Methods and systems for secure patient data handling

Abstract

The present disclosure provides a system for secure patient data handling. The system comprises an instrument configured to test patient samples from a plurality of patients thereby producing test data, wherein no health record information or patient unique identifying information of any of the plurality of patients is received, stored, or accessed at or by the instrument.

Description

Attorney Docket No. 61070-708601METHODS AND SYSTEMS FOR SECURE PATIENT DATA HANDLINGCROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 721,938, filed November 18, 2024, which application is incorporated herein by reference.BACKGROUND

[0002] Traditional laboratory testing typically involves multiple steps that take a significant amount of time. These multiple steps may comprise collecting samples from a patient at the patient care location, transporting the samples to a centralized laboratory or testing location, subjecting the samples to processing steps, and then returning the result to the patient. There is a need for point-of-care testing that processes tests and returns test results to the patient immediately.SUMMARY

[0003] In an aspect, the present disclosure provides a system for secure patient data handling. In some embodiments, the system comprises an instrument configured to test patient samples from a plurality of patients thereby producing test data. In some cases, no health record information or patient unique identifying information of any of the plurality of patients is received, stored, or accessed at or by the instrument. In some embodiments, the system further comprises an operating device configured to be used with the instrument. In some cases, the operating device comprises software for operating the instrument. In some cases, the operating device is configured to receive the test data from the instrument but does not receive, store, or access the health record information of any of the plurality of patients. In some cases, the operating device is further configured to interact with the instrument, a first cloud environment, and a second cloud environment. In some cases, the first cloud environment is configured to store the health record information of the plurality of patients. In some cases, the second cloud environment is configured to receive the test data from the operating device and process the test data thereby generating processed test data. In some cases, the second cloud environment is further configured to send the processed test data to the first cloud environment, thereby linking the processed test data of each of the plurality of patients with the health record information of each of the plurality of patients. In some embodiments, the instrument is configured to be used at a clinical testing or point-of-care location to test the patient samples. In some embodiments, the first cloud environment isAttorney Docket No. 61070-708601configured to prevent unauthorized access to the health record information of any of the plurality of patients using one or more network security measures. In some embodiments, the one or more network security measures comprises a firewall. In some embodiments, the software for operating the instrument is configured to facilitate communications between the instrument and each of the first and second cloud environments. In some embodiments, the software for operating the instrument is configured to interact with the first cloud environment to link the health record information of a select patient with the test data of the select patient produced by the instrument. In some embodiments, the software for operating the instrument is configured to receive patient unique identifying information to identify a select patient and link the select patient with the select patient’s health record information stored in the first cloud environment. In some embodiments, the software for operating the instrument is configured to delete the patient unique identifying information after the patient unique identifying information has been received for a time duration. In some embodiments, the time duration ranges from about 12 hours to about 48 hours. In some embodiments, the software for operating the instrument is not configured to access the patient unique identifying information. In some embodiments, the software for operating the instrument is walled off from accessing the patient unique identifying information. In some embodiments, the software for operating the instrument is configured to receive an encounter identification key to identify a select patient and link the select patient with the select patient’s health record information stored in the first cloud environment. In some embodiments, the patient unique identifying information, the health record information, and the test data are all stored separately in the system. In some embodiments, the operating device comprises a tablet, a laptop computer, or any other type of computing device. In some embodiments, the operating device is configured to be operated by an operator using a graphical user interface in the software to run a test on the instrument. In some embodiments, an operator identity (ID) information is assigned to the operator. In some embodiments, the operator ID information is stored in the first cloud environment. In some embodiments, the operator ID information is verified when the operator starts the test on the instrument. In some embodiments, the first cloud environment is configured to interface with an electronic health record (EHR) system. In some embodiments, the health record information of the plurality of patients is stored in the EHR system. In some embodiments, the first cloud environment is operably connected to the EHR system via a Health Level 7 (HL7) or Fast Healthcare Interoperability Resources (FHIR)-based application programming interface (API). In some embodiments, the first cloud environment and the EHR system are used to coordinate clinical workflows. In someAttorney Docket No. 61070-708601embodiments, the first cloud environment and the EHR system are used for patient services which include tracking of the plurality of patients in the EHR system based on identities of the plurality of patients. In some embodiments, the first cloud environment and the EHR system are used for encounter services which include locating active encounters based on the identities of the plurality of patients. In some embodiments, the first cloud environment and the EHR system are used for personnel services which include locating and storing the operator ID information. In some embodiments, the first cloud environment is in communication with a government agency healthcare data monitoring portal. In some embodiments, the health record information of the plurality of patients is transmitted with the processed test data from the first cloud environment to the government agency healthcare data monitoring portal for patient population tracking. In some embodiments, the instrument is selected from the group consisting of a polymerase chain reaction (PCR) instrument, an imaging instrument, and an instrument configured to detect one or more biomarkers in the patient samples. In some embodiments, the instrument is the polymerase chain reaction (PCR) instrument. In some embodiments, the PCR instrument comprises a base station and one or more operating modules. In some embodiments, the PCR instrument is a rapid PCR instrument. In some embodiments, the instrument is the imaging instrument. In some embodiments, the patient samples comprise imaging samples selected from the group consisting of a magnetic resonance imaging (MRI) scan, a computed tomography (CT) scan, a positron emission tomography (PET) scan, and an ultrasound scan. In some embodiments, the instrument is the instrument configured to detect one or more biomarkers in the patient samples. In some embodiments, the instrument configured to detect the one or more biomarkers in the patient samples comprises an albumin analyzer, a blood lactate analyzer, a cardiac marker analyzer, a clinical chemistry analyzer, a coagulation analyzer, a creatinine analyzer, a C-reactive protein analyzer, or a blood glucose analyzer. In some embodiments, the patient samples are selected from the group consisting of a blood sample, a lacrimal fluid sample, a saliva sample, a mucus sample, a sputum sample, a feces sample, a cerebrospinal fluid sample, and a urine sample. In some embodiments, a patient sample is collected in a different location from a location of the instrument. In some embodiments, the second cloud environment is further configured to store and use barcode information, instrument telemetry data, log files, algorithms or any combination thereof for data processing. In some embodiments, the second cloud environment is configured to process the test data by executing the algorithms on the test data thereby producing processed test data. In some embodiments, the test data comprises PCR test data. In some embodiments, the algorithmsAttorney Docket No. 61070-708601are used to determine cycle threshold values and interpret the cycle threshold values to process the PCR test data thereby producing processed PCR test data. In some embodiments, the second cloud environment is configured to process the instrument telemetry data and log files to enable monitoring and proactive servicing of the instrument, using at least in part failure mode models, component wear and tear monitoring and predictions, or over-the-air updates to extend component life of the instrument, or any combination thereof. In some embodiments, the second cloud environment is configured to transmit software or firmware updates to the instrument or to the software for operating the instrument. In some embodiments, the software for operating the instrument is further configured to store the test data. In some embodiments, the test data is stored on the software for operating the instrument for up to a number of test runs, wherein the number of test runs ranges from about 50 to about 1000. In some embodiments, each of the first cloud environment or the second cloud environment comprises one or more servers. In some embodiments, the first cloud environment and the second cloud environment are segregated from each other. In some embodiments, the first cloud environment and the second cloud environment are compartmentalized within an integrated cloud environment. In some embodiments, the system further comprises a third cloud environment, wherein the third cloud environment comprises manufacturing information for single-use test components used in the instrument, instrument manufacturing information, or any combination thereof. In some embodiments, the manufacturing information for the single-use test components or the instrument manufacturing information is provided to the software for operating the instrument to track a manufacturing or recall status of the single-use test components or the instrument. In some embodiments, the single-use test components comprise single-use discs used in a PCR instrument. In some embodiments, a status of a single-use disc used in the PCR instrument is validated prior to performing a test on the PCR instrument by linking the single-use disc with a manufacturing or recall status of the single-use disc stored in the third cloud environment.

[0004] In an aspect, the present disclosure provides a method for secure patient data handling. In some embodiments, the method comprises providing an instrument to test patient samples from a plurality of patients thereby producing test data. In some cases, no health record information or patient unique identifying information of any of the plurality of patients is received, stored, or accessed at or by the instrument. In some embodiments, the method further comprises using an operating device with the instrument. In some cases, the operating device comprises software for operating the instrument. In some cases, the operating device is used to receive the test data from the instrument but not receive, store, or access the healthAttorney Docket No. 61070-708601record information of any of the plurality of patients. In some cases, the operating device is further used to interact with the instrument, a first cloud environment, and a second cloud environment. In some embodiments, the method further comprises using the first cloud environment to store the health record information of the plurality of patients. In some embodiments, the method further comprises using the second cloud environment to receive the test data from the operating device and process the test data thereby generating processed test data. In some embodiments, the method further comprises sending the processed test data from the second cloud environment to the first cloud environment, thereby linking the processed test data of each of the plurality of patients with the health record information of each of the plurality of patients.

[0005] In an aspect, the present disclosure provides a method of using an instrument to test patient samples, the method comprising: receiving one or more test samples by the instrument; using the instrument to obtain or collect test data from the one or more test samples; and producing one or more test results by the instrument. In some cases, the instrument receives the one or more test samples from a plurality of patients. In some cases, no health record information of the plurality of patients is received, stored, or accessed at or by the instrument.

[0006] Another aspect of the present disclosure provides a system comprising one or more computer processors and computer memory coupled thereto. The computer memory comprises machine executable code that, upon execution by the one or more computer processors, implements any of the methods above or elsewhere herein.

[0007] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.INCORPORATION BY REFERENCE

[0008] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated byAttorney Docket No. 61070-708601reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material.BRIEF DESCRIPTION OF THE DRAWINGS

[0009] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “Figure” and “FIG.” herein), of which:

[0010] FIG. 1 illustrates a line drawing of a top view of a rotatable disc described herein in the context of an analytical device described herein.

[0011] FIG.2 illustrates a top view of a rotatable disc described herein.

[0012] FIGs. 3A-3C illustrate multiple views of a rotatable disc described herein. FIG.3A illustrates two components used to manufacture some embodiments of a rotatable disc described herein. FIG.3B illustrates a close-up example of a reaction chamber comprised on a rotatable disc described herein. FIG.3C illustrates an additional view of a manufactured rotatable disc comprising a plurality of reaction chambers designed for RT-PCR.

[0013] FIG. 4 illustrates the components used to manufacture some embodiments of a rotatable disc described herein.

[0014] FIG. 5 illustrates a line drawing overview of an analytical device for processing a target nucleic acid.

[0015] FIGs. 6A-6B illustrate a cartoon schematic of an analytical device for processing a target nucleic acid. FIG. 6A illustrates a front view of the analytical device. FIG. 6B illustrates a side view of the analytical device.

[0016] FIGs. 7A-7D illustrate a cartoon schematic of an analytical device for processing a target nucleic acid showing a heat sealer element for sealing a channel on a rotatable disc. FIG. 7A illustrates an overview of the heat sealer housed within an analytical above the channel on the rotatable disc. FIG. 7B illustrators a close view of the heat sealer housed within an analytical above the channel on the rotatable disc. FIG. 7C illustrates an overview of the heat sealer housed within an analytical device contact with the channel on the rotatable disc. FIG. 7D illustrators a close view of the heat sealer housed within an analytical device contact with the channel on the rotatable disc.

[0017] FIG. 8 shows a schematic of a point-of-care PCR device integrated with the cloud system described herein.Attorney Docket No. 61070-708601

[0018] FIG. 9 illustrates a workflow for a cloud system integrated with a point-of-care PCR device.

[0019] FIG. 10 shows different types of data in the cloud system and how they are sent to different parts of the system.

[0020] FIG. 11 illustrates a workflow for a cloud system integrated with a point-of-care PCR device.

[0021] FIG. 12 shows a diagram of interactions between the manufacturing cloud, the engineering cloud, and the protected information cloud.

[0022] FIG. 13 shows interactions between the PCR device, a PCR disc, and the manufacturing cloud.

[0023] FIG. 14 shows data communicated with the engineering cloud in a PCR device system.

[0024] FIG. 15 shows that instrument telemetry in a PCR device system can be tracked for proactive service.

[0025] FIG. 16 shows a PCR system’s interaction with a protected information cloud.

[0026] FIG. 17 shows a computer system that is programmed or otherwise configured to implement methods provided herein.

[0027] FIG. 18 shows a view of an embodiment of an operator application as described herein.

[0028] FIG. 19 shows a view of an embodiment of an operator application as described herein.

[0029] FIG. 20 shows a view of an embodiment of an operator application as described herein.

[0030] FIG. 21 shows a view of an embodiment of an operator application as described herein.

[0031] FIG. 22 shows a view of an embodiment of an operator application as described herein.

[0032] FIG. 23 shows a view of an embodiment of an operator application as described herein.

[0033] FIG. 24 shows a view of an embodiment of an operator application as described herein.

[0034] FIG. 25 shows a view of an embodiment of an operator application as described herein.Attorney Docket No. 61070-708601

[0035] FIG. 26 shows a view of an embodiment of an operator application as described herein.

[0036] FIG. 27 shows a view of an embodiment of an operator application as described herein.

[0037] FIG. 28 shows a view of an embodiment of an operator application as described herein.DETAILED DESCRIPTION

[0038] While various embodiments of the invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed.

[0039] Whenever the term “at least,” “greater than,” or “greater than or equal to” precedes the first numerical value in a series of two or more numerical values, the term “at least,” “greater than” or “greater than or equal to” applies to each of the numerical values in that series of numerical values. For example, greater than or equal to 1, 2, or 3 is equivalent to greater than or equal to 1, greater than or equal to 2, or greater than or equal to 3.

[0040] Whenever the term “no more than,” “less than,” or “less than or equal to” precedes the first numerical value in a series of two or more numerical values, the term “no more than,” “less than,” or “less than or equal to” applies to each of the numerical values in that series of numerical values. For example, less than or equal to 3, 2, or 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1.

[0041] Certain inventive embodiments herein contemplate numerical ranges. When ranges are present, the ranges include the range endpoints. Additionally, every sub range and value within the range is present as if explicitly written out. The term “about” or “approximately” may mean within an acceptable error range for the particular value, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, “about” may mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively, “about” may mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Where particular values are described in the application and claims, unless otherwise stated the term “about” meaning within an acceptable error range for the particular value may be assumed.DefinitionsAttorney Docket No. 61070-708601

[0042] Unless defined otherwise, all terms of art, notations and other technical and scientific terms or terminology used herein are intended to have the same meaning as is commonly understood by one of ordinary skill in the art to which the claimed subject matter pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and / or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art.

