Systems and methods for continuously monitoring blood analytes

Abstract

A system and method for continuously monitoring blood wherein the system comprises a sensor unit comprising an inline device fluidically connected a patient via a catheter; a fluidics line configured for passage of a flow of blood of the patient; and one or more sensors configured to measure a plurality of blood analytes from the flow of the blood; a computing unit comprising: a memory; and a processor comprising program instructions, wherein the program instructions, when executed, comprise: receiving blood analyte data corresponding to the plurality of blood analytes; integrating timestamps to the blood analyte data; determining one or more trends associated with the blood analyte data; comparing the one or more trends to predetermined thresholds; and determining a risk prediction of one or more medical complications based on whether the one or more trends meet a condition relative to the predetermined thresholds; and a display unit.

Description

Docket No. 0222-15WOPTSYSTEMS AND METHODS FOR CONTINUOUSLY MONITORING BLOOD ANALYTESFIELD OF THE DISCLOSURE

[0001] The present disclosure generally relates to systems, methods and devices for monitoring and assessing various blood analytes. More particularly, the present disclosure relates to systems, methods and devices for continuous monitoring of various blood analytes, providing real-time information on a patient's physiological condition.BACKGROUND

[0002] Critically ill patients admitted into specialized units within hospitals require intensive care and utmost attention by healthcare professionals to ensure that their medical needs are addressed, and their overall health is managed appropriately. Regardless of the complexity of their conditions, these patients need to be consistently monitored to detect any potential complications and identify any improvements. One of the key measures of a patient's condition is the analysis of blood parameters, especially blood gas levels, electrolyte levels, and blood cell count to provide insights on their respiratory conditions, metabolic functions, and any bleeding disorders, respectively.

[0003] The current standard of care for testing blood in patients with critical conditions involves the use of blood analyzers in point-of-care devices or traditional diagnostic lab testing centers. However, in order to collect samples for analysis, the current standard of care requires blood to be frequently drawn from patients, which can be as often as once every hour. As such, this may cause further discomfort for critically ill patients since it may cause several risks, including but not limited to bruising, inflammation, infections, and iatrogenic anemia.

[0004] There are also considerable time, costs and resources needed for testing as operating current standard of care devices often require specialized training, which can be a challenge if healthcare facilities have limited staff. The periodic requirement to draw blood from patients to monitor their conditions subsequently comes with the accumulation of biowastes which can pose significant health, environmental, and operational challenges. In addition, intermittent blood monitoring using the aforementioned methods can lead to missing critical and acute changes of the patient's condition, delaying appropriate interventions to be administered to theDocket No. 0222-15WOPT patient. It can also be especially challenging for neonates in critical care due to their limited blood volume as frequently drawing blood can impact their fragile health and development.

[0005] This background information is provided to reveal information believed by the applicant to be of possible relevance. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art or forms part of the general common knowledge in the relevant art.BRIEF SUMMARY

[0006] The following presents a simplified summary of the general inventive concept(s) described herein to provide a basic understanding of some aspects of the disclosure. This summary is not an extensive overview of the disclosure. It is not intended to restrict key or critical elements of the embodiments of the disclosure or delineate their scope beyond that which is explicitly or implicitly described by the following description and claims.

[0007] The present disclosures are directed to, in accordance with different embodiments, a device, system and method for continuously monitoring various blood analytes to analyze the current medical condition of a patient and predict risk of medical complications. Current devices and methods to monitor blood analytes involve frequently drawing blood from patients which comes with their own challenges. As such, there is a need to employ an advanced blood monitoring system and method to holistically measure a wide range of blood analytes without changing the patient's total blood volume to improve patient outcomes and supplement the current standard of care.

[0008] In accordance with one aspect, there is provided a system for continuously monitoring blood, the system comprising: an inline device fluidically connected to a catheter configured for intravenous insertion into a body of a patient; a fluidics line connected to the catheter and enclosed within the inline device, the fluidics line configured for passage of a flow of blood of the patient; and one or more sensors in the inline device or the catheter configured to measure a plurality of blood analytes from the flow of the blood; a computing unit operatively coupled to the sensor unit, the computing unit comprising: a memory; and a processor coupled to the memory comprising program instructions, wherein the program instructions, when executed, comprise: receiving blood analyte data corresponding to the plurality of blood analytes; integrating timestamps to the blood analyte data; determining one or more trends associated with the blood analyte data; comparing the one or more trends to predetermined thresholds; andDocket No. 0222-15WOPT determining a risk prediction of one or more medical complications based on whether the one or more trends meet a condition relative to the predetermined thresholds; and a display unit communicatively coupled to the computing unit, the display unit configured to display at least one of the blood analyte data and the risk prediction.

[0009] In some embodiments, the system further comprises a control unit configured to regulate the flow of the blood through the sensor unit.

[0010] In some embodiments, the sensor unit is first calibrated before the computing unit can execute the program instructions.

[0011] In some embodiments, the plurality of blood analytes comprises blood gases, electrolytes, metabolites, cellular evaluations, and temperature.

[0012] In some embodiments, the program instructions further comprise notifying a user of patient abnormalities using visual, auditory or haptic displays.

