code, etc. Other types of tangible computer-readable media include floppy disks, removable hard disks, optical storage media (such as CD-ROMs, DVDs, barcodes), semiconductor memories (such as flash memory), read-only memory (ROM), battery-supported volatile memory, network storage devices, etc. RAM 1170 and non-volatile memory drive 1180 can be configured to store basic programming and data structures that provide functionality for various embodiments of the present invention, as described above.

[0143] The software instruction set providing the functionality of this invention can be stored in RAM 1170 and non-volatile memory drive 1180. These instruction sets or code can be executed by processor 1160. RAM 1170 and non-volatile memory drive 1180 may also provide a repository for storing data and data structures used according to this invention. RAM 1170 and non-volatile memory drive 1180 may include multiple memories, including main random access memory (RAM) for storing instructions and data during program execution and read-only memory (ROM) for storing fixed instructions. RAM 1170 and non-volatile memory drive 1180 may include a file storage subsystem providing persistent (non-volatile) storage of program and / or data files. RAM 1170 and non-volatile memory drive 1180 may also include a removable storage system, such as removable flash memory.

[0144] Bus subsystem 1190 provides a mechanism that allows various components and subsystems of computer 1102 to communicate with each other as intended. Although bus subsystem 1190 is schematically shown as a single bus, alternative implementations of the bus subsystem may utilize multiple buses or communication paths within computer 1102.

[0145] Throughout the foregoing description, and for purposes of explanation, numerous specific details have been set forth to provide a thorough understanding of the described techniques. However, it will be apparent to those skilled in the art that these techniques can be practiced without some of these specific details. Although various embodiments incorporating these teachings have been shown and described in detail, those skilled in the art can readily devise many other variations of embodiments or mechanisms to incorporate these techniques. Furthermore, embodiments may include various operations as described above, fewer operations, or more operations; or sequential operations. Therefore, the scope and spirit of the invention should be determined based on the appended claims and their legal equivalents.

Claims

1. A health monitoring system, comprising: One or more processors; A memory connected to the one or more processors, the memory containing instructions that, when executed by the one or more processors, cause the one or more processors to: Receive data from at least one analyte from at least one saliva sample, said saliva sample being collected by a saliva sampling device configured to be worn in a patient's mouth, said saliva sampling device comprising one of: a polymer retainer and a polymer orthodontic appliance; The at least one analyte of the at least one saliva sample is associated with at least one health attribute, wherein, during the patient's incremental wearing of the saliva sampling device, the at least one saliva sample is collected by the saliva sampling device over multiple days, wherein the at least one saliva sample is collected by the saliva sampling device in one or more time periods, the one or more time periods being initiated by user operation of the saliva sampling device capable of collecting saliva, wherein the user operation includes removing a cap located at a storage access location on the saliva sampling device; and updating the patient's health profile based on the at least one health attribute.

2. The system according to claim 1, wherein, The health profile includes at least one profile of at least one health condition, and wherein the at least one health attribute is used to update at least one health condition profile.

3. The system according to claim 1, wherein, The health profile includes at least one risk profile for at least one disease, and wherein the at least one associated attribute is used to update the at least one risk profile.

4. The system according to claim 1, wherein, The health profile includes at least one nutritional profile in at least one nutritional aspect, and the at least one health attribute is used to update the at least one nutritional profile.

5. The system according to claim 1, wherein, Each incremental wearing period is at least one hour.

6. The system according to claim 1, wherein, The at least one saliva sample is one of a plurality of saliva samples collected by the saliva sampling device over several days.

7. The system according to claim 1, wherein, Processing at least one of the health attributes to provide one or more of the following: nutritional information, disease information, hormone information, and genetic information.

8. The system according to claim 7, wherein, The nutritional information includes one or more of the following: hydration information, pH information, fluoride information, mineralization information, alcohol information, and microbiome information.

9. The system according to claim 7, wherein, The disease information includes one or more of the following: infectious disease information, cancer information, inflammation information, and virus information.

10. The system according to claim 1, wherein, The at least one analyte includes at least one biomarker from the at least one saliva sample.

11. The system of claim 1, wherein the executed instructions further cause the one or more processors to associate at least one analyte of at least one saliva sample with at least one genetic property.

12. The system of claim 1, wherein the executed instructions further cause the one or more processors to store the health profile.

13. The system of claim 1, wherein the executed instructions further cause the one or more processors to provide health monitoring updates and / or alarms to at least one access device.

14. The system according to claim 1, wherein, The saliva sampling device is one of a plurality of saliva sampling devices, and the health profile is updated and maintained based on a plurality of associated health attributes derived from a plurality of saliva samples collected by the plurality of saliva sampling devices.

15. The system according to claim 1, wherein, The saliva sampling device includes at least one biosensor.

16. The system according to claim 1, wherein, The saliva sampling device includes at least one communication device configured to wirelessly connect to a network and / or a network access device, wherein the saliva sampling device wirelessly transmits data to the one or more processors, the data being indicative of or not indicative of the at least one analyte.

17. The system of claim 1, wherein the user operation includes the user removing a cover from the saliva sampling device for storing an access location, and wherein the storage access location includes an opening that is a portion of the saliva sampling device.

18. The system of claim 1, wherein the saliva sampling device includes a plurality of saliva storage sections configured to store the at least one saliva sample over a plurality of days; and each of the plurality of saliva storage sections is configured to be activated by a user via a user operation, the user operation including removing a cover on the saliva sampling device to access a storage location.

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