[0043] Throughout this application, various embodiments may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0044] As used in the specification and claims, the singular forms “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a sample” includes a plurality of samples, including mixtures thereof.

[0045] The terms “determining,” “measuring,” “evaluating,” “assessing,” “assaying,” and “analyzing” are often used interchangeably herein to refer to forms of measurement. The terms include determining if an element is present or not (for example, detection). These terms can include quantitative, qualitative or quantitative and qualitative determinations. Assessing can be relative or absolute. “Detecting the presence of’ can include determining the amount of something present in addition to determining whether it is present or absent depending on the context.

[0046] The terms “subject,” “individual,” or “patient” are often used interchangeably herein. A “subject” can be a biological entity containing genetic material. The biological entity can be a plant, animal, or microorganism, including, for example, bacteria, viruses, fungi, and protozoa. The subject can be tissues, cells, or fragments thereof, derived from a biological entity obtained in vivo or cultured in vitro. The subject can be a mammal, for example, a human. The subject may be diagnosed or suspected of being at high risk for a disease. In some cases, the subject is not necessarily diagnosed or suspected of being at high risk for the disease.Attorney Docket No. 61070-708601

[0047] As used herein, the term “about” a number refers to that number plus or minus 10% of that number. The term “about” a range refers to that range minus 10% of its lowest value and plus 10% of its greatest value.

[0048] As used herein, the term “molecular amplification” refers to assay or method or test used to detect nucleic acids in sample. This can be used in, for example, experimental research, clinical medicine development, infectious diagnosis, gene cloning, and industrial quality control. Molecular amplification can also be used as part of a diagnostic test. The term “molecular amplification” referred herein intends to cover all methods that are designed to amplify (e.g., replicate, duplicate, etc.) nucleic acid thereby generating more copies of the nucleic acid in a sample. Molecular amplification comprises nucleic acid amplification, enzymatic amplification (e.g., PCR), isothermal amplification, and / or other alternative amplification methods that has been developed in the field.

[0049] As used herein, the terms “polymerase chain reaction” or “PCR” refers to a type of molecular or nucleic acid amplification that amplify or generate more copies of a nucleic acid template. The method of PCR can be used in conjunction with a method to detect, identify, and / or quantify the nucleic acid. The term “PCR” used herein intends to cover all different types of PCR, including, for example, sequential PCR and real-time PCR., or reverse transcription PCR (RT-PCR).

[0050] As used herein, the term “biological sample” means a sample containing nucleic acids / biological agents such as clinical (e.g., cell fractions, mucus membrane, nasal swab, whole blood, plasma, serum, urine, tissue, cells, etc.), agricultural, environmental (e.g., soil, mud, minerals, water, air), food, forensic, or any other biological samples. The sample may include infectious agents, such as, for example, viral, bacterial or parasitical infectious agents. With “whole blood,” it is meant blood such as it is collected, e.g., by venous sampling, e.g. containing white and red cells, platelets, plasma, and any infectious agents that may be present. The clinical samples may be from human or animal origin. The sample analyzed can be solid or liquid in nature. It is evident when solid materials are used, these are first dissolved in a suitable solution as known in the art.

[0051] As used herein, the term “nucleic acid” refers to DNA molecules, e.g., cDNA or genomic DNA, RNA molecules, e.g., mRNA, DNA-RNA hybrids, and analogs of DNA or RNA produced using nucleotide analogs. Nucleic acid molecules comprise nucleotides, oligonucleotides, double-stranded DNA, single-stranded DNA, multi-stranded DNA, complementary DNA, genomic DNA, non-coding DNA, messenger RNA (mRNA), singlestranded RNA, microRNA (miRNA), and nuclear body small molecules. It may be RNAAttorney Docket No. 61070-708601(snoRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), small interfering RNA (siRNA), heteronuclear RNA (hnRNA), or small hairpin RNA (shRNA).Data Security

[0052] The present disclosure provides methods and systems for securing data comprising personal health information. Regulations and privacy concerns may necessitate certain personal health information of patients, e.g., medical records or other identifiable health information, held in electronic systems to be secured and only accessible by authorized medical institutions and providers. Patient identifiable information may comprise names, birthdates, genders, geographic identifiers, dates, phone numbers, fax numbers, email addresses, social security numbers, medical record numbers, health plan beneficiary numbers, account numbers, certificate or license numbers, vehicle identifiers and serial numbers, device identifiers and serial numbers, web uniform resource locators (URLs), internet protocol (IP) address numbers, biometric identifiers (including finger, retinal, and voice prints), photographic images, or any other unique identifying number, characteristic, or code. Health record information may comprise billing information, emails, appointment scheduling apps, imaging results, blood test results, diagnoses, health provider visit information, doctors’ notes, other medical information of a patient, or any data used in the course of medical care. Electronic health record information is health record information that is created, stored, transmitted, or received electronically. Such electronic health record information may be stored on one or more computing devices or networks. Electronic health record information may require increased cybersecurity to protect the sensitive information from hacking or other unauthorized use. The present disclosure provides methods and systems for segregating health record information from non-health record data in multiple cloud environments in the context of point-of-care testing, in order to reduce the likelihood of unauthorized access to health record data. In some cases, health record information may be segregated from other data in a protected information cloud environment, which may be protected by firewalls and other data security measures. In the present disclosure, health record information stored in the protected information cloud environment is not accessed by the point-of-care device or its software.

[0053] In an aspect, the present disclosure provides a system for secure patient data handling. The system may comprise an instrument configured to test patient samples from a plurality of patients thereby producing test data. In some cases, no health record information or patient unique identifying information of any of the plurality of patients is received, stored, or accessed at or by the instrument. The system may also comprise an operating deviceAttorney Docket No. 61070-708601configured to be used with the instrument. The operating device may comprise software for operating the instrument. The operating device may be configured to receive test data from the instrument but may not receive, store, or access the health record information of any of the plurality of patients. The operating device may be further configured to interact with the instrument, a first cloud environment, and a second cloud environment. The first cloud environment may be configured to store health record information of the plurality of patients. The second cloud environment may be configured to receive the test data from the operating device and process the test data, thereby generating processed test data. The second cloud environment may be further configured to send the processed test data to the first cloud environment, thereby linking the processed test data of each of the plurality of patients with the health record information of each of the plurality of patients. In some cases, the software for operating the instrument may be configured to facilitate communications between the instrument and each of the first and second cloud environments. In some embodiments, the first cloud environment may be configured to prevent unauthorized access to the health record information of any of the plurality of patients using one or more network security measures. In some cases, the one or more network security measures may comprise a firewall.

[0054] In some embodiments, the software for operating the instrument may be configured to interact with the first cloud environment to link the health record information of a select patient with the test data of the select patient produced by the instrument. In some embodiments, the software for operating the instrument may be configured to receive patient unique identifying information to identify a patient and link the select patient with the select patient’s health record information stored in the first cloud environment. In some cases, the patient unique identifying information may comprise a patient’s name, date of birth, and / or gender. In some cases, the patient’s name, date of birth, and gender may be used by the software to link the patient with their test results and health record information.

[0055] In some cases, the software for operating the instrument may be configured to delete the patient unique identifying information after the patient unique identifying information has been received for a time duration. In some cases, the time duration may range from about 12 hours to about 48 hours. In some embodiments, the patient unique identifying information accessed by the software for operating the instrument is deleted after no more than about 24 hours. In some embodiments, the patient unique identifying information accessed by the software for operating the instrument is deleted after no more than about 12 hours. In some embodiments, the patient unique identifying information accessed by the software forAttorney Docket No. 61070-708601operating the instrument is deleted after no more than about 2 days. In some embodiments, the patient unique identifying information accessed by the software for operating the instrument is deleted after no more than about 3 days. In some embodiments, the patient unique identifying information accessed by the software for operating the instrument is deleted after no more than about 4 days. In some embodiments, the patient unique identifying information accessed by the software for operating the instrument is deleted after no more than about 5 days. In some embodiments, the patient unique identifying information accessed by the software for operating the instrument is deleted after no more than about 6 days. In some embodiments, the patient unique identifying information accessed by the software for operating the instrument is deleted after no more than about 7 days. In some embodiments, the patient unique identifying information accessed by the software for operating the instrument is deleted after no more than about 8 days. In some embodiments, the patient unique identifying information accessed by the software for operating the instrument is deleted after no more than about 9 days. In some embodiments, the patient unique identifying information accessed by the software for operating the instrument is deleted after no more than about 10 days.

[0056] In some cases, the software for operating the instrument is not configured to access the patient unique identifying information. In some cases, the software for operating the instrument is walled off from accessing the patient unique identifying information. In some cases, the software for operating the instrument may receive an encounter identification key or barcode to identify a select patient and link the select patient with the select patient’s health record information stored in the first cloud environment. In some embodiments, the software for operating the instrument does not access any health record information or patient unique identifying information. In some cases, only a barcode as described elsewhere herein is used to link the patient with their health record information and test results.

[0057] In some embodiments, the patient unique identifying information, test results, and health record information may all be stored in separate tables in a database or in separate databases. Patient identifying information may be separated using, for example, Virtual Private Database (VPD) policies that may restrict access based on organization. These VPD policies can mask sensitive fields such as patient ID or name for unauthorized users. This may prevent database administrators from viewing unmasked patient data, and / or block cross-organization access even if the application is compromised.

[0058] The database may implement a two-schema architecture comprising an engineering / test data schema and a patient data schema for PHI. Patient identifyingAttorney Docket No. 61070-708601information, health records, and test data may be stored in separate databases and accessed through a secure API architecture. In some embodiments, the software for operating the instrument does not access the patient’s health record information stored in the protected first cloud environment.

[0059] In some embodiments, the software for operating the instrument does not relay the unique patient identifying information of the patient to or from the instrument. In some cases, the unique patient identifying information is used only by the software for operating the instrument, and the instrument itself does not access any unique patient identifying information.

[0060] In some embodiments, the operating device may be a tablet computer, laptop computer, desktop computer, or any other type of computing device.

[0061] In some embodiments, the first cloud environment or the second cloud environment may comprise one or more servers. In some embodiments, the first cloud environment and the second cloud environment may be segregated from each other. In some embodiments, the first cloud environment and the second cloud environment may be compartmentalized within an integrated cloud environment. In some embodiments, the second cloud environment may be configured to receive and analyze the test data produced by the instrument to produce a diagnostic result.

[0062] In some embodiments, the health record information of the plurality of patients comprises protected health information (PHI).

[0063] In some embodiments, the operating device may be configured to be operated by an operator using a graphical user interface in the software to run a test on the instrument. In some cases, an operator identity (ID) information may be assigned to the operator. In some cases, the operator ID information may be stored in the first cloud environment. In some cases, the operator ID information may be verified when the operator starts the test on the instrument.

[0064] In some embodiments, the first cloud environment may be in communication with a government agency healthcare data monitoring portal. In some cases, the health record information of the plurality of patients may be transmitted with the processed test data from the first cloud environment to the government agency healthcare data monitoring portal for patient population tracking purposes.

[0065] In some cases, the second cloud environment may be further configured to store and use barcode information, instrument telemetry data, log files, algorithms, or any combination thereof for data processing. The second cloud environment may be configured to process theAttorney Docket No. 61070-708601instrument telemetry data and log files to enable monitoring and proactive servicing of the instrument, using at least in part failure mode models, component wear and tear monitoring and predictions, or over the air updates to extend component life of the instrument, or any combination thereof.

[0066] In some cases, the test data may be processed in the second cloud environment. In some cases, the second cloud environment may be configured to process the test data by executing the algorithms on the test data, thereby producing processed test data. In some cases, the test data may comprise PCR test data. In some cases, the algorithms may be used to determine cycle threshold values and interpret the cycle threshold values to process the PCR test data, thereby producing processed PCR test data.

[0067] In some cases, the second cloud environment may be configured to transmit software or firmware updates to the instrument and / or the software for operating the instrument.

[0068] In some embodiments, the software for operating the instrument may be further configured to store the test data. In some cases, the test data may be stored on the software for operating the instrument for up to about 50 test runs, for up to about 100 test runs, for up to about 150 test runs, for up to about 200 test runs, for up to about 250 test runs, for up to about 300 test runs, for up to about 500 test runs, for up to about 700 test runs, for up to about 1000 test runs, or more. In some cases, the test data may be stored on the software for operating the instrument for up to about 24 hours, up to about 48 hours, up to about 72 hours, up to about 4 days, up to about 5 days, up to about 6 days, or up to about 7 days or more.

[0069] In some embodiments, the first cloud environment may be configured to interface with an electronic health record (EHR) system. In some cases, the health record information of the plurality of patients may be stored in the EHR system. In some cases, the first cloud environment may be operably connected to the EHR system via a Health Level 7 (HL7) or Fast Healthcare Interoperability Resources (FHIR)-based application programming interface (API). In some cases, the first cloud environment and the EHR system may be used to coordinate EHR workflows. In some cases, the first cloud environment and the EHR system may be used for patient services which may include tracking of the plurality of patients in the EHR system based on identities of the plurality of patients. In some cases, the first cloud environment and the EHR system may be used for encounter services which include locating active encounters based on the identities of the plurality of patients. In some cases, the first cloud environment and the EHR system may be used for personnel services which may include locating and storing operator ID information.Attorney Docket No. 61070-708601

[0070] In some embodiments, the system may further comprise a third cloud environment. The third cloud environment may comprise manufacturing information for single-use test components used in the instrument, instrument manufacturing information, or any combination thereof. In some cases, the manufacturing information for the single-use test components or the instrument manufacturing information may be provided to the software for operating the instrument to track a manufacturing or recall status of the single-use test components or the instrument.

[0071] In some cases, the single-use test components may comprise single-use discs used in a PCR instrument. In some cases, the status of a single-use disc may be validated prior to performing a test on the PCR instrument by linking the single-use disc with the manufacturing or recall status of the single-use disc stored in the third cloud environment.