[0013] In some embodiments, the computing unit is integrated with electronic medical records.

[0014] In some embodiments, the predetermined thresholds are established by analyzing preexisting population data and historical data associated with the patient from the electronic medical records using a trained machine learning model.

[0015] In some embodiments, the condition is based on one or more deviations from the predetermined thresholds.

[0016] In accordance with another aspect, there is provided a method for continuously monitoring blood, the method comprising: coupling a sensor unit to a body of a patient, wherein the coupling comprises: inserting a catheter into the body of the patient intravenously, the catheter fluidically connected to an inline device, the inline device or the catheter comprising one or more sensors; and measuring, using the one or more sensors, a plurality of blood analytes from a flow of the blood of the patient through a fluidics line connected to the catheter and enclosed within the inline device, the fluidics line configured for passage of the flow of blood; processing blood analyte data corresponding to the plurality of blood analytes using a computing unit operatively coupled to the sensor unit, the computing unit comprising a processor and a memory comprising program instructions, when executed, comprise: receiving blood analyte data corresponding to the plurality of blood analytes; integrating timestamps to the blood analyte data; determining one or more trends associated with the blood analyte data;Docket No. 0222-15WOPT comparing the one or more trends to predetermined thresholds; and determining a risk prediction of one or more medical complications based on whether the one or more trends meet a condition relative to the predetermined thresholds; and displaying at least one of the blood analyte data and the risk prediction in a display unit, wherein the display unit is communicatively coupled to the computing unit.

[0017] In some embodiments, the method further comprises regulating, via a control unit, the flow of the blood through the sensor unit.

[0018] In some embodiments, the method further comprises calibrating the sensor unit before the computing unit can execute the program instructions.

[0019] In some embodiments, the plurality of blood analytes comprises blood gases, electrolytes, metabolites, cellular evaluations and temperature.

[0020] In some embodiments, the program instructions further comprise notifying a user of patient abnormalities using visual, auditory or haptic displays.

[0021] In some embodiments, the computing unit is integrated with electronic medical records.

[0022] In some embodiments, the predetermined thresholds are established by analyzing preexisting population data and historical data associated with the patient from the electronic medical records using a trained machine learning model.

[0023] In some embodiments, the condition is based on one or more deviations from the predetermined thresholds.

[0024] Other aspects, features and / or advantages will become more apparent upon reading of the following non-restrictive description of specific embodiments thereof, given by way of example only with reference to the accompanying drawings.BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Several embodiments of the present disclosure are provided, by way of examples only, with reference to the appended drawings, wherein:

[0026] FIG. 1 illustrates an exemplary patient utilizing an inline blood monitoring device, in accordance with one embodiment;

[0027] FIG. 2 illustrates a front section view of a sensor device, in accordance with one embodiment;Docket No. 0222-15WOPT

[0028] FIG. 3A, 3B, and 3C illustrate an enlarged front section view of different configurations of the fluidics and sensor portion of a sensor device, in accordance with one embodiment;

[0029] FIG. 4A illustrates a perspective view of an exemplary automated calibration kit, in accordance with one embodiment;

[0030] FIG. 4B illustrates a front view of an exemplary automated calibration kit, in accordance with one embodiment;

[0031] FIG. 4C illustrates a side view of an exemplary automated calibration kit, in accordance with one embodiment;

[0032] FIG. 5 illustrates a schematic diagram of a benchtop device with different components, in accordance with one embodiment;

[0033] FIG. 6 illustrates a schematic diagram of an inline blood monitoring system, in accordance with one embodiment;

[0034] FIG. 7 illustrates a schematic diagram of devices and a computer system used to continuously monitor blood analytes, in accordance with one embodiment;

[0035] FIG. 8 is a flowchart illustrating a workflow for processing blood analyte data by one or more processors, in accordance with one embodiment;

[0036] FIG. 9 is a flowchart illustrating a workflow for integrating electronic medical records into a blood monitoring system, in accordance with one embodiment;

[0037] FIG. 10 is a flowchart illustrating display modes of a dual user interface for a blood monitoring system, in accordance with one embodiment;

[0038] FIG. 11 is a flowchart illustrating different types of display systems for a blood monitoring system, in accordance with one embodiment; and

[0039] FIG. 12 is a flowchart illustrating a workflow for a calibration process for a sensor device using an automated calibration kit, in accordance with one embodiment.

[0040] Elements in the several drawings are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be emphasized relative to other elements for facilitating understanding of the various presently disclosed embodiments. Also, common, but well-understood elements that are useful or necessary in commercially feasible embodiments are often not depicted in order to facilitate a less obstructed view of these various embodiments of the present disclosure.Docket No. 0222-15WOPTDETAILED DESCRIPTION

[0041] Various implementations and aspects of the specification will be described with reference to details discussed below. The following description and drawings are illustrative of the specification and are not to be construed as limiting the specification. Numerous specific details are described to provide a thorough understanding of various implementations of the present specification. However, in certain instances, well-known or conventional details are not described in order to provide a concise discussion of implementations of the present specification.

[0042] Furthermore, numerous specific details are set forth in order to provide a thorough understanding of the implementations described herein. However, it will be understood by those skilled in the relevant arts that the implementations described herein may be practiced without these specific details. In other instances, well-known methods, procedures and components have not been described in detail so as not to obscure the implementations described herein.