[0072] In an aspect, the present disclosure provides a method for secure patient data handling. The method may comprise providing an instrument configured to test patient samples from a plurality of patients thereby producing test data, wherein no health record information of any of the plurality of patients is received, stored, or accessed at or by the instrument. The method may further comprise using an operating device with the instrument. The operating device may comprise software for operating the instrument. The operating device may be used to receive the test data from the instrument but not receive, store, or access the health record information of any of the plurality of patients. The operating device may be further used to interact with the instrument, a first cloud environment, and a second cloud environment. The method may further comprise using the first cloud environment to store the health record information of the plurality of patients. The method may further comprise using the second cloud environment configured to receive test data from the operating device and process the test data thereby generating processed test data. The method may further comprise sending the processed test data from the second cloud environment to the first cloud environment, thereby linking the processed test data of each of the plurality of patients with the health record information of each of the plurality of patients.

[0073] In an aspect, the present disclosure provides a method of using an instrument to test patient samples. The method may comprise receiving one or more test samples by the instrument, using the instrument to obtain or collect test data from the one or more test samples, and producing a test result by the instrument. The instrument may receive the one or more test samples from a plurality of patients. In some cases, no health record information of the plurality of patients is received, stored, or accessed at or by the instrument.Point-of-Care InstrumentsAttorney Docket No. 61070-708601

[0074] Point-of-care testing is medical testing done close to the site of patient care, where patient care or treatment is provided. Point-of-care testing may provide rapid turnaround of test results, generating test results quickly so that appropriate treatment may be provided. Point-of-care testing may provide advantages over traditional laboratory testing, which typically involves multiple steps that take a significant amount of time. These multiple steps may comprise collecting samples from a patient at the patient care location, transporting the samples to a centralized laboratory or testing location, subjecting the samples to processing steps, and then returning the result to the patient.

[0075] In order for a point-of-care instrument to be easily used in a clinic or other patient care location, the instrument may need to be small and portable in order to facilitate easy use by a clinician or healthcare provider in the point-of-care location. Point-of-care instruments may be handheld or benchtop. Imaging instruments, such as magnetic resonance imaging (MRI) instruments, computed tomography (CT) instruments, positron emission tomography (PET) instruments, and ultrasound instruments, may also be classified as point-of-care devices if they provide their results immediately.

[0076] There are many different possible point-of-care locations where the instrument may be located. Some of these locations include, but are not limited to, a hospital, a hospital laboratory, a doctor’s office, a pharmacy, an emergency room, a field location, or a clinic.

[0077] The present disclosure provides methods and systems for a point-of-care instrument interacting with multiple cloud environments, wherein the result may be processed and delivered to the patient within minutes or seconds. In some embodiments, the instrument is selected from the group consisting of a PCR instrument, an imaging instrument, or an instrument for detecting one or more biomarkers in the patient samples. In some cases, the point-of-care instrument is a PCR instrument. In some cases, the PCR instrument may be a rapid PCR instrument. In some cases, the PCR instrument may comprise a base station and one or more operating modules. In some cases, the PCR instrument may be configured to detect one or more biomarkers in a patient sample. In some cases, the point-of-care instrument is an imaging instrument. In some cases, the point-of-care instrument is any other instrument configured to detect one or more biomarkers in a patient sample. In some cases, the instrument configured to detect the one or more biomarkers in the patient samples may comprise an immunoanalyzer, an antigen test, an albumin analyzer, a blood lactate analyzer, a cardiac marker analyzer, a clinical chemistry analyzer, a coagulation analyzer, a creatinine analyzer, a C-reactive protein analyzer, or a blood glucose analyzer.Attorney Docket No. 61070-708601

[0078] In some cases, a patient sample is collected in a different location from a location of the instrument. In some cases, the patient samples may be collected in a separate location from the instrument and subsequently transported to the instrument to be tested. For example, a patient may collect a sample from his or herself at home using a kit. This may allow for increased privacy. In some cases, the sample may be anonymized to increase patient privacy. The sample may be collected at, for example, the patient’s home, a doctor’s office, a clinic, or a pharmacy and transported to an instrument in a separate location for testing. The instrument may be located at, for example, a doctor’s office, clinic, pharmacy, laboratory, or hospital. The sample collection and instrument locations may be less than about a mile apart, between about 1 mile and about 5 miles apart, between about 5 miles and about 10 miles apart, between about 10 miles and about 20 miles apart, or greater than 20 miles apart. The sample may be transported by the patient or the healthcare provider between the sample collection and instrument locations. The sample may be transported by a third party from the sample collection location to the instrument location for improved convenience. For example, a courier service may be used to transport the sample to the location of the instrument for testing. The courier service may be requested by the patient or healthcare provider using a mobile app or website. The patient or healthcare provider may then give the sample to the courier service for transport to the instrument. In some cases, a computer system may be used to determine availability and / or capacity of nearby instruments to determine which instrument the courier service may transport the sample to. This may ensure rapid sample processing time.Electronic Health Record Systems

[0079] The present disclosure provides methods for segregation of health record information from test results in a cloud computing system. Such health record information may be stored in one or more electronic health record (EHR) systems. An electronic health record may comprise an electronic version of a patient’s health history. Such electronic health records may comprise demographics, progress notes, problems, medications, vital signs, past medical history, immunizations, laboratory data, radiology reports, or test results. The present disclosure provides a method of linking and storing test results from a point-of-care instrument with a patient’s electronic health record, without the instrument having access to the electronic health record itself. Examples of EHR systems include Epic, Cerner, CareCloud, Athenahealth, eClinicalWorks, and Veradigm. The cloud system described herein may transmit test results to one of these or another EHR system.Attorney Docket No. 61070-708601

[0080] The protected health information cloud may be operably connected to the one or more EHR systems via an application programming interface (API), such as a Fast Healthcare Interoperability Resources (FHIR) API, an hl7v2 API, or a custom API. The protected health information cloud may be operably connected to the one or more EHR systems via other methods. FHIR is a standard for exchanging healthcare information electronically. FHIR comprises building blocks called Resources. All exchangeable content is defined as a Resource. Resources all have a common way of being defined and represented, a common set of metadata, and a human readable part. FHIR is built over an HTTP secure protocol. Types of Resources may include, but are not limited to, Patient, Encounter, Practitioner, Organization, Observation, DiagnosticReport, and Questionnaire. A list of different types of Resources may be found in the HL7 FHIR documentation. When a patient has an interaction with a healthcare provider, the provider may enter information about that interaction into the EHR system as an Encounter.Barcodes

[0081] The present disclosure may comprise data transmission between software for operating a point-of-care instrument and one or more cloud environments. In some cases, data transmission between different cloud environments may occur. In some cases, data transmission between the software and the one or more cloud environments may involve using one or more barcodes or keys. For example, a single-use PCR disc used in the context of a point-of-care PCR instrument may contain a barcode to link the single-use PCR disc with manufacturing information about it located in the cloud system. In some cases, an operator of the instrument may use a barcode to verify their identity.

[0082] A barcode may be a linear barcode or a matrix barcode. A linear barcode may be UPC, EAN, CODE 39, CODE 128, ITF, CODE 93, Codabar, Databar, or MSI Plessey. A matrix barcode may be a quick response (QR) code, a data matrix, a PDF417, or an Aztec. A barcode may be scanned using a barcode scanner or camera with barcode-scanning software. A barcode may be scanned using a centralized operator application used with the device.Instruments

[0083] The present disclosure relates to an instrument, a rotatable disc, a method for preparing and processing samples, and a method for performing sample analysis, e.g., nucleic acid amplification such as polymerase chain reaction (PCR). In some embodiments, the instrument may be a rapid PCR device, e.g., a device that processes samples rapidly and returns a result immediately, as compared to a conventional PCR device. A conventional PCR device may take about three hours to produce a result. By contrast, a rapid PCR deviceAttorney Docket No. 61070-708601may take as little as about 15 minutes to about 30 minutes to produce a result. In some embodiments, the instrument comprises a thermocycling device comprising one or more reaction chambers. A nucleic acid-containing sample can be processed and / or analyzed within the one or more reaction chambers, e.g., in a PCR reaction. In some embodiments, the instrument further comprises a heating chamber for sample preparation. Samples may be heated in this heating chamber prior to further processing and analysis in the plurality of reaction chambers. In some embodiments, the method for preparing and processing samples may comprise heating the sample in hyperbaric heating conditions to inactivate one or more nucleic acid amplification inhibitors prior to nucleic acid amplification. In some embodiments, the method for preparing and processing samples may comprise using a thermocycling device as described herein to amplify and analyze a nucleic acid.

[0084] In the present disclosure a method of ultra-fast real-time polymerase chain reaction (PCR) for detecting the presence or absence of a target nucleic acid in a biological sample may be used. In one aspect, the method comprises: (a) loading a sample into a loading chamber on a rotatable disc, the rotatable disc further comprising a plurality of reaction chambers and a channel fluidly connecting the loading chamber to the plurality of reaction chambers; wherein the reaction chambers are loaded with a PCR reagent mixture comprising a primer and a fluorescent probe; wherein the sample flows to the plurality of reaction chambers via the channel thereby filling the reaction chambers following loading of the sample; (b) contacting the channel within the rotatable disc with a sealer, thereby sealing the channel and preventing fluid communication between the plurality of reaction chambers after filling; (c) rotating the rotatable disc to bring the plurality of reaction chambers adjacent to a first heating element maintained at a first temperature, thereby denaturing the target nucleic acid in the sample if present, thereby producing a denatured target nucleic acid; (d) rotating the rotatable disc to bring the plurality of reaction chambers adjacent to a second heating element maintained at a second temperature, thereby annealing the primer to the denatured target nucleic acid and replicating the denatured target nucleic acid; (e) exposing the plurality of reaction chambers to an excitation light of a first wavelength, thereby exciting the fluorescent probe; and (f) repeating steps (c) through (e) for multiple cycles and measuring an emission light of a second wavelength from the plurality of reaction chambers, wherein if emission light of a second wavelength is detected, the sample comprises the target nucleic acid.

[0085] In some embodiments, the present disclosure may comprise an instrument wherein the instrument comprises pairs of heating blocks (FIG. 1, 104, 105, and 106) that are arranged atAttorney Docket No. 61070-708601the same radius as a plurality of reaction chambers (e.g., cuvettes) (FIG. 1, 103) on the rotatable disc. In some embodiments, the rotatable disc may comprise a cuvette insert, wherein the cuvette insert comprises the plurality of reaction chambers (e.g., cuvettes). In some embodiments, the plurality of reaction chambers (e.g., cuvettes) (FIG. 1, 103) rotates between each heating block and stops at the location of each block for a dwelling time necessary for the corresponding PCR denaturing, annealing, or elongation steps.

[0086] In some embodiments, the reaction chambers (e.g., cuvettes) on the rotatable disc may be designed and manufactured to be filled and sealed before thermocycling. In some embodiments, the rotatable disc may comprise a cuvette insert, wherein the cuvette insert may comprise the reaction chambers (e.g., cuvettes). In some embodiments, the ultra-fast thermocycling of the present disclosure may be performed after the reaction chamber or the plurality of reaction chambers are solidly sealed from the atmosphere. The reaction chambers may, before sealing, be openly connected via microfluidic connections to an upper chamber. The reaction chambers may be filled via this microfluidic connection.

[0087] In some embodiments, the reaction chambers may be formed by sealing two thin polymer films together (FIG. 3A, FIG. 3B). For example, but not by way of limitation, one film (FIG. 3A 301) may be thermoformed to define reaction chamber shape and size (FIG.3B 303) as well as a channel (FIG. 3B 304). For example, but not by way of limitation, the second film may be a flat film (FIG. 3A 302), which may be used to laminate and seal the thermoformed film.

[0088] In some embodiments, the channel is formed by a thermoformed film. This thermoformed film can be heated in order to seal the channel. The channel can be heat sealed by compressing the thermoformed film composing the ceiling of the channel against the sealing film composing the floor of the channel.

[0089] In one aspect of the present disclosure, three heating blocks (e.g., a first heating block (FIG. 1 104), a second heating block (FIG. 1 105), and a third heating block (FIG. 1 104)) are set to three different temperatures (e.g., a first temperature, a second temperature, and a third temperature) corresponding to a denaturation temperature (e.g., about 90°C to about 99°C), an annealing temperature (e.g., about 50°C to about 70°C), and an elongation temperature (e.g., about 70°C to about 75°C). In some embodiments, the three heating blocks comprise a radial length, wherein the radial lengths are designed to correspond to a ratio of time favorable for denaturation, annealing, and elongation steps. The instrument may thereby perform the PCR amplification process while the rotatable disc rotates at a constant speed above the fixed heating blocks, and may keep physical contact with the block during theAttorney Docket No. 61070-708601entire process. In some embodiments, the disclosure comprises two heating blocks (e.g., a first heating block (FIG. 5504) and a second heating block (FIG. 5505)) set at two different temperatures (e.g., a first temperature and a second temperature) corresponding to a denaturation temperature (e.g., about 90°C to about 99°C) and an annealing / elongation temperature (e.g., about 50°C to about 75°C). In this embodiment, the instrument may thereby perform the annealing and elongation PCR steps with the same heating block at the same temperature.

[0090] In some embodiments, the instrument further comprises an optic head (FIG. 1, 107; FIG. 5, 506, FIG. 6A, 604) that excites and detects fluorescence inside the reaction chambers while in rotation. In some embodiments, the excitation source is a light source encompassing the wavelength of the fluorophore of interest (e.g., LASER or LED). In some embodiments, the fluorophore of interest is selected from FAM (e.g., 495 nm / 520 nm), SUN (e.g., 538 nm / 554 nm), TEX 615 (e.g., 596 nm / 613 nm), or Cy5 (e.g., 648 nm / 667 nm).

[0091] In some embodiments, each of the plurality of reaction chambers (FIG. 2, 209) is connected to an upstream mixing chamber (FIG. 2, 207) and to the adjacent reaction chamber (FIG. 2, 209) via a channel (FIG. 2, 208). In some embodiments, the channel comprises a thin plastic film (e.g., a sealing film) sealed on the rotatable disc. In some embodiments, the thin plastic film (e.g., the sealing film) is in direct contact with the material of the rotatable disc (e.g., hard plastic disc). For example, but not by way of limitation, the channel may not have any depth, and a sample liquid may be forced through by applying a high centripetal force to the rotatable disc.