[0043] In this specification, elements may be described as “configured to” perform one or more functions or “configured for” such functions. In general, an element that is configured to perform or configured for performing a function is enabled to perform the function, or is suitable for performing the function, or is adapted to perform the function, or is operable to perform the function, or is otherwise capable of performing the function.

[0044] When introducing elements of aspects of the disclosure or the examples thereof, the articles “a,” “an,” “the,” and “said” are intended to mean that there are one or more of the elements. The terms “comprising,” “including,” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements. The term “exemplary” is intended to mean “an example of.” The phrase “one or more of the following: A, B, and C” means “at least one of A and / or at least one of B and / or at least one of C.”

[0045] The devices, systems and methods disclosed herein can be utilized for continuously monitoring and assessing various blood analytes for patients admitted in hospitals, including, but not limited to critically ill patients who are in intensive care units and patients undergoing a surgical procedure. Embodiments can include a sensing and diagnostic device that utilizes one or more sensors, for example, on a catheter or an inline device that measures different types of blood analytes without changing a patient's total blood volume. Systems, methods and devices disclosed herein include sensors, such as biosensors that can be used to sense blood analytes. InDocket No. 0222-15WOPT some embodiments, sensors may include electrochemical sensors, which include but are not limited to potentiometric and amperometric sensors. Exemplary potentiometric sensors include ion-selective electrodes (ISE) and ion-sensitive field effect transistors (ISFET). By way of a non-limiting example, electrochemical sensors may include terminals that connect to active, counter, reference or pseudo-reference electrodes depending on the type of sensor being utilized. In some embodiments, sensors may include solid-state optical sensors such as optodes. By way of a non-limiting example, optical sensors may include a spectrometric unit that connects to solid-state sensing ends through optical fibers and contains light sources such as light-emitting diodes (LEDs), specific color filters, optical units such as lenses and mirrors, and light meters such as photodiodes.

[0046] Sensors can be of different types that include but are not limited to pH sensors, ion- sensitive / selective sensors, temperature sensors, lactate sensors, electrolyte sensors, light-based sensors such as absorbance, scattering, reflectance, or fluorescence sensors, semiconductor sensors, printed sensors, enzyme sensors, antibody sensors, gas sensors such as partial pressure of oxygen or carbon dioxide sensors, conductivity sensors, impedance sensors, pressure sensors, flow sensors, glucose sensors, hemoglobin sensors, flow cytometer, coulter counter, and hematocrit sensors.

[0047] Sensors may be connected in series or in parallel, and may be disposed sequentially, for example, along a length of a fluid channel for blood to pass.

[0048] In some embodiments, a microfluidic device may be used to control fluids such as calibration solution, flushing solution, or blood within the device. The microfluidic device may have some sensors disposed on it. The microfluidic device may have valves controlled by a blood montitoring system to exchange fluids in contact with the sensors. The microfluidic device may control the flow rate of the fluids on the sensors.

[0049] In some embodiments, the microfluidic device may have anticoagulant coating on the surface to reduce blood clotting, coagulation, or biofouling of the device.

[0050] In some embodiments, the microfluidic device may hold some reagents such as calibrators, dried reagents, liquid reagents, or quality control solutions within it. The microfluidic device may control intake of pharmaceuticals for the dosage, interval, or mixing rate into the patient blood flow.

[0051] In some embodiments, the microfluidic device may have embedded connections to other devices such as electrical contacts, wires, or optical fiber connectors.Docket No. 0222-15WOPT

[0052] In some embodiments, a temperature sensor may include a thermistor. In use, a thermistor may undergo changes in resistance correlated to changes in temperature. Thus, a temperature may be determined by determining a resistance of the thermistor, by exciting with current and measuring voltage (or vice versa).

[0053] A temperature sensor may be used to account for a number of artifacts and error sources in the biosignal measurements. A temperature sensor may be used to compensate or modulate signals from other sensors that are temperature dependent such as pH or gas partial pressure. A rise in temperature detected by temperature sensor can indicate an influx of new fluid, as blood tends to have higher temperatures relative to ambient temperatures.

[0054] An array of temperature sensors and a heating element may be used to measure fluid flow rate using the principles of thermal mass fluid transport.

[0055] In some embodiments, sensors may include a flow sensor such as a flowmeter to measure the volumetric or mass flow rate of blood intravascularly or in the blood monitoring device.

[0056] In some embodiments, sensors may include a pH sensor that is electrochemical in nature allowing blood analytes to be transduced into electrical signals that can then be measured, monitored and analyzed to determine any changes in blood composition, assessing a patient's overall health. A system of interdigitated electrodes (active, counter and reference) may be fabricated on a biocompatible substrate. The electrodes may be fabricated from biocompatible materials: gold, platinum, titanium and silver, and then later functionalized with an active polyaniline (PANI) polyaniline / polyurethane (PAIN / PU), polyurethane, polymer or other suitable layer. In an example, p-biosensors are 500pm x 500pm in size, allowing them to be placed on catheters to monitor changes in pH over time.

[0057] A pH sensor may be formed from a conducting polymer made from Aniline monomers. A sensitivity to pH levels of a suitable conducting polymer can allow for its use as a pH sensitive component in pH sensors.

[0058] A pH sensor may be calibrated and / or controlled by a potentiostat, in particular, an electronic device that controls the difference in potential and current of a 3-electrode system comprising of a working electrode (WE), a reference electrode (RE) as well as a counter electrode (CE). This electrical instrument has many applications that may be used to fabricate a pH sensor such as Cyclic Voltammetry (CV), Chronoamperometry and Chronopotentiometry.Docket No. 0222-15WOPT

[0059] A pH sensor may be configured to detect a pH value within a threshold or boundaries, or deviation from such boundaries.

[0060] In some embodiments, sensors may include optical sensors wherein fluorescent or chromogenic molecules embedded in a hydrogel specifically interacting with analytes of interest present in blood, creating varying fluorescence or absorbance signals corresponding to the concentration of analytes within the blood, including the partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), pH, sodium, potassium and ionized calcium concentrations.

[0061] An optical sensor may include selective fluorescent or chromogenic molecules (reporter molecules from here on) which will change its optical properties such as light absorption spectrum or light emission spectrum upon selectively interacting with the biomarkers of interest. The selectivity to the biomarkers would be created by either specific chemical structures on the reporter molecules, specific chemical environment around reporter molecules, selective chemical or biological carriers for the biomarkers, selectively permeable membrane(s) covering the sensor, selective surface modification of the sensor including but not limited to selective chemicals, enzymes, or antibodies, or a combination of some or all of above principles.

[0062] An optical sensor may include a solid-state sensing end that is composed of base material such as hydrogel and signal creating material such as the reporter molecules. The base material may protect the reporter molecules from physical and chemical damages such as drying, chemical bleaching, and / or photobleaching, and provides better physical properties that allows advantages such as better handling, storage, and stability. The base material may allow free exchange of water and biomarkers with the environment for better sensing. The reporter molecules may be embedded in the base material by covalent bonding, ionic bonding, Van-der- Waals bonding, entropic exclusion, physical trapping, or other physical phenomena.

[0063] An optical sensor may include specific wavelength light sources such as LEDs or lasers, or wide-spectrum light sources such as white light bulbs alone or in combination with wavelength selective components such as monochromators or chromatic filters. They may also be used in combination with polarizers to select for a specific polarity of the light.

[0064] An optical sensor may include a light meter that converts the intensity of light, or number of photons received, to electronic signal. The light meter may be photodiodes, photomultiplier tubes, charge-coupled devices, CMOS sensors or any other device that isDocket No. 0222-15WOPT capable of changing light energy to electrical energy. They may or may not be combined with light selective components such as chromatic filters, dichroic mirrors, monochromators, polarizers, or pinholes.

[0065] An optical sensor may include optical fibers to transmit the optical signals from one location to another, such as between the solid sensing end, light source, and light meter, or between sensor device and the benchtop device.

[0066] An optical sensor may include optical elements such as mirrors, lenses, prisms, or a combination of aforementioned elements to amplify the optical signal. The optical elements can be placed either within the solid-state sensing end, at the light sources, or at the light meters, or combination of the multiple locations listed.

[0067] An optical sensor may be configured specifically to detect a biomarker value within a threshold or boundaries, or with specific precision, sensitivity, and / or selectivity.

[0068] In some embodiments, sensors may be tailored to take electrical measurements. An exemplary sensor in this category involves measuring hematocrit and temperature based on changes of the electrical signal reading of the sensor that corresponds to the environmental characteristics of the blood surrounding the sensor surface.

[0069] In some embodiments, sensors may include light-based sensors, such as photoelectric sensors, utilizing a combination of light transmitters or sources and detectors in the ultraviolet to infrared spectrum to measure the fluid’s light absorption or transmission characteristics. Single-wavelength or multi -wavelength rays may be used.

[0070] Light-based sensors can include a combination of light transmitters and detectors in the ultraviolet to infrared spectrum and be used to measure a fluid's light absorption or transmission characteristics.

[0071] A light-based sensor may include multiple light sources and receivers. For instance, a single broadband light source may be used in combination with multiple band-specific photodiodes (e.g. red, green and blue). In this way, the absorption / transmission characteristics of the blood can be measured across as many bands as there are photodetectors present. Similarly, multiple light sources may be utilized in combination with a single broadband photodetector, whereby each light source is turned on successively and the transmitted light measured accordingly by the photodetector. Lastly, light sources and photodetectors may also utilize dynamic filters to allow the emission or detection of specific bands of light in lieu of multiple sources or photodetectors.Docket No. 0222-15WOPT

[0072] In some embodiments, an impedance sensor may be used to detect a sudden increase in impedance, which may be indicative of a presence and a quantity of non-homogenous substances and particles (e.g., blood clots, fibrin).

[0073] In some embodiments, an impedance sensor may be used to detect blood coagulation (typically characterized by a sudden increase in impedance, followed by a slower but sustained increase in impedance), and hence, the presence of blood clots and risk of channel blockage.