[0092] In some embodiments, the rotatable disc comprises different chambers (e.g., a loading chamber FIG. 2, 203, also referred to as a heating chamber herein; a metering chamber FIG.2, 205; or a mixing chamber, FIG. 2, 207) linked by a channel (e.g., a channel comprising fluidic canals) (FIG. 1, 102) to accomplish metering and PCR reagent mixing after sample heating (e.g., hyperbaric heating). In some embodiments, and not by way of limitation, after extraction, nucleic acids may be brought to the plurality of reaction chambers (e.g., cuvettes) (FIG. 1, 103; FIG. 2, 209) via the channel (FIG. 1, 108; FIG. 2, 208). In some embodiments, the RT-PCR reagents are stored in the mixing chamber in a lyophilized form. Samples may be treated via heating in the loading chamber 203, metered into metering chamber 205, mixed with PCR lyophilized reagent inside chamber 207, and then flowed to the reaction chambers (e.g., cuvettes) 209 via channel 208. In some embodiments, the PCR primers and fluorescent probes are stored in the plurality of reaction chambers 209 in a driedAttorney Docket No. 61070-708601format and are reconstituted when a solution containing the nucleic acid of interest is forced through the channel and fills the plurality of reaction chambers (e.g., cuvettes).

[0093] In some embodiments, the channel is sealed between each of the plurality of reaction chambers after filling each reaction chamber with liquid, thereby preventing evaporation and escape of liquid when the reaction chambers are heated to a high temperature. In some embodiments, the channel is sealed with an electromagnetic source, such as but not limited to a LASER light mounted on a trail. In some embodiments, the channel is sealed by applying pressure and heat to the channel by, for example, a heat sealer (FIG. 7B, 701 to FIG. 7D, 701).

[0094] In some embodiments, the present disclosure relates to a method wherein the analytical device described herein is used to rapidly temperature cycle a volume of about 10 to about 100 pl of PCR or RT-PCR reagents in each reaction chamber. In the method described herein, at most about 6 fluorophores per reaction chamber may be monitored simultaneously. In some embodiments, the method comprises filling the reaction chambers with PCR or RT-PCR reagents via the channel using centripetal force generated by rotating the rotatable disc. In some embodiments, the reaction chambers are filled by spinning the rotatable disc at from about 1,000 RPM to about 15,000 RPM. In some embodiments, after the reaction chambers are filled, the method further comprises sealing the reaction chambers by applying a heat source across the channel. In some embodiments, the sealing film is sealed to the thermoformed film across the channel by pressing two vis a vis blocks against the rotatable disc; see comparison between element 701 of FIG. 7B to FIG. 7D.

[0095] In some embodiments, the instrument further comprises a heating chamber for sample preparation of a nucleic acid containing sample prior to processing and analysis by PCR. In some embodiments, the heating chamber is a part of or connected to the rotatable disc comprising the reaction chambers. In some embodiments, the heating chamber is connected to a microfluidics network that can transfer a heat-treated sample to a mixing chamber, wherein the heat-treated sample can be mixed with PCR reagents, and further transferred to one or more reaction chambers wherein the nucleic acid amplification reactions are performed.

[0096] In some embodiments, the instrument for performing PCR may comprise a base station and one or more operating modules. In some cases, the software for operating the instrument can serve as the point of communication between the PCR instrument and the first and second cloud environments.Attorney Docket No. 61070-708601

[0097] In some embodiments, the instrument may comprise an imaging instrument. In some cases, the imaging instrument may be an MRI machine, a CT scanner, a PET scanner, or an ultrasound device. In some cases, the imaging instrument may be any other type of medical imaging instrument. In some cases, the patient samples comprise medical imaging samples, e.g., a magnetic resonance imaging (MRI) scan, a computed tomography (CT) scan, a positron emission tomography (PET) scan, or an ultrasound scan.

[0098] In some embodiments, the instrument may comprise any instrument configured to detect one or more biomarkers in the patient samples. In some cases, the patient samples comprise samples taken to detect one or more biomarkers of the plurality of patients using the instrument.

[0099] In some embodiments, the instrument may comprise a PCR instrument. The PCR instrument may be configured to test the patient samples. The PCR instrument may comprise a base station and one or more operating modules. In some embodiments, testing the patient samples with the PCR instrument may comprise inserting a PCR disc into the PCR instrument, loading a patient sample into the PCR disc, and running a spin recipe on the PCR instrument, thereby producing the test data comprising PCR data. The PCR test data may then be sent from the instrument to the software for operating the instrument, and then further sent from the software for operating the instrument to the second cloud environment for processing.

[0100] In some embodiments, the PCR data may be processed in the second cloud environment. In some embodiments, the second cloud environment may further comprise disc barcode information, PCR instrument telemetry data and log files, and algorithms to be used for data processing. In some cases, the PCR instrument telemetry data and log files are associated with one or more components of the instrument selected from the group consisting of heaters, a channel sealer, induction heaters, a valving laser, an optics module, a centrifuge motor, a lift mechanism, grippers, and a tray. In some cases, the second cloud environment is configured to process the PCR instrument telemetry data and log files to enable monitoring and proactive servicing of the PCR instrument, using at least in part failure mode models, component wear and tear monitoring and predictions, or over-the-air updates to extend component life of the PCR instrument.

[0101] In some embodiments, processing the PCR data in the second cloud environment may comprise executing the algorithms used for data processing to process the PCR test data thereby producing processed PCR test data. In some cases, executing the algorithms used for data processing to process the PCR test data comprises analyzing the PCR test data toAttorney Docket No. 61070-708601determine cycle threshold values and interpreting the cycle threshold values to process the PCR test data into processed PCR test data for the plurality of patients. In some cases, the processed test results of a patient may subsequently be sent to the first cloud environment to be re-associated with health record information of the patient.Methods for Sample Heating or Sample Preparation

[0102] The present disclosure provides a system for testing patient samples of a plurality of patients at a clinical test or POC location. In some cases, the patient samples may comprise bodily samples selected from the group consisting of a blood sample, a lacrimal fluid sample, a saliva sample, a mucus sample, a sputum sample, a feces sample, a cerebrospinal fluid sample, and a urine sample. In some cases, the patient samples may comprise biological samples comprising a nucleic acid. Examples of biological samples comprising a nucleic acid may be bodily samples (e.g., saliva or mucus) or cells (e.g., a bacterial cell, a fungal cell, or a mammalian cell). The present disclosure provides methods for sample preparation of a nucleic acid in a bodily sample that do not involve extraction, isolation, or other forms of purification of the nucleic acid from the bodily sample. The present disclosure provides methods of heating a nucleic acid sample in hyperbaric heating conditions, thereby preparing it for further processing or analysis. In some embodiments, the heat-treated sample may undergo further sample processing or analysis. The present disclosure provides methods of inactivating molecular amplification inhibitors in the sample (e.g., RNAses present in saliva or mucus), thereby preparing the sample for further processing. The heat-treated sample or inactivated sample may be used for nucleic acid detection and / or analysis using PCR analysis or a biological (e.g., diagnostic) assay or any of the nucleic acid analysis methods disclosed elsewhere herein.

[0103] The present disclosure further provides methods of analyzing the nucleic acid in the biological sample, comprising preparing the sample using a method of the present disclosure and subsequently analyzing the nucleic acid. The methods of sample preparation described herein may prepare the sample for molecular amplification of the nucleic acid in the sample. In some embodiments, the methods described herein may improve the efficiency of nucleic acid analysis by improving the efficiency of molecular amplification. The methods described herein may reduce the degree of nucleic acid degradation and improve the detectability of the nucleic acid or molecular amplification products thereof for analysis.

[0104] In some embodiments, analyzing the nucleic acid comprises analyzing a molecular amplification product of the nucleic acid (e.g., DNA copies of RNA produced during PCR amplification of the RNA in the sample using reverse transcriptase). For example, in someAttorney Docket No. 61070-708601embodiments, detecting the nucleic acid may comprise detecting a molecular amplification product of the nucleic acid. In some embodiments, sequencing the nucleic acid comprises sequencing a molecular amplification product of the nucleic acid. In some embodiments, genotyping the nucleic acid comprises genotyping a molecular amplification product of the nucleic acid. One of ordinary skill in the art will understand that many means for analyzing the nucleic acid are known in the art, all of which are compatible with methods of the present disclosure and contemplated herein.

[0105] In some embodiments, the molecular amplification comprises enzymatic amplification. In some embodiments, the molecular amplification comprises isothermal amplification. In some embodiments, the nucleic acid amplification comprises polymerase chain reaction (“PCR”), loop mediated isothermal amplification (LAMP), nucleic acid sequence based amplification (NASBA), self-sustained sequence replication (3 SR), strand displacement amplification (SDA), multiple displacement amplification (MDA), rolling cycle amplification (RCA), ligase chain reaction (LCR), helicase dependent amplification (HAD), ramification amplification method (RAM), transcription-mediated assay (TMA), Nicking enzyme amplification reaction (NEAR), Recombinase Polymerase Amplification (RPA), or whole genome amplification (WGA).

[0106] In some aspects, the methods of the present disclosure comprise heating a treatment sample. A “treatment sample”, as referred to herein, is a sample (e.g., an aqueous solution or suspension) containing at least a nucleic acid and optionally reagents such as enzymes or chelating agents. In certain embodiments, a treatment sample may be a biological sample of nucleic acids collected from a subject and diluted with water or a buffer and optionally including the one or more reagents. The biological sample may be a bodily sample, such as saliva or mucus. The biological sample may comprise a cell (e.g., an unlysed cell). In certain embodiments, the sample of nucleic acid collected from a subject may be isolated or purified, e.g., isolated or purified from the cell, proteins, or other biologies in the biological sample, prior to dilution and / or addition of reagents. In certain embodiments, the sample of nucleic acid collected from a subject may not be isolated or purified, e.g., isolated or purified from the cell, proteins, or other biologies in the biological sample, prior to dilution and / or addition of reagents.

[0107] In some aspects, the method comprises heating the treatment sample to a temperature above 100 degrees Celsius in a closed heating chamber in hyperbaric heating conditions. For instance, the closed heating chamber may substantially prevent air and vapor from entering or leaving the chamber. In some cases, there is negligible air flow in and out of the closedAttorney Docket No. 61070-708601heating chamber. The closed heating chamber may remain closed during hyperbaric heating. In some embodiments, “hyperbaric heating conditions” referred to herein are conditions in which heating generates a higher pressure inside the closed heating chamber than outside the closed heating chamber. In some aspects, the heating of the treatment sample occurs at a temperature ramp rate, for example, from 6 degrees Celsius per second to 20 degrees Celsius per second. In some aspects, the methods of the present disclosure comprise heating the treatment sample from a first temperature to a second temperature above 100 degrees over a ramp time.

[0108] In some aspects, the methods of the present disclosure comprise analyzing a nucleic acid in a bodily sample selected from: blood, lacrimal fluid, saliva, mucus, sputum, feces, cerebrospinal fluid, and urine. In one aspect, the method comprises providing the bodily sample and heating a treatment sample comprising the bodily sample. In some embodiments, the nucleic acid is not extracted, isolated, or otherwise purified from the bodily sample.

[0109] In some aspects, the treatment sample comprising the nucleic acid further comprises one or more reagents selected from: a chelating agent, a single stranded nucleic acid binding protein, and a reducing agent. In some embodiments, the treatment sample comprises a chelating agent, a single stranded nucleic acid binding protein, and a reducing agent.

[0110] In some aspects, the methods described herein comprise heating a treatment sample in a closed heating chamber in hyperbaric conditions to a temperature above 100 degrees Celsius. In some embodiments, the method comprises hyperbaric heating the treatment sample to a temperature above 100 degrees Celsius. The temperature may be above the boiling point of water.[oni] In some aspects, the methods described herein comprise heating a treatment sample comprising said nucleic acid in a closed heating chamber in hyperbaric conditions from a first temperature to a second temperature above 100 degrees Celsius over a ramp time, thereby producing a heat-treated sample. The closed heating chamber may remain closed (e.g., substantially preventing air from entering or exiting the chamber) during heating from the first temperature to the second temperature. In some embodiments, the treatment sample does not boil in the hyperbaric conditions at the second temperature above 100 degrees.

[0112] In some embodiments, the method of analyzing the nucleic acid further comprises, after (a), maintaining said treatment sample at the second temperature for a maintenance time prior to a cooling time. During the maintenance time, the closed heating chamber may remain closed (e.g., substantially prevent air and vapor from entering or leaving the chamber).Attorney Docket No. 61070-708601During the cooling time, the closed heating chamber may remain closed (e.g., substantially prevent air and vapor from entering or leaving the chamber).

[0113] In some aspects, heating the treatment sample in a closed chamber generates a pressure inside the chamber.

[0114] In some aspects, the present disclosure provides methods of heating a treatment sample comprising a nucleic acid. In some embodiments, the nucleic acid is DNA. In some embodiments, the nucleic acid is RNA. In some embodiments, the nucleic acid is derived from a eukaryotic cell or a prokaryotic cell. In some embodiments, the nucleic acid is derived from a virus. In some embodiments, the nucleic acid is selected from a viral nucleic acid, a bacterial nucleic acid, a protozoan nucleic acid, a eukaryotic nucleic acid, and a fungal nucleic acid. In some embodiments, the nucleic acid is a viral nucleic acid.

[0115] In some embodiments, the treatment sample comprising a bodily sample comprising the nucleic acid is heated in a closed heating chamber in hyperbaric conditions. In some embodiments, the bodily sample comprises a substance selected from blood, plasma, serum, lacrimal fluid, saliva, mucus, sputum, feces, cerebrospinal fluid, lymph fluid, bile, synovial fluid, cyst fluid, ascites, pleural fluid, ocular fluid, interstitial fluid, cervical fluid, and urine. In some embodiments, the bodily sample is selected from blood, lacrimal fluid, saliva, mucus, sputum, feces, cerebrospinal fluid, and urine. In some embodiments, the bodily sample comprises mucus. In some embodiments, the bodily sample comprises body fluid sample, tissue, or cell of a subject. In some embodiments, the nucleic acid is not extracted, isolated, or otherwise purified from the bodily sample.

[0116] In some aspects, the bodily sample may be collected from a subject (e.g., a human). The bodily sample may be collected via nasopharyngeal swab, cervical swab, or nasal swab from said subject. In some cases, the bodily sample may comprise a pathogen or a portion thereof. In some embodiments, the pathogen or portion thereof is selected from a virus or a portion thereof, a bacterium or a portion thereof, a protozoon or a portion thereof, a yeast or a portion thereof, and a fungus or a portion thereof. In some embodiments, the pathogen is a blood-borne pathogen or portion thereof. In some embodiments, the pathogen is a respiratory pathogen or portion thereof.

[0117] In some embodiments, the method of analyzing the nucleic acid further comprises at least one of the following: detecting said nucleic acid, sequencing said nucleic acid, and genotyping said nucleic acid. In some embodiments, the method of analyzing the nucleic acid further comprises at least two of the following: detecting said nucleic acid, sequencing said nucleic acid, and genotyping said nucleic acid. In some embodiments, the method ofAttorney Docket No. 61070-708601analyzing the nucleic acid further comprises: detecting said nucleic acid, sequencing said nucleic acid, and genotyping said nucleic acid. In some embodiments, the method of analyzing the nucleic acid comprises detecting the nucleic acid via fluorescence detection.

[0118] In some embodiments, the volume of the treatment sample is the total volume of the mixture of the biological sample, the collection buffer, to one or more additives prior to hyperbaric heating.

[0119] In some aspects, the treatment sample comprises one or more additives. The one or more additives may comprise a chelating agent, a single-stranded nucleic acid binding protein, a reducing agent, a protease, a nuclease inhibitor, or combination thereof.

[0120] In some embodiments, the treatment sample further comprises a single stranded nucleic acid binding (SSB) protein. In some embodiments, the single stranded nucleic acid binding protein is thermostable.

[0121] Additional details and examples of using hyperbaric conditions to process samples are disclosed in International Application No. PCT / US23 / 67879, the entire content of which is incorporated herein by reference.Methods for Sample Processing or Analysis

[0122] The present disclosure provides a method for sample processing and / or analysis. For example, the method can be used to subject a sample comprising a nucleic acid to nucleic acid amplification such as real-time polymerase chain reaction (PCR). In some embodiments, centripetal microfluidics are applied to fluid within a PCR instrument. One advantage of centripetal microfluidics, for example, is that the centrifugal pumping is applied to the fluid without the need to any direct connection to the instrument, helping to prevent contamination. In some embodiments, the present disclosure provides a method of amplifying nucleic acid in a PCR instrument comprising a rotatable disc. In some embodiments, the method comprises maintaining one or more reaction samples in place in one or more reaction chambers during heating and substantially preventing evaporation in the one or more reaction chambers. In some embodiments, the method comprises transferring a sample comprising the target nucleic acid to be analyzed to one or more reaction chambers in 30 seconds or less and subsequently, sealing the one or more reaction chambers. In some embodiments, sealing a reaction chamber substantially prevents any liquid or steam from escaping the reaction chamber.

[0123] In some embodiments, the method comprises loading a sample comprising a target nucleic acid (e.g., a bodily sample, a treatment sample, or a heat-treated sample) into a loading chamber on the rotatable disc. In some cases, the sample is heated in a separate heating chamber (e.g., in hyperbaric heating conditions) prior to loading into the loadingAttorney Docket No. 61070-708601chamber. In some cases, the loading chamber is or comprises a heating chamber, and the method comprises heating the sample comprising the target nucleic acid in the loading chamber in a hyperbaric condition to produce a processed sample (e.g., a heat-treated sample), as described elsewhere herein.

[0124] In some embodiments, the loaded sample is a treatment sample as described elsewhere herein (e.g., a nucleic acid containing sample prior to treatment by hyperbaric heating) and is directly heated in the loading chamber. In some cases, the sample comprising the target nucleic acid that is heated comprises a bodily sample selected from the group consisting of: a blood sample, a lacrimal fluid sample, a saliva sample, a mucus sample, a sputum sample, a feces sample, a cerebrospinal fluid sample, and a urine sample.

[0125] During sample heating, the sample may be in a sealed or closed heating chamber. In some embodiments, following heating, an exit valve is opened to release the sample from the loading chamber (e.g., heating chamber). The exit valve may be opened by electromagnetic means. For example, the exit valve may be a laser valve that is opened using a laser. In some embodiments, the method comprises rotating the rotatable disc such that the processed sample exits the loading chamber from the exit valve via centrifugation forces. In some cases, the rotatable disc further comprises a reaction chamber and a channel connecting the loading chamber to the reaction chamber. In some cases, the rotatable disc is rotated in order to transfer the processed sample from the loading chamber to the reaction chamber via the channel. In some cases, the processed sample flows from the loading chamber to one or more intermediate chambers before flowing to the reaction chamber via the channel.

[0126] For example, rotating the rotatable disc may cause the processed sample to flow from the loading chamber into a collection chamber (e.g., a metering chamber) that is immediately downstream of the loading chamber via a channel. In some embodiments, the method for sample processing and / or analysis further comprises metering a specific volume of sample to be processed or analyzed (e.g., a nucleic acid containing sample, bodily sample, treatment sample, or post-hyperbaric heating treatment sample). In some embodiments, sample metering occurs after loading the sample into the loading chamber on the rotatable disc. In some embodiments, sample metering occurs after initial sample preparation (e.g., treatment by hyperbaric heating). The sample metering can occur in a metering chamber, which can be the loading chamber where the sample is loaded or a separate collection chamber to where the sample flows after initial sample preparation (e.g., hyperbaric heating in a heating chamber.Attorney Docket No. 61070-708601

[0127] In some embodiments, the method for sample processing and / or analysis further comprises mixing the sample to be processed or analyzed with a PCR reagent mixture (e.g., RT-PCR reagent mixture

[0128] In some embodiments, the method for sample processing and / or analysis comprises transferring the target nucleic acid into a reaction chamber (e.g., a cuvette) or a plurality of reaction chambers (e.g., a plurality of cuvettes) on the rotatable disc. In some cases, the combined target nucleic acid and PCR reagent mixture is transferred from the reagent mixing chamber to the one or more reaction chambers. The release of the combined mixture from the reagent mixing chamber can be controlled by a valve (e.g., a laser valve). In some embodiments, the nucleic acid and PCR reagent mixture is transferred from the reagent mixing chamber into the reaction chamber or the plurality of reaction chambers via centrifugation forces. In some cases, the centrifugation forces are generated using spin speeds from about 1000 rpm to about 3000 rpm.

[0129] In some embodiments, the method for sample processing and / or analysis further comprises sealing the one or more reaction chambers after transferring the mixture comprising the target nucleic acid into the one or more reaction chambers. In some embodiments, sealing the reaction chambers substantially prevents the mixture from exiting the chamber. In some embodiments, the rotatable disc comprises a cuvette insert that comprises the one or more reaction chambers and a cuvette channel by which the sample containing the target nucleic acid flows into a plurality of reaction chambers (e.g., cuvettes). The one or more reaction chambers (e.g., cuvettes) can be sealed using a heat sealer. In some embodiments, the rotatable disc is contacted with a sealer, thereby sealing the channel after the processed sample flows into the one or more reaction chambers. In some embodiments, the channel is heat sealed at a temperature from 200 to 300 degrees Celsius. In some embodiments, the channel is sealed by using the heat sealer to compress or crush the channel. In some embodiments, sealing the cuvette channel substantially prevents fluid communication between the plurality of reaction chambers.

[0130] In some embodiments, the method for sample processing and / or analysis further comprises amplifying the target nucleic acid in the one or more reaction chambers. In some embodiments, the nucleic acid amplification reactions are carried out after heat sealing of the one or more reaction chambers. In some embodiments, the cuvette insert comprising the one or more reaction chambers is first pressed between the 95°C temperature block for 5 to 30 seconds to activate the DNA polymerase. In some embodiments, the cuvette insert is moved between different heating elements (e.g., temperature blocks) to carry out differentAttorney Docket No. 61070-708601thermocycling steps. In some embodiments, thermocycling comprises rotating the rotatable disc to bring the reaction chamber (e.g., cuvette) adjacent to a first heating element maintained at a first temperature, thereby denaturing the target nucleic acid in the sample. In some embodiments, thermocycling further comprises rotating the rotatable disc to bring the reaction chamber adjacent to a second heating element maintained at a second temperature, thereby annealing the primer to the denatured nucleic acid and replicating the target nucleic acid. In some embodiments, thermocycling further comprises rotating the rotatable disc to bring the plurality of reaction chambers (e.g., cuvettes) adjacent to a third heating element maintained at a third temperature, thereby replicating the target nucleic acid.

[0131] In some aspects, the present disclosure provides a method for sample analysis. The method can comprise: (a) loading a sample comprising a target nucleic acid into a loading chamber on a rotatable disc. The rotatable disc can further comprise a plurality of reaction chambers and a channel connecting the loading chamber to the plurality of reaction chambers. The sample can flow to the plurality of reaction chambers via the channel following loading of the sample. The method can further comprise (b) contacting the rotatable disc with a sealer. The sealer can seal the channel and prevent fluid communication between the plurality of reaction chambers after filling. In certain embodiments, the sealer is incorporated into the PCR instrument. The method may further comprise (c) rotating the rotatable disc to bring the plurality of reaction chambers adjacent to a first heating element maintained at a first temperature. The first heating element can be used to denature the target nucleic acid in the sample. The method can further comprise (d) rotating the rotatable disc to bring the plurality of reaction chambers adjacent to a second heating element maintained at a second temperature. The second heating element can be used to anneal the primer to the denatured target nucleic acid and replicate the denatured target nucleic acid. The method may further comprise (e) exposing the plurality of reaction chambers to an excitation light of a first wavelength. The method may further comprise (f) measuring an emitted light of a second wavelength from the plurality of reaction chambers. In some cases, some of the steps, e.g., steps (c) through (f) described herein, can be repeated until the emitted light is measured at an intensity indicating the presence of the target nucleic acid.

[0132] In some embodiments, prior to (b), the method further comprises rotating the rotatable disc to generate a sufficient centripetal force on the sample to cause the sample to flow through the channel and into the plurality of reaction chambers. In some embodiments, the sufficient centripetal force is generated by spinning the rotatable disc from about 500 RPM to about 15,000 RPM.Attorney Docket No. 61070-708601

[0133] In some embodiments, the channel is defined by two plastic sheets welded together by two parallel lines. In some embodiments, the channel comprises a thin plastic film with diameter ranging from about 1pm to about 1mm. In some embodiments, the channel defines a lumen with a diameter ranging from about 1 m to about 1mm. In some embodiments, the channel comprises a thermoplastic material that seals the channel when heated to a target temperature. In some embodiments, the target temperature comprises from about 110 degrees C to about 300 degrees C.

[0134] In some embodiments, the reaction chambers FIG. 5503 are defined by a thermoplastic film FIG. 5501 sealed to a sealing film FIG. 5502.

[0135] In another embodiment, the reaction chambers are defined by a film FIG. 4407 sealed in both side by two films, thermoformed film FIG. 4401 and a sealing film FIG. 4 402. In this embodiment, reaction chamber depth is not defined by thermoforming but by the thickness of film FIG. 4407 which is from about 0.1 to about 1mm.

[0136] In some embodiments, the sample is mixed with a primer complementary to at least a portion of the target nucleic acid pre-loaded within the plurality of reaction chambers. In some embodiments, the plurality of reaction chambers further comprises a probe, and wherein the sample is further mixed with the probe.

[0137] In some embodiments, the plurality of reaction chambers is each aligned at the same radial distance from a center of the rotatable disc and are equally spaced from each other.

[0138] In some embodiments, subsequent to rotating the rotatable disc to bring the plurality of reaction chambers (e.g., cuvettes) adjacent to a second heating element, the method of the present disclosure further comprises rotating the rotatable disc to bring the plurality of reaction chambers (e.g., cuvettes) adjacent to a third heating element maintained at a third temperature. In some embodiments, the first temperature is maintained for a first period of time and the second temperature is maintained for a second period of time. In some embodiments, the third temperature is maintained for a third period of time.

[0139] In some embodiments, the method further comprises stabilizing the rotatable disc at the first temperature for the first period of time, the second temperature for the second period of time and / or the third temperature for the third period of time. In some embodiments, stabilizing comprises clamping the rotatable disc between a first heating block and a second heating block of the first heating element, the second heating element or the third heating element. In some embodiments, subsequent to clamping the rotatable disc, the method further comprises unclamping the rotatable disc from the first heating block and the second heating block of the first, second, or third heating element.Attorney Docket No. 61070-708601

[0140] In some embodiments, the excitation light is supplied by an optic head or a plurality of optic heads. In some embodiments, the optic head or plurality of optic heads further comprise one or more wavelength filters to change the first wavelength or the plurality of wavelengths for the excitation light. In some embodiments, the emission light is measured on a first fluorescence detector or a plurality of fluorescence detectors. In some embodiments, the first detector or plurality of fluorescence detectors comprises one or more wavelength channels to measure an emission intensity.

[0141] Another aspect of the present disclosure is directed to a method for multiplexed realtime amplification and detection of a plurality of target sequences in a rotatable disc comprising a reaction chamber, the method comprising: (a) loading a sample comprising the plurality of target sequences into the reaction chamber (e.g., cuvette); wherein the sample is mixed with a primer and / or a probe stored within the reaction chamber, (b) thermal cycling the sample mixed with the PCR reaction mixture by rotating the rotatable disc, thereby sequentially bringing the reaction chamber in proximity of a plurality of heating elements positioned adjacent to the rotatable disc, wherein each of plurality of heating elements is maintained at a denaturing temperature, an annealing temperature, or an elongation temperature; and (c) detecting a plurality of fluorescence signals from the combined sample and first PCR reaction mixture.

[0142] In some embodiments, the rotatable disc further comprises a loading chamber in fluid communication with the reaction chambers through a channel. In some embodiments, the method further comprises loading the sample into the loading chamber. In some embodiments, the channel is defined by two plastic sheets welded together by two parallel lines. In some embodiments, the channel comprises a thin plastic film with a z dimension from about 1pm to about 1mm.

[0143] In some embodiments, the reaction chamber (e.g., cuvette) comprises one or more reaction chambers. In some embodiments, each of the reaction chamber comprises a volume of from about 5 pL to about 100 pL and further comprises a depth from about 0.1 mm to about 1.0 mm. In some embodiments, the reaction chamber comprises a depth of at most about 0.25 mm.