[0074] In some embodiments, an array of impedance sensors placed along the channel may be used to detect and track air bubbles, non-homogenous substances, and / or particles as they travel through the channel, using techniques described herein.

[0075] In some embodiments, a Coulter counter may be used to count the number of different blood cells, such as red blood cells, white blood cells, and platelets, per unit volume of the blood. The blood being supplied to the Coulter counter may or may not be diluted with additional fluid such as buffers. The blood cells may be analyzed further by a light-based sensor in combination, where the light-based sensor may use the light scattering properties of the blood cells to distinguish and analyze the cells further. The Coulter counter may distinguish between different species of the white blood cells.

[0076] A Coulter counter identifies and analyzes the blood cells using size estimation based on the electrical property changes when the blood cells are passing through an orifice. The Coulter counter may have a microfluidic device connected to supply the blood cells to ensure a single cell passage through the orifice for each measurement. The microfluidic device may or may not dilute the blood using microfluidic fluid control and volume metering. The orifice and the electrical circuitry composing the Coulter counter may be integrated into the microfluidic device as a portion of the microfluidic device. The microfluidic device may separate blood cells and other blood components within the device for the measurement in the Coulter counter or as the result of the Coulter counter measurement.

[0077] A Coulter counter may take a small volume of blood from the primary fluidic path for the analysis. The Coulter counter may or may not return the blood back to the patient. The Coulter counter may hemolyze some of the cells by chemical or mechanical hemolysis methods.

[0078] In some embodiments, a Coulter counter may use specifically labeled antibodies, such as fluorescently labeled antibodies, to help identify each type of blood cell.Docket No. 0222-15WOPT

[0079] In some embodiments, a Coulter counter may have its surfaces coated with anticoagulant to help against blood clotting, coagulation, or biofouling. The Coulter counter may have a fluid reservoir and a waste container connected to it to flush and maintain the system for repeated usage.

[0080] In some embodiments, an artificial intelligence algorithm may be used to process the data from the electrical, chemical, or optical signals collected by a Coulter counter and other sensors to identify the blood cells detected by the Coulter counter.

[0081] FIG. 1 illustrates an exemplary patient utilizing an inline blood monitoring device 102, in accordance with one embodiment. The inline blood monitoring device 102 is connected to a patient by a central venous catheter 114 that is configured to be surgically inserted into the patient 108. Following the insertion of the catheter 114 to the patient 108, whole blood is drawn automatically through a blood line, flows through the blood monitoring device for measurement, and is returned to the patient via the same catheter 114. The inline blood monitoring device 102 may comprise one or more sensors 104 configured to continuously monitor a plurality of blood analytes 106 from a patient 108. Blood from the patient continuously flows through a blood circuit 110 to circulate the blood from the patient 108, through the inline blood monitoring device 102, and back to the patient 108. The one or more sensors 104 of the inline blood monitoring device 102 may also be connected to a monitor 112 which may continuously process blood analyte data obtained from the one or more sensors 104. The connection can be established via different methods including but not limited to, circuit embedded within a circuit board hosting the sensors, wires and connectors between circuits or that may be configured to be embedded within the catheter's body or within at least one lumen designed to allow wires and connectors to run through them. The connection may also be established wirelessly by transmitting the data obtained in-vivo from biosensors via a transmitting system to a receiver placed outside the body.

[0082] In some embodiments, the one or more sensors 104 comprising single sensors or sensor arrays can be embedded along the wall of a catheter 114, inside dedicated lumens, or in a closed-loop, inline device 102, that enables the device to detect and monitor different blood analytes.

[0083] In some embodiments, multiple sensors 104 may be spaced apart along a length of the catheter 114. Multiple sensors placed along the catheter may allow for multiple regions to be sensed and spatial progression of blood analytes to be tracked. The catheter 114 may be formedDocket No. 0222-15WOPT of a tube having a hollow or solid body and made of medical grade materials, such as a suitable polymer. In some embodiments, the catheter may be a flexible substrate. In some embodiments, the catheter 114 may be formed of a material with low friction.

[0084] The catheter 114 may have different designs wherein the catheter 114 may be cylindrical, rectangular, flat, or T-shaped in cross-section and the catheter may have a single lumen or multiple lumens. The catheter 114 that has multiple lumens allows for more extensive functionality as medications can be administered simultaneously with blood being analyzed by the disclosed blood monitoring system.

[0085] In some embodiments, each of the one or more sensors 104 are independently in communication with a monitor 112 or DAQ.

[0086] The monitor 112 may have a screen allowing readouts to be directly observed on the device. The monitor 112 may also use various visual or audio queues such as graphs, small LEDs or alarm sounds to signal various events. The monitor 112 may be connected to a computer system or may be a part of a computer system as a display and / or user interface unit.

[0087] Data acquired by the monitor 112 or DAQ can also be communicated to a computer system via wired or wireless media to allow further analysis and visualization through a user interface such as a monitor. The data communicated may be processed, raw, or summarized.

[0088] In some embodiments, data collected by the monitor 112 or DAQ can be analyzed further by a computer system to identify trends associated with the development of different medical complications or response to different therapeutic agents, including but not limited to pharmaceutical drugs. This may be performed by evaluating single or multiple data sets acquired from one or more sensors over time to diagnose and determine the stage of development of medical complications.