[0144] In some embodiments, loading the sample into the reaction chamber comprises rotating the rotatable disc, thereby generating a sufficient centripetal force on the sample to cause the sample to flow through the channel and into the reaction chamber. In some embodiments, the sufficient centripetal force is generated by spinning the rotatable disc from about 500 RPM to about 15000 RPM.Attorney Docket No. 61070-708601

[0145] In some embodiments, prior to thermocycling the sample, the method further comprises contacting the rotatable disc with a sealer, thereby sealing the channel and preventing fluid communication the reaction chamber (e.g., cuvette). In some embodiments, the sealer is housed within an instrument for real-time PCR, thereby enabling a full sampleanswer system by integrating a microfluidic sample preparation system with a nucleic acid processing system. In some embodiments, each reaction chamber is sealed by contact or noncontact means to avoid evaporation and escape of the heated liquid. In some embodiments, sealing of the channel is achieved via heat and pressure, via LASER welding or via ultrasonic welding. In some embodiments, sealing of the channel is achieved via heat and pressure, such as, but not limited to, by a heat sealer. In some embodiments, the sealer is a heat sealer. In some embodiments, the sealer comprises a first element configured to provide a thermal energy and a pressure on the rotatable disc and a second element configured to provide a counter force to the pressure. In some embodiments, contacting the rotatable disc with the sealer comprises applying the pressure on the rotatable disc such that the channel deforms.Computer Systems

[0146] The present disclosure provides computer systems that are programmed to implement methods of the disclosure. FIG. 17 shows a computer system 1701 that is programmed or otherwise configured to interact with a point-of-care device and transmit data between the device and multiple cloud environments. The computer system 1701 can regulate various aspects of the cloud architecture of the present disclosure, such as, for example, segregating data between a protected information cloud and an engineering cloud used for processing of data from the point-of-care device. The computer system 1701 can be an electronic device of a user or a computer system that is remotely located with respect to the electronic device. The electronic device can be a mobile electronic device.

[0147] The computer system 1701 includes a central processing unit (CPU, also “processor” and “computer processor” herein) 1705, which can be a single core or multi core processor, or a plurality of processors for parallel processing. The computer system 1701 also includes memory or memory location 1710 (e.g., random-access memory, read-only memory, flash memory), electronic storage unit 1715 (e.g., hard disk), communication interface 1720 (e.g., network adapter) for communicating with one or more other systems, and peripheral devices 1725, such as cache, other memory, data storage and / or electronic display adapters. The memory 1710, storage unit 1715, interface 1720 and peripheral devices 1725 are in communication with the CPU 1705 through a communication bus (solid lines), such as a motherboard. The storage unit 1715 can be a data storage unit (or data repository) for storingAttorney Docket No. 61070-708601data. The computer system 1701 can be operatively coupled to a computer network (“network”) 1730 with the aid of the communication interface 1720. The network 1730 can be the Internet, an internet and / or extranet, or an intranet and / or extranet that is in communication with the Internet. The network 1730 in some cases is a telecommunication and / or data network. The network 1730 can include one or more computer servers, which can enable distributed computing, such as cloud computing. The network 1730, in some cases with the aid of the computer system 1701, can implement a peer-to-peer network, which may enable devices coupled to the computer system 1701 to behave as a client or a server. The network 1730 may allow for transmission of data between multiple cloud environments.

[0148] The CPU 1705 can execute a sequence of machine-readable instructions, which can be embodied in a program or software. The instructions may be stored in a memory location, such as the memory 1710. The instructions can be directed to the CPU 1705, which can subsequently program or otherwise configure the CPU 1705 to implement methods of the present disclosure. Examples of operations performed by the CPU 1705 can include fetch, decode, execute, and writeback.

[0149] The CPU 1705 can be part of a circuit, such as an integrated circuit. One or more other components of the system 1701 can be included in the circuit. In some cases, the circuit is an application specific integrated circuit (ASIC).

[0150] The storage unit 1715 can store files, such as drivers, libraries and saved programs. The storage unit 1715 can store user data, e.g., user preferences and user programs. The computer system 3001 in some cases can include one or more additional data storage units that are external to the computer system 1701, such as located on a remote server that is in communication with the computer system 1701 through an intranet or the Internet.

[0151] The computer system 1701 can communicate with one or more remote computer systems through the network 1730. For instance, the computer system 1701 can communicate with a remote computer system of a user (e.g., a tablet interfacing between a point-of-care device and multiple cloud environments). Examples of remote computer systems include personal computers (e.g., portable PC), slate or tablet PC’s (e.g., Apple® iPad, Samsung® Galaxy Tab), telephones, Smart phones (e.g., Apple® iPhone, Android-enabled device, Blackberry®), or personal digital assistants. The user can access the computer system 1701 via the network 1730.

[0152] Methods as described herein can be implemented by way of machine (e.g., computer processor) executable code stored on an electronic storage location of the computer systemAttorney Docket No. 61070-7086011701, such as, for example, on the memory 1710 or electronic storage unit 1715. The machine executable or machine readable code can be provided in the form of software.During use, the code can be executed by the processor 1705. In some cases, the code can be retrieved from the storage unit 1715 and stored on the memory 1710 for ready access by the processor 1705. In some situations, the electronic storage unit 1715 can be precluded, and machine-executable instructions are stored on memory 1710.

[0153] The code can be pre-compiled and configured for use with a machine having a processer adapted to execute the code, or can be compiled during runtime. The code can be supplied in a programming language that can be selected to enable the code to execute in a pre-compiled or as-compiled fashion.

[0154] Aspects of the systems and methods provided herein, such as the computer system 1701, can be embodied in programming. Various aspects of the technology may be thought of as “products” or “articles of manufacture” typically in the form of machine (or processor) executable code and / or associated data that is carried on or embodied in a type of machine readable medium. Machine-executable code can be stored on an electronic storage unit, such as memory (e.g., read-only memory, random-access memory, flash memory) or a hard disk. “Storage” type media can include any or all of the tangible memory of the computers, processors or the like, or associated modules thereof, such as various semiconductor memories, tape drives, disk drives and the like, which may provide non-transitory storage at any time for the software programming. All or portions of the software may at times be communicated through the Internet or various other telecommunication networks. Such communications, for example, may enable loading of the software from one computer or processor into another, for example, from a management server or host computer into the computer platform of an application server. Thus, another type of media that may bear the software elements includes optical, electrical and electromagnetic waves, such as used across physical interfaces between local devices, through wired and optical landline networks and over various air-links. The physical elements that carry such waves, such as wired or wireless links, optical links or the like, also may be considered as media bearing the software. As used herein, unless restricted to non-transitory, tangible “storage” media, terms such as computer or machine “readable medium” refer to any medium that participates in providing instructions to a processor for execution.

[0155] Hence, a machine readable medium, such as computer-executable code, may take many forms, including but not limited to, a tangible storage medium, a carrier wave medium or physical transmission medium. Non-volatile storage media include, for example, opticalAttorney Docket No. 61070-708601or magnetic disks, such as any of the storage devices in any computer(s) or the like, such as may be used to implement the databases, etc. shown in the drawings. Volatile storage media include dynamic memory, such as main memory of such a computer platform. Tangible transmission media include coaxial cables; copper wire and fiber optics, including the wires that comprise a bus within a computer system. Carrier-wave transmission media may take the form of electric or electromagnetic signals, or acoustic or light waves such as those generated during radio frequency (RF) and infrared (IR) data communications. Common forms of computer-readable media therefore include for example: a floppy disk, a flexible disk, hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD or DVD-ROM, any other optical medium, punch cards paper tape, any other physical storage medium with patterns of holes, a RAM, a ROM, a PROM and EPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wave transporting data or instructions, cables or links transporting such a carrier wave, or any other medium from which a computer may read programming code and / or data. Many of these forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution.

[0156] The computer system 1701 can include or be in communication with an electronic display 3035 that comprises a user interface (UI) 1740 for providing, for example, an interface to run a test on a point-of-care device and transmit data between the device and multiple cloud servers. Examples of UFs include, without limitation, a graphical user interface (GUI) and web-based user interface.

[0157] Methods and systems of the present disclosure can be implemented by way of one or more algorithms. An algorithm can be implemented by way of software upon execution by the central processing unit 1705. The algorithm can, for example, run a test on a point-of-care device and transmit data between the device and multiple cloud servers.Data Analysis

[0158] PCR data may be processed as follows. First, raw fluorescent data may be acquired for each cycle. Second, fluorescent signal from each cuvette may be detected for each cycle using peak or integration algorithms. A raw curve may be plotted, showing an increase in fluorescence over all PCR cycles. Third, background subtraction and other methods may be used to normalize all PCR curves. Fourth, algorithms may be used to detect when the system begins to achieve exponential growth indicative of a PCR reaction. The cycle value at which this growth begins may be recorded. Fifth, growth for control curves may be checked toAttorney Docket No. 61070-708601determine if the result is valid. Finally, results of whether the result was detected, not detected, or invalid for each target may be reported.

[0159] FIG. 8 shows a schematic of a point-of-care PCR device 801 integrated with the cloud system described herein. The first step of the procedure may be an operator taking a patient sample on the PCR device and running a test disc. A computer application 802 on an internet-connected device may act as an operator application and interact with the PCR device. The internet-connected device may be an iPad. The internet-connected device may be a laptop computer. Raw data may be sent from the operator application to the cloud system 804 for processing, as indicated by the arrow 803. The cloud system 804 may manage all devices and access to all results. As indicated with the arrow 805, the processed results may be sent from the cloud system back to the operator application. As indicated with the arrow 807, processed results may be stored in the cloud and accessible in one or more electronic health record (EHR) systems 806. As indicated by 808, patient may get notifications about their test results on an internet-connected device, such as a mobile phone, through the EHR systems. As indicated in 809, processed results may be stored in the cloud and may be accessible through the cloud operator portal 810. As indicated with the arrow 811, the process of running the PCR test and transmitting the data to the cloud may take less than 10 minutes.

[0160] FIG. 9 illustrates a workflow for a cloud system integrated with a point-of-care PCR device. First, the user may start a test 901 on the instrument / operator app 921 by scanning or entering an operator ID 902. The operator ID may be confirmed during operator setup and stored through a call to a protected information cloud environment 916 that holds protected health information. The operator ID may be confirmed by calling a personnel services portion of the protected information cloud environment 916. Next, the patient ID or demographics of the patient (e.g. name, birthday, gender) may be entered 903. The patient ID may be linked with an encounter between the patient and a healthcare provider 918. The encounter may also have an ID. The patient ID and encounter information may be located through a call to encounter services 913 and patient services 914 portions of the protected information cloud environment 916. The encounter may be found by searching the patient services and encounter services portions with an encounter match algorithm 917. The patient services 914 and encounter services 913 portions may access patient and encounter information from the EHR 806. The patient ID and encounter ID can be located either before or after the test is performed. A PCR disposable disc as described herein may have a quick response (QR) code attached to uniquely identify it. Information about each disc may be stored in the manufacturing cloud environment. Next, the disc quick response (QR) code may be scannedAttorney Docket No. 61070-708601or entered 904. The disc status may be verified through a call 911 to the manufacturing cloud environment 1005. The disc QR code, patient ID or demographic information, and operator ID may then be sent 910 to the protected information cloud environment 916 for storage and to match 912 to patient, encounter, or personnel information located in the EHR system 806.The sample may then be loaded into the disc 905. The disc may then be loaded into the PCR device and the test may be run 906. The disc QR code, raw test results, and device data may then be sent 907 to another cloud environment, the engineering cloud 922. The data may be processed and results generated 908 in the engineering cloud 922. The test results may then be sent to the protected information cloud environment 916 to be reassociated 909 with the patient ID stored in the protected information cloud environment. The test results may be sent 919 to the EHR system 806 using an FHIR API or a similar healthcare information standard, which formats the test results and writes them 920 to the EHR system 806.

[0161] FIG. 10 shows types of data in different environments in the cloud system. The different data types are as follows: (A) operating module ID, (B) base station ID, (C) disc ID, (D) operator ID information, (E) patient ID or other demographic information, (F) raw test data, (G) instrument log files related to a specific test, (H) processed test data, (I) disc status, (J) demographic information from the EHR, and (K) instrument firmware. Before a test is run, a call may be made from the operator app 802 to the manufacturing cloud 1005 to check the status of the disc being run and see if there are any updates to the instrument 801 or firmware available. Thus, (A)-(B)-(C)-(K) may be sent to the manufacturing cloud 1005 and disc status information (I) and firmware updates (K) may be returned. Additionally, the disc ID (C), operator ID (D), and patient ID (E), may be sent before a test to the protected information cloud 916. Following a test run, (A)-(B)-(C)-(F)-(G) may be sent for processing to the engineering cloud 922. The results algorithm may be used to transform the raw test data (F) into processed test results data (H). (A)-(B)-(C)-(F)-(G)-(H) may be stored as de-identified data in the engineering cloud 922. The de-identified data may be used for instrument proactive service and customer support. Processed test results and disc IDs (C)-(H) may be sent from the engineering cloud 922 to the protected information cloud 916 where they may be reassociated with patient and operator information (D)-(E) and stored as a FHIR resource in the protected information cloud. This FHIR resource of (C)-(D)-(E)-(H) may then be sent to: 1) the customer portal for viewing by the healthcare provider or test operator, 2) the operator app 802 for viewing at the instrument location (only the last 250 results may be viewable), and / or 3) sent as an observation to Electronic Health Record systems 806 through FHIR or similar healthcare interoperability standards. The protectedAttorney Docket No. 61070-708601information cloud or EHR systems 806 may also pull additional EHR patient demographic information (J) and send it, along with the processed test results (H), for public health reporting 1010. The engineering cloud 922 and manufacturing cloud 1005 may interact with the cloud engineering portal 1020. The engineering cloud 922 and protected information cloud 916 may interact with the cloud operator portal 1025.