[0089] Should one or more of the sensors demonstrate biological trends that are associated with blood disorders or other medical complications, an alarm signal or notification may be sent from the computer-based system to the monitor allowing health care providers to determine the appropriate medical action. By way of a non-limiting example, the alarm may comprise a visual display, auditory display or haptic display.

[0090] The term “blood parameters” as used herein may refer to biomarkers defined as molecules, substances, and chemical or physical properties that can be directly measured or detected as bio-signals in blood or can be calculated from one or more of the directly measured bio-signals. They include, but are not limited to oxygen concentration, oxygen saturation,Docket No. 0222-15WOPT partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), sodium, potassium, calcium, hematocrit, hemoglobin, white blood cells, sulfur dioxide, partial thromboplastin time, platelet count, glucose, pH, bicarbonate, magnesium, chloride, serum osmolarity, bilirubin, alkaline phosphatase, amylase, lipase and temperature.

[0091] In accordance with an embodiment of the present disclosure, various blood analytes are continuously monitored in an extracorporeal blood line. A blood monitoring device is connected to a patient by a central venous catheter that is configured to be surgically inserted into the patient. Following the insertion of the catheter to the patient, whole blood is drawn automatically through a blood line, flows through the blood monitoring device for measurement, and is returned to the patient via the same catheter. The blood monitoring system is configured to create a closed loop of blood flow wherein circulation is uninterrupted, seamlessly allowing the measurement of various blood analytes without altering or consuming any blood. As such, the blood monitoring system minimizes the risks of iatrogenic complications including infections, vascular injuries, and hemorrhages, among others.

[0092] In some embodiments, the continuous flow of blood through the device allows the device to report on the different measured blood analytes in real-time. As whole blood is continuously monitored, there is no requirement for sample removal from the system or even serum separation. The system is configured to ensure that it is biocompatible in terms of the materials used so as to not cause any unwanted, harmful reactions from the patient.

[0093] In some embodiments, the sensors take direct measurements of parameters including blood gases (e.g., partial pressure of oxygen, partial pressure of carbon dioxide, pH), electrolytes (e.g., sodium, potassium, ionized calcium), metabolites, cellular evaluations (CBC, hematocrit, etc.), temperature, and other analytes used in the diagnosis and monitoring of patients. However, the device is also capable of calculating further blood parameters based on the direct measurements using known equations. Exemplary blood parameters that can be calculated from the direct measurements include oxygen saturation, base excess, bicarbonate, and hemoglobin.

[0094] FIG. 2 illustrates a front section view of a sensor device 102, in accordance with one embodiment. The sensor device 102 may be disposable. In some embodiments, the disposable sensor device 102 for continuous blood monitoring comprises a catheter connector 202, fluidics and sensor portion 204, an extra reservoir 206 for blood, a pump 208, one or more batteries, 212 and a printed circuit board (PCB) 210. A sensor fluidics line 218 is configured to runDocket No. 0222-15WOPT through the catheter connector 202 and the fluidics and sensor portion 204. The fluidics and sensor portion 204 comprises one or more sensors 104 configured to detect a plurality of blood analytes. The PCB 210 is configured for communication, fluidics control and measurement. In some embodiments, the PCB 210 may comprise a DAQ, a wireless or wired communication board, and fluidic pump control. The sensor device 102 can be configured to be the size of a pen or marker with a wide body. In accordance with an embodiment, the dimensions of the sensor device may be approximately 1" x 1" x 5". In some embodiments, the sensor device 102 is configured to aspirate blood from the patient for blood analyte measurement through the fluidics and sensor portion 204 and push it back to the patient through the sensor fluidics line 218, allowing for bidirectional flow of blood. In some embodiments, the one or more sensors may be integrated within the catheter or placed in-situ. In some embodiments, the sensor fluidics line 218 may be connected to the catheter and / or enclosed within the sensor device 102, wherein the sensor fluidics line 218 is configured for passage of a flow of blood from a body of a patient. In some embodiments, the flow of blood may be continuous or intermittent.

[0095] FIG. 3A, 3B, and 3C illustrate enlarged front section views 302, 304, 306 of different configurations of the fluidics and sensor portion 204 of a sensor device 102, in accordance with one embodiment. The views 302, 304, 306 present orientations of the fluidics and sensor portion 204 after a 90° clockwise rotation in relation to the orientation of the fluidics and sensor portion 204 shown in FIG. 2. As illustrated, the sensors 104 in the fluidics and sensor portion 204 may have a linear configuration 302, branched configuration 304 or curved configuration 306, each housing one or more sensors 104.

[0096] In some embodiments, the pump may be a linear or peristaltic pump, to allow the blood to continuously flow through the system. The pump ensures that the blood flows seamlessly for the sensors to accurately measure the relevant analytes for further processing. The inline blood monitoring device may also be connected to a fluid supply such as a saline solution to perform therapeutic functions such as hemodialysis and the delivery of therapeutic agents, including but not limited to pharmaceutical drugs. The rate of blood flow through the device may also be controlled by the blood pump or other control units in order to reach an optimal level at which the sensors can take accurate measurements of different blood analytes. The length and volume of the blood line used in the system may also vary based on the type of application. For example, neonates require a smaller blood line compared to that of an adult. Moreover, there may be various configurations in which the central venous catheter and theDocket No. 0222-15WOPT blood line are connected, for example, through permanent fusion or through adapters and the like to add more flexibility to the system. The system may be calibrated manually by a healthcare professional or configured to be automatically calibrated in predetermined time intervals.

[0097] FIG. 4A illustrates a perspective view of an exemplary automated calibration kit 402, in accordance with one embodiment. The automated calibration kit 402 comprises a body 404 with a base 406 and a top portion 408, wherein the base 406 is configured to have a flat surface and the top portion 408 is configured to be angled relative to the flat surface. The body 404 comprises a plurality of sensor device holders 410 vertically extending towards the base 406 configured to docket a sensor device 102 within each of the plurality of sensor device holders 410. The top portion 408 comprises a plurality of slots 412 corresponding to the plurality of sensor device holders 410 configured for receiving the one or more sensor devices 102. The front portion of the base 406 comprises a system status indicator 414 and a power indicator 416 or a power button.

[0098] FIG. 4B illustrates a front view of an exemplary automated calibration kit 402, in accordance with one embodiment. Within the body 404 of the automated calibration kit 402 are a plurality of grooves 418 corresponding to each of the plurality of sensor device holders 410. Each of the plurality of sensor device holders 410 has a depth that is less than the length of a sensor device 102 such that when the sensor device 102 is inserted into each sensor device holder 410, a portion of the sensor device 102 remains exposed above the body 404, allowing a user to access the sensor device 102. Furthermore, the base 406 comprises a pump 420 configured to drive calibration fluid flow and a three-way valve 422 that directs fluid flow to and from each sensor device 102 in the body 404 of the automated calibration kit 402, fluid flow from one or more reservoirs 424, and fluid flow to a waste container 426.

[0099] FIG. 4C illustrates a side view of an exemplary automated calibration kit 402, in accordance with one embodiment. The side view of the automated calibration kit 402 more clearly depicts the different depths of the plurality of sensor device holders 410. In this embodiment, the one or more fluid reservoirs 424 are placed towards the bottom front side of the body 404, while the waste reservoir 426 is placed towards the bottom back side of the body 404.

[0100] The one or more sensor devices 102 can be calibrated on the automated calibration kit 402, which can also be used as a docketing device for the one or more sensor devices 102.Docket No. 0222-15WOPTRegardless of the number of sensor devices 102 loaded into the automated calibration kit 402, once activated, it initiates calibration and prepares each sensor device 102 for use. An exemplary set up involves the automated calibration kit 402 preparing each sensor device 102 automatically every 8 hours and notifying the user through a visual or auditory signal to replace the used sensor devices on the system with calibrated sensor devices. A method of using the automated calibration kit 402 is described in FIG. 12.

[0101] FIG. 5 illustrates a schematic diagram of a benchtop device 502 with different components, in accordance with one embodiment. The benchtop device 502 for continuous blood monitoring may comprise at least one of a sensor control module 504, data analysis module 506, communication module 508, data storage module, device control module, user I / O module, power module 510, DAQ module, pump 512, fluid control module, sensor module 514, and / or a temperature control module. In an exemplary embodiment, the benchtop device 502 is connected to tubing with a loop 516 where one part of the loop 516 is joined at a catheter connector 518 while the loop 516 goes through the sensor module 514. One or more tubing extensions 520 from the loop are configured for fluid flow from a calibration port 522 to a calibration outlet 524. The calibration port 522 is configured to access calibration fluid from a calibration reservoir 526, while the calibration outlet 524 is configured for draining used calibration fluid to a waste container or waste reservoir 528. The one or more tubing extensions 520 are connected to the loop 516 via a valve 530 at each connection point. The sensor module 514 may be placed in between the valves 530 inline with the loop 516. The sensor module 514 and the loop 516 tubing may be disposable and replaceable. The benchtop device 502 may also be connected to external modules such as reagent packs or a liquid waste reservoir for used calibration wash solutions. In accordance with an embodiment, the benchtop device 502 may be approximately the size of an 8" x 5" x 4" box.

[0102] In some embodiments, the sensor device 102 may have wireless or wired connection with the benchtop device 502, which comprises a computer system that may include sensor device control module, data analysis module, communication module, data storage module, user I / O module, power module, and a monitor / user interface.

[0103] In some embodiments, a disposable sensor device 102 for continuous blood monitoring comprises an intravascular sensor array that is inserted into patient via catheters. The sensor device would have wireless or wired connection with a benchtop device, which comprises a computer system that may include sensor control module, data analysis module, communicationDocket No. 0222-15WOPT module, data storage module, device control module, user I / O module, power module, DAQ module.

[0104] FIG. 6 illustrates a plurality of components of an inline blood monitoring system 602, in accordance with one embodiment. The inline blood monitoring system 602 may comprise a fluidics component 604, FW / SW component 606, sensor component 608, and hardware component 610. The fluidics component 604 may comprise units for sample control 612, calibrator control 614, and actuation control 616. The FW / SW component 606 may comprise units for sensor communication 618, data analysis 620, data management 622, user interface 624, and device control 626. The sensor component 608 may comprise units for the measurement of blood gases, electrolytes, conductivity signals at block 628, and temperature measurement at block 630, as well as the detection of abnormalities at block 632. The hardware component 610 may comprise, by way of a non-limiting example, a device circuit board 634, device housing 636, sample in-take / exit 638, control panel 640, power supply 642, and peripherals 644. The different units within each component of the inline blood monitoring system 602 may be communicatively coupled with each other.

[0105] FIG. 7 is a schematic diagram illustrating an exemplary computer system 710 with which aspects of the disclosure may be implemented. According to an embodiment, blood flows from a patient 708 to a sensor device 704 and back to the patient 740 in a continuous manner. During the continuous cycle of blood when in data acquisition mode, blood flowing from the patient is sent to a sensor device 702, where it flows over one or more sensor elements in the sensor device 702. Data pertaining to blood analytes in the blood is measured by the sensor elements and sent to a processor 714 of the computer system 710, where the patient data is processed. The sensor device 702 may be in operable communication with a benchtop device 734 through a wired or wireless connection where patient data may be transferred from the sensor device to the benchtop device 736 or from the benchtop device to the sensor device 738.

[0106] The computer system 710 may be implemented using hardware or a combination of software and hardware, either in a dedicated server, integrated into another entity, or distributed across multiple entities. The computer system 710, or aspects of it, may be integral to the sensor device 702 and / or benchtop device 734, or separate from it. The sensor device 702 may communicate with the computer system 710 via a communication mechanism 712 wirelessly over a network, or via a wired communication mechanism. In a similar manner, the benchtop device 734 may communicate with the computer system 710 via a communicationDocket No. 0222-15WOPT mechanism 736 over a network, or via wired communication mechanism. Computer system 710 includes a bus 728 or other communication mechanism for communicating information, and a processor 714 coupled with bus 728 for processing information. By way of example, the computer system 710 may be implemented with one or more processors 714. Processor 714 may reside in the sensor device 702, benchtop device 734, in the computer system 710, or both. Data may be pre-processed in the sensor device 702, for example by correction of data based on on-site conditions, and then sent to a computer system 710 for more rigorous processing. Processor 714 may be a general -purpose microprocessor, a microcontroller, a Digital Signal Processor (DSP), an Application Specific Integrated Circuit (ASIC), a Field Programmable Gate Array (FPGA), a Programmable Logic Device (PLD), a controller, a state machine, gated logic, discrete hardware components, or any other suitable entity that can perform calculations or other manipulations of information.

[0107] Computer system 710 can include, in addition to hardware, code that creates an execution environment for the computer program in question, e.g., code that constitutes processor firmware, a protocol stack, a database management system, an operating system, or a combination of one or more of them stored in an included memory 716, such as a Random Access Memory (RAM), a flash memory, a Read Only Memory (ROM), a Programmable Read- Only Memory (PROM), an Erasable PROM (EPROM), registers, a hard disk, a removable disk, a CD-ROM, a DVD, or any other suitable storage device, coupled to bus 728 for storing information and instructions to be executed by processor 714. The processor 714 and the memory 716 can be supplemented by, or incorporated in, special purpose logic circuitry. The sensor device 702 and the benchtop device 734 may have their own memory 716 for storing data. The memory 716 may be in a separate computer system 710. The memory 716 may comprise cloud data storage 718.

[0108] The instructions may be stored in the memory 716 and implemented in one or more computer program products, i.e., one or more modules of computer program instructions encoded on a computer readable medium for execution by, or to control the operation of, the computer system 710, and according to any method well-known to those of skill in the art, including, but not limited to, computer languages such as data-oriented languages (e.g., SQL, dBase), system languages (e.g., C, Objective-C, C++, Assembly), architectural languages (e.g., Java, .NET), and application languages (e.g., PHP, Ruby, Perl, Python). Instructions may also be implemented in computer languages such as array languages, aspect-oriented languages,Docket No. 0222-15WOPT assembly languages, authoring languages, command line interface languages, compiled languages, concurrent languages, curly-bracket languages, dataflow languages, data- structured languages, declarative languages, esoteric languages, extension languages, fourth-generation languages, functional languages, interactive mode languages, interpreted languages, iterative languages, list-based languages, little languages, logic-based languages, machine languages, macro languages, metaprogramming languages, multiparadigm languages, numerical analysis, non-English-based languages, object-oriented class-based languages, object-oriented prototypebased languages, off-side rule languages, procedural languages, reflective languages, rulebased languages, scripting languages, stack-based languages, synchronous languages, syntax handling languages, visual languages, wirth languages, and xml-based languages. Memory 616 may also be used for storing temporary variable or other intermediate information during execution of instructions to be executed by processor 714.

[0109] A computer program as discussed herein does not necessarily correspond to a file in a file system. A program can be stored in a portion of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, subprograms, or portions of code). A computer program can be deployed to be executed on one computer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network. The processes and logic flows described in this specification can be performed by one or more programmable processors executing one or more computer programs to perform functions by operating on input data and generating output.

[0110] Computer system 710 may further include data storage 718 such as a magnetic disk or