[0162] FIG. 11 illustrates a workflow for a cloud system integrated with a point-of-care PCR device 801. The PCR device 801 may have a base station 1105 with a QR scanner and system-on-module (SOM) for connecting to an operator application 802. The base station may comprise a bottom part of the instrument that provides power for up to 4 operating modules 1110. The base station may receive power from a power outlet and route it to the up to 4 operating modules 1110. The SOM may comprise a small computer that houses firmware and software to operate the up to 4 operating modules 1110. The operator app 802 may talk to the SOM via Bluetooth. The PCR device 801 may have up to 4 operating modules on a single base unit. The PCR device 801 may connect to the operator application 802 using Bluetooth. The operator application 802 may connect to a clinic or hospital network 1115. The clinic / hospital network may have a firewall 1120 that protects personal health information from being shared. Information may be transmitted through the clinic / hospital network 1115 to and from the operator app 802, which can then itself communicate with the PCR device 801. The status of the PCR disc being used in a test may be transmitted to and from a manufacturing cloud 1005. A disc QR code, operator ID, test results, and device telemetry data may be transmitted to and from an engineering cloud 922. Finally, a disc QR code, patient data, and operator ID may be transmitted to and from a protected information cloud 916. Information may also be transmitted from the manufacturing cloud 1005 to the engineering cloud 922. Information may also be transmitted from the engineering cloud 922 to the protected information cloud 916, an operator portal 1025, and an engineering portal 1020. The protected information cloud can send data to the Centers for Disease Control (CDC) 1125 for government surveillance programs. The protected information cloud can also send data to EHR systems 806 through a FHIR API or other healthcare standard. EHR systems 806 can notify patients or report data to the state or federal government. The manufacturing cloud 1005 and engineering cloud 922 may not contain protected health information, while the protected information cloud may contain protected health information.

[0163] FIG. 12 shows a diagram of interactions between the manufacturing cloud 1005, the engineering cloud 922, and the protected information cloud 916. The manufacturing cloud 1005 may comprise instrument manufacturing information and disc manufacturingAttorney Docket No. 61070-708601information (e.g. lot information, expiration information, disc status). The engineering cloud 922 may comprise instrument log files, raw test data, test processing algorithms, updates, and deidentified test results. The manufacturing cloud 1005 and the engineering cloud 922 both may not contain protected health information. The protected information cloud 916 may comprise patient data, operator / user information, and electronic health record information and settings. The manufacturing cloud 1005 may interact with a user interface application, such as an engineering portal 1020, that sits on top of the manufacturing and engineering clouds 1005, 922 and pulls data from the different cloud environments. The engineering cloud 922 may interact with the engineering portal 1020 and the operator portal 1025. The protected information cloud 916 may interact with the operator portal 1025.

[0164] FIG. 13 shows interactions between the PCR device 801, a PCR disc 1301, and the manufacturing cloud 1005. The instrument 801 may transmit a device manufacturing ID, a device status, and manufacturing dates to the manufacturing cloud 1005. The PCR disc 1301 may transmit a disc manufacturing ID, a disc lot, a lot status, and manufacturing and expiration dates to the manufacturing cloud via a QR code that is scanned by the operator app 802. A production team may have access to the manufacturing cloud 1005 and may upload disc and device information during manufacturing. Disc lot information can be queried during a test run to ensure that the lot of that disc 1301 has not been recalled.

[0165] FIG. 14 shows data communicated with the engineering cloud 922 in a PCR device 801 system. Instrument telemetry and logs may be automatically sent to the engineering cloud 922 after each test run. This data can include information from all instrument subsystems, test information, and error logs. Raw test results may also be sent. Raw fluorescent signals may be automatically sent to the engineering cloud 922 and stored in object storage to retain data integrity. The engineering cloud 922 may then interact with the engineering portal 1020. All raw test data and test log files may be stored in object storage for traceability and data integrity. Algorithms to process the raw data into test results may also reside in the engineering cloud 922. Algorithms to process instrument telemetry and turn it into usable data may also be stored in the engineering cloud 922. All software / firmware code for instruments may be stored in the engineering cloud 922. Software / firmware code can be automatically downloaded by devices in the field following the release procedure.

[0166] FIG. 15 shows that instrument telemetry in a PCR device 801 system can be tracked for proactive service. All major instrument subsystems and test information may be tracked and telemetry transmitted to the engineering cloud. The PCR device 801 may produce logging and telemetry data across instrument subsystems. A PCR device 801 may compriseAttorney Docket No. 61070-708601PCR heaters, a channel sealer, induction heaters, a valving laser, an optics module, a centrifuge motor, a lift mechanism, grippers, a tray, a module, a system, and data from a run. Logging and telemetry data may be produced by the components of a PCR device 801. This data may be transmitted to the cloud system 804. Data may be used for instrument monitoring and proactive service 1501, including failure mode models, component wear and tear, and over-the-air updates to extend component life (e.g., increasing laser power by updating digital potentiometer settings). Failure mode models may comprise models developed through analysis of raw data from the PCR system components that indicate ways an instrument or component may fail at a future date. For example, if out-of-range currents coming from the laser diode are observed, a failure mode model may be generated. This failure mode model may show that if these currents are observed for a certain number of days, a likely failure of the laser may occur within a certain number of months.

[0167] FIG. 16 shows a PCR system’s 801 interaction with a protected information cloud 916. Patient and test information may be automatically sent to the protected information cloud 916 during run setup in the operator app 802. Patient and test information may include patient demographics, patient IDs, encounter IDs, operator ID, and disc ID. Information may then be sent from the protected information cloud to an electronic health records system 806.The electronic health records system 806 may have secure storage of protected health information and results data. It also may comprise an FHIR interoperability engine, EHR workflows, patient services (e.g., locating a patient in an EHR system given patient ID or demographic info), encounter services (e.g., locating active encounters given patient ID), and / or personnel services (e.g., locating and storing operator ID given operator info).

[0168] FIG. 18 shows a view of a possible embodiment of the operator app 802. The operator app may comprise a login screen 1801.

[0169] FIG 19 shows a view of a possible embodiment of the operator app 802. The operator app 802 may comprise information about positivity rate 1901, tests run 1905, and total errors 1910. The operator app may further comprise a task queue. The operator app may comprise a menu bar 1915 (shown on the left-hand side in this embodiment), with different elements. The menu bar may comprise different tabs such as the dashboard 1920 (current screen), tasks 1925, devices 1930, operators 1935, results 1940, and preferences 1945. In some embodiments, the organization or site name 1950 and operator name 1955 may be observed at the top of the screen.

[0170] FIG 20 shows a view of a possible embodiment of the operator app 802. The operator app may comprise a tasks tab 1925. In some cases, device, operator, and / or resultsAttorney Docket No. 61070-708601tasks can be checked or unchecked in boxes 2001. In some cases, operator additions, module additions, and test errors can be viewed.

[0171] FIG. 21 shows a view of a possible embodiment of the operator app. The operator app may comprise a devices tab 1930. The devices tab may display a list of the different devices that can be connected to the operator app 2101. A device may have a connection, serial number, site, location, modules, status, total number of tests, number of invalid tests, and / or number of errors displayed. A list of these tasks may also be displayed. This list may include modules added or hardware errors. In some cases, a user can filter the devices by site and location, number of modules per base, or module status (e.g., ready or not ready). The devices tab may also display an analytics box 2105 that shows the number of tests run, the number and percentage of positive tests, and / or the number of errors.

[0172] FIG. 22 shows a view of a possible embodiment of the operator app 802. In some embodiments, more information about a specific device 2201 as shown on the devices tab 1930 may be displayed on the operator app 802. In some embodiments, an image of a device 2205, a base station serial number 2210, a base station status 2215, a base station site and location 2220, a graph 2225 of tests 2230, invalid tests 2235, errors over different seasons 2240, and / or a list of modules 2245 can be shown. The image of the device may display a top module for the subject Dave and a middle module for the subject Rob. The screen may show hardware errors detected on the device, as shown at the top of the screen 2250. For example, the screen may show an error for the subject Rob, e.g., the middle module on the device, as shown at the bottom of the screen. The modules section may also show that the test for the subject Dave is complete.

[0173] FIG. 23 shows a view of a possible embodiment of the operator app 802. This view is similar to FIG. 21, but without the hardware error shown. In some cases, the modules section may show that a Bluetooth connection is required to display module status.

[0174] FIG. 24 shows a view of a possible embodiment of the operator app 802. This view shows the users tab 1935. The users tab 1935 may comprise a list of users 2401 with their user ID 2405, name 2410, user type (e.g., admin or operator) 2415, date added 2420, date last online 2425, total tests performed 2430, and / or location 2435. The users tab may also comprise a tasks-devices window 2440. The users may be filtered by operator ID, first or last name, site / location, or user type. The users tab may further comprise an analytics window 2445, which may show a number of new users, a number of users with errors, and / or a total number of users.Attorney Docket No. 61070-708601

[0175] FIG. 25 shows a view of a possible embodiment of the operator app 802. This screen may show information about a specific user. In this embodiment, the specific user shown is the user Paul McCartney. The information about a specific user may include boxes for user ID 2405, user type 2415, site 2501, location 2435, date added 2420, date last online 2425, and / or email address 2505. The information about a specific user may also include an operator ID / barcode 2510, which can be printed. Another box may show the total number of tests performed by this user 2515. The screen may further comprise a graph 2520 of tests 2525, invalid tests 2530, and / or errors over different seasons 2535. The screen may further comprise a reset password button 2540 and / or an archive button 2545.

[0176] FIG. 26 shows a view of a possible embodiment of the operator app 802. The operator app 802 may comprise a menu for adding a new user 2601. In some embodiments, operator details may be entered into the menu. Such details may include operator ID 2405, a select user type menu 2605, first name 2610, last name 2615, EHR username 2620, email (optional for operator) 2505, a select site menu 2625, and / or a select location menu 2630.

[0177] FIG. 27 shows a view of a possible embodiment of the operator app 802. The operator app may comprise a test results tab 1940. The test results tab 1940 may comprise a list of test results 2701. The list of test results may comprise a list of results, with with each result having a timestamp 2705, patient ID 2710, patient first name 2715, patient last name 2720, target (e.g., the virus being tested for, such as flu A, flu B, RSV, SC2, or rhinovirus) 2725, result (detected or not detected, for each virus being tested for) 2730, and / or operator / username 2735. The test results tab may comprise a tasks menu 2740 with invalid results that a user can click on to check. The test results tab may further comprise an analytics box 2445 showing a number of new users, a number of users with errors, and / or a total number of users. The results may be filtered with the filter menu 2745 by search ID / operator ID, search name (first name / last name), sites and location, and / or user type.

[0178] FIG. 28 shows a view of a possible embodiment of the operator app 802. The operator may comprise a screen with more information about a specific test result. This screen may comprise an operator ID box with the name 2410 and ID 2405 of the operator, a patient ID box with the patient’s ID 2701 and demographic information 2801, a disc ID box 2705, a disc number box 2710, and / or a box for notes 2715. The screen may further comprise a test result box 2720. For example, the test result may be shown as positive. In some cases, the test result box may display more information about the positive test result 2725, such as that it is a respiratory result, the date, time, site, location, base station number, and / or module serial number.Attorney Docket No. 61070-708601Operator Procedure

[0179] In an embodiment, a workflow performed by a user of a point-of-care PCR device integrated with a cloud system is described.

[0180] If the user wants to start a test, they may go to the home screen on the operator application. From the operator home screen, the user may either click “start test” or go to cancel the test. If the user goes to cancel the test, the operator application may prompt the user regarding whether the user wants to cancel the test and set up an electronic health record (EHR) system or proceed as is. If an EHR system is not set up in the cloud, the cloud system may send back a message that “patient EHR is not set up” to the operator app. The operator app may then prompt the user that EHR is not set up and may ask if the user wants to proceed with the test anyway.

[0181] If the user proceeds with the test as is, the operator app may ask the user to manually enter additional patient information such as patient ID, first / last name, date of birth, and gender. This additional patient information may then go to the sample ID screen.

[0182] If the user clicks “start test” on the operator app, the app may prompt the user about whether the user has an operator ID barcode. If the user does not have an operator ID barcode, the protected information cloud may check to see if the operator was found in the EHR system. If so, the protected information cloud may return the operator object back to the operator app. The user may then select the appropriate operator, and the operator app may store the EHR operator ID.

[0183] If the user does have an operator ID barcode, the operator ID barcode may either be scanned or manually entered. The operator app may then call the protected information cloud to verify that the user is valid. The protected information cloud may then query the operator database and send back a message to the app. In the protected information cloud query, the query may check whether the operator ID has been matched with the operator EHR username during operator setup. If the operator ID matches with the operator EHR username, this can verify that the operator is valid, and the system can then proceed to the next step.

[0184] If the operator ID does not match with the operator EHR username, the protected information cloud personnel service may call the EHR. The protected information cloud may check to see if the operator was found in the EHR. If so, the protected information cloud may return the operator object back to the operator app. The operator may select the appropriate operator. The operator app may store the EHR operator ID. If the operator is not found in the EHR, the system may go back again to query whether the user has the operator barcode.Attorney Docket No. 61070-708601

[0185] Once the operator information has been verified, the system may then go to the next step, the patient information screen. The system may then check whether the user has the encounter ID barcode. If so, the system may scan the encounter ID. If not, the user can manually select the patient by entering information such as encounter ID, patient ID, first / last name, date of birth, and gender. The app may then call the protected information cloud to verify that the patient exists.

[0186] The app may then check if EHR is set up in the cloud. If EHR is not set up in the cloud, the cloud may send back a message that “patient EHR is not set up” to the operator app. The operator app may then prompt the user that EHR is not set up and may ask if the user wants to proceed with the test anyway. If the user proceeds with the test as is, the operator app may ask the user to manually enter additional patient information such as patient ID, first / last name, date of birth, and gender. This additional patient information may then go to the sample ID screen.

[0187] If EHR is set up in the cloud, the protected information cloud may then locate the patient record in the EHR. First, the protected information cloud may search by demographics, patient ID, or encounter ID. If searching by encounter ID, the protected information cloud encounter service may call the EHR. If the encounter ID is not located, the protected information cloud may return an empty payload to the operator app. If the encounter ID is located, the protected information cloud may return a patient and encounter object back to the operator app, containing the patient ID, demographic information and / or encounter information. The operator app may then store the patient ID, demographic information, and / or encounter ID.

[0188] If searching by patient ID or demographics, the protected information cloud patient service may call the EHR. If the patient is not located in the EHR, the protected information cloud may return an empty payload to the operator app. If the patient is located in the EHR, the protected information cloud may return a patient object with the patient ID and / or demographic information to the operating app. The operator may then confirm the patient information. The protected information cloud encounter service may then call EHR and check whether encounter IDs within a specific criteria (e.g. date range, type) were located. If not, the protected information cloud may return an empty payload to the operator app. If so, the protected information cloud may return a patient object with all encounters listed (demographic and encounter information) back to the operator app. The operator may then select the encounter, and the operator app may store the encounter ID.Attorney Docket No. 61070-708601

[0189] Next, the operator app may check whether the patient encounter was located in the EHR. If not, the protected information cloud may send back a message to the operator app indicating that the patient EHR was not found. The operator app may then prompt the user that the EHR information was not found and may allow the user to edit information or proceed with current patient data. The operator app may then ask the operator whether they want to edit the patient info or proceed as is. If the operator wants to edit the patient info, the system may go back to the patient information screen. If the operator wants to proceed as is, the operator app may store patient demographic information but no encounter ID.

[0190] If the patient encounter was found in the EHR, the operator app may go to the sample ID screen. The app may then ask the user whether the user has a sample ID barcode to scan. If so, the sample ID may be scanned. If not, the sample ID may be manually entered.

[0191] The operator app may then proceed to the disc barcode screen. The user may grab a disc and remove it from the packaging. The user may check to see if the disc barcode is readable by the operator app. If so, the operator app may scan the disc barcode. If not, the disc barcode may be manually entered.

[0192] The operator app may then send the disc ID information to the manufacturing cloud. The manufacturing cloud may verify whether the disc barcode is valid by pulling data from the manufacturing cloud. If the disc barcode is invalid, the manufacturing cloud may send a message back to the operator app indicating that the barcode is not valid and giving a reason. The operator app may then inform the user why the disc is not valid and may give next steps. The app may then return to the disc barcode screen and the user may select a different disc.

[0193] If the disc barcode is valid, the manufacturing cloud may send a message back to the operator app indicating that the barcode is valid. The operator app may then send the operator ID, disc ID, and encounter ID to the protected information cloud.

[0194] The app may then proceed to the transfer sample screen. The user may load the sample into the disc and close the cap. The user may then scan or manually enter the disc barcode again to open the tray. The instrument may then open the loading tray. The user may load the disc into the instrument. The user may press the button to close the tray. The instrument may send a message to the operator app indicating that the tray is closed. The instrument may then run through the spin recipe. After the instrument finishes the spin recipe, it may send the raw test data to the operator app. While the spin recipe is proceeding, the instrument may send updates on test progress to the operator app at a fixed frequency. The operator app may show a “test in progress” screen. After the instrument finishes the spin recipe, the operator app may send the raw test data and log files to the engineering cloud. TheAttorney Docket No. 61070-708601engineering cloud may then evaluate the integrity of the raw data and log files to check if the data is valid.

[0195] If the data is not valid, the system may check whether the error is due to upload failure or something else. If it’s an upload error, the engineering cloud may require the data to be resent. If there are repeated upload errors, after failing a specified number of attempts, the operator app may show that there has been a failure to upload the data and may advise the user on next steps. If it’s another type of error, the engineering cloud may log the error and send an error code back to the operator app. The operator app may then display the error code and state what the user should do next.

[0196] If the data is valid, the operator app may then display that the test data is processing. The engineering cloud may convert the raw data to a processable format and generate cycle threshold values. The engineering cloud may then interpret the cycle threshold values and determine a test result. The engineering cloud may then send the results back to the operator app. The engineering cloud may send test data and log files to object storage. The operator app may show a “test completed” screen and display the results. The engineering cloud may then send the test results and disc barcode ID to the protected information cloud.

[0197] Test results for that disc barcode ID may then be posted in the protected information cloud. The test results may be put into temporary discrete data storage. Workflows in this cloud may be triggered as soon as test results are posted to the cloud to do the following: 1) associate the test result with the patient information provided earlier (e.g., patient ID, encounter ID, patient demographics, etc.) by using the disc ID as a primary key, 2) look up and locate the appropriate patient and encounter information in the EHR system if it was not provided or found previously. An observation service may then formulate an observation FHIR resource and store this in the protected information cloud. This resource can then be used to either directly post an observation to the appropriate EHR if the EHR accepts FHIR resources or convert the observation to an appropriate standard (hl7v2, etc.) and then post the observation to the EHR. If the post is successful, the protected information cloud may tag the results as successfully posted to the EHR. If the post is not successful, the protected information cloud may receive an error code and may update the test results with the error code.

[0198] If the error code was a developer error, the protected information cloud may move the test result to the developer queue. If the error code was an organizational admin error, the protected information cloud may move the test result to the organizational queue. If the errorAttorney Docket No. 61070-708601code was a retry error, the protected information cloud may move the test result to the retry queue.

[0199] From the organizational queue, the admin user may access and resolve all results in the organizational queue and attempt to resend to the EHR system. If the admin wants to release results to the EHR that were not successfully transmitted, the admin may log into the operator portal and view unreleased results in the queue. The admin may edit patient identifying information. Results, disc ID, and sample ID may not be edited. The admin may release results either individually or in batch format.

[0200] From the retry queue, the protected information cloud may attempt to resend results at a specified rate for a specified number of days. The workflow may then return to the observation service step.

[0201] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. It is not intended that the invention be limited by the specific examples provided within the specification. While the invention has been described with reference to the aforementioned specification, the descriptions and illustrations of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. Furthermore, it shall be understood that all aspects of the invention are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is therefore contemplated that the invention shall also cover any such alternatives, modifications, variations, or equivalents. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

Attorney Docket No. 61070-708601CLAIMS WHAT IS CLAIMED IS:

1. A system for secure patient data handling, the system comprising:an instrument configured to test patient samples from a plurality of patients thereby producing test data, wherein no health record information or patient unique identifying information of any of the plurality of patients is received, stored, or accessed at or by the instrument; andan operating device configured to be used with the instrument, wherein the operating device comprises software for operating the instrument, wherein the operating device is configured to receive the test data from the instrument but does not receive, store, or access the health record information of any of the plurality of patients, wherein the operating device is further configured to interact with the instrument, a first cloud environment, and a second cloud environment; andwherein the first cloud environment is configured to store the health record information of the plurality of patients;wherein the second cloud environment is configured to receive the test data from the operating device and process the test data thereby generating processed test data; andwherein the second cloud environment is further configured to send the processed test data to the first cloud environment, thereby linking the processed test data of each of the plurality of patients with the health record information of each of the plurality of patients.

2. The system of claim 1, wherein the instrument is configured to be used at a clinical testing or point-of-care location to test the patient samples.

3. The system of any one of claims 1 or 2, wherein the first cloud environment is configured to prevent unauthorized access to the health record information of any of the plurality of patients using one or more network security measures.

4. The system of claim 3, wherein the one or more network security measures comprises a firewall.Attorney Docket No. 61070-7086015. The system of any one of claims 1-4, wherein the software for operating the instrument is configured to facilitate communications between the instrument and each of the first and second cloud environments.

6. The system of any one of claims 1-5, wherein the software for operating the instrument is configured to interact with the first cloud environment to link the health record information of a select patient with the test data of the select patient produced by the instrument.

7. The system of any one of claims 1-6, wherein the software for operating the instrument is configured to receive patient unique identifying information to identify a select patient and link the select patient with the select patient’s health record information stored in the first cloud environment.

8. The system of claim 7, wherein the software for operating the instrument is configured to delete the patient unique identifying information after the patient unique identifying information has been received for a time duration.

9. The system of claim 8, wherein the time duration ranges from about 12 hours to about 48 hours.

10. The system of any one of claims 1-6, wherein the software for operating the instrument is not configured to access the patient unique identifying information.

11. The system of any one of claims 1-6 or 10, wherein the software for operating the instrument is walled off from accessing the patient unique identifying information.

12. The system of any one of claims 1-11, wherein the software for operating the instrument is configured to receive an encounter identification key to identify a select patient and link the select patient with the select patient’s health record information stored in the first cloud environment.

13. The system of any one of claims 1-12, wherein the patient unique identifying information, the health record information, and the test data are all stored in separate tables in a database or in separate databases.Attorney Docket No. 61070-70860114. The system of any one of claims 1-13, wherein the operating device comprises a tablet, a laptop computer, or any other type of computing device.

15. The system of any one of claims 1-14, wherein the operating device is configured to be operated by an operator using a graphical user interface in the software to run a test on the instrument.

16. The system of claim 15, wherein an operator identity (ID) information is assigned to the operator.

17. The system of claim 16, wherein the operator ID information is stored in the first cloud environment.

18. The system of claim 16 or 17, wherein the operator ID information is verified when the operator starts the test on the instrument.

19. The system of any one of claims 1-18, wherein the first cloud environment is configured to interface with an electronic health record (EHR) system.

20. The system of claim 19, wherein the health record information of the plurality of patients is stored in the EHR system.

21. The system of claims 19 or 20, wherein the first cloud environment is operably connected to the EHR system via a Health Level 7 (HL7) or Fast Healthcare Interoperability Resources (FHIR)-based application programming interface (API).

22. The system of any one of claims 19-21, wherein the first cloud environment and the EHR system are used to coordinate clinical workflows.

23. The system of any one of claims 19-22, wherein the first cloud environment and the EHR system are used for patient services which include tracking of the plurality of patients in the EHR system based on identities of the plurality of patients.

24. The system of any one of claims 19-23, wherein the first cloud environment and the EHR system are used for encounter services which include locating active encounters based on the identities of the plurality of patients.Attorney Docket No. 61070-70860125. The system of any one of claims 19-24, wherein the first cloud environment and the EHR system are used for personnel services which include locating and storing the operator ID information.

26. The system of any one of claims 1-25, wherein the first cloud environment is in communication with a government agency healthcare data monitoring portal.

27. The system of claim 26, wherein the health record information of the plurality of patients is transmitted with the processed test data from the first cloud environment to the government agency healthcare data monitoring portal for patient population tracking.

28. The system of any one of claims 1-27, wherein the instrument is selected from the group consisting of a polymerase chain reaction (PCR) instrument, an imaging instrument, and an instrument configured to detect one or more biomarkers in the patient samples.

29. The system of claim 28, wherein the instrument is the polymerase chain reaction (PCR) instrument.

30. The system of claim 28 or 29, wherein the PCR instrument comprises a base station and one or more operating modules.

31. The system of any one of claims 28-30, wherein the PCR instrument is a rapid PCR instrument.

32. The system of claim 28, wherein the instrument is the imaging instrument.

33. The system of claims 28 or 32, wherein the patient samples comprise imaging samples selected from the group consisting of a magnetic resonance imaging (MRI) scan, a computed tomography (CT) scan, a positron emission tomography (PET) scan, and an ultrasound scan.

34. The system of claim 28, wherein the instrument is the instrument configured to detect one or more biomarkers in the patient samples.

35. The system of claim 28 or 34, wherein the instrument configured to detect the one or more biomarkers in the patient samples comprises an albumin analyzer, a bloodAttorney Docket No. 61070-708601lactate analyzer, a cardiac marker analyzer, a clinical chemistry analyzer, a coagulation analyzer, a creatinine analyzer, a C-reactive protein analyzer, or a blood glucose analyzer.

36. The system of any one of claims 1-31 or 34-35, wherein the patient samples are selected from the group consisting of a blood sample, a lacrimal fluid sample, a saliva sample, a mucus sample, a sputum sample, a feces sample, a cerebrospinal fluid sample, and a urine sample.

37. The system of any one of claims 1-36, wherein a patient sample is collected in a different location from a location of the instrument.

38. The system of any one of claims 1-37, where the second cloud environment is further configured to store and use barcode information, instrument telemetry data, log files, algorithms or any combination thereof for data processing.

39. The system of claim 38, wherein the second cloud environment is configured to process the test data by executing the algorithms on the test data thereby producing processed test data.

40. The system of claim 39, wherein the test data comprises PCR test data.

41. The system of claim 40, wherein the algorithms are used to determine cycle threshold values and interpret the cycle threshold values to process the PCR test data thereby producing processed PCR test data.

42. The system of any one of claims 38-41, wherein the second cloud environment is configured to process the instrument telemetry data and log files to enable monitoring and proactive servicing of the instrument, using at least in part failure mode models, component wear and tear monitoring and predictions, or over-the-air updates to extend component life of the instrument, or any combination thereof.

43. The system of any one of claims 1-42, wherein the second cloud environment is configured to transmit software or firmware updates to the instrument or to the software for operating the instrument.Attorney Docket No. 61070-70860144. The system of any one of claims 1-43, wherein the software for operating the instrument is further configured to store the test data.

45. The system of claim 44, wherein the test data is stored on the software for operating the instrument for up to a number of test runs, wherein the number of test runs ranges from about 50 to about 1000.

46. The system of any one of claims 1-45, wherein each of the first cloud environment or the second cloud environment comprises one or more servers.

47. The system of any one of claims 1-46, wherein the first cloud environment and the second cloud environment are segregated from each other.

48. The system of any one of claims 1-47, wherein the first cloud environment and the second cloud environment are compartmentalized within an integrated cloud environment.

49. The system of any one of claims 1-48, wherein the system further comprises a third cloud environment, wherein the third cloud environment comprises manufacturing information for single-use test components used in the instrument, instrument manufacturing information, or any combination thereof.

50. The system of claim 49, wherein the manufacturing information for the single-use test components or the instrument manufacturing information is provided to the software for operating the instrument to track a manufacturing or recall status of the single-use test components or the instrument.

51. The system of claim 49 or 50, wherein the single-use test components comprise single-use discs used in a PCR instrument.

52. The system of claim 51, wherein a status of a single-use disc used in the PCR instrument is validated prior to performing a test on the PCR instrument by linking the single-use disc with a manufacturing or recall status of the single-use disc stored in the third cloud environment.

53. A method for secure patient data handling, the method comprising:Attorney Docket No. 61070-708601a) providing an instrument to test patient samples from a plurality of patients thereby producing test data, wherein no health record information or patient unique identifying information of any of the plurality of patients is received, stored, or accessed at or by the instrument;b) using an operating device with the instrument, wherein the operating device comprises software for operating the instrument, wherein the operating device is used to receive the test data from the instrument but not receive, store, or access the health record information of any of the plurality of patients, wherein the operating device is further used to interact with the instrument, a first cloud environment, and a second cloud environment;c) using the first cloud environment to store the health record information of the plurality of patients;d) using the second cloud environment to receive the test data from the operating device and process the test data thereby generating processed test data; ande) sending the processed test data from the second cloud environment to the first cloud environment, thereby linking the processed test data of each of the plurality of patients with the health record information of each of the plurality of patients.

54. A method of using an instrument to test patient samples, the method comprising:a) receiving one or more test samples by the instrument;b) using the instrument to obtain or collect test data from the one or more test samples; andc) producing one or more test results by the instrument,wherein the instrument receives the one or more test samples from a plurality of patients, and wherein no health record information of the plurality of patients is received, stored, or accessed at or by the instrument.

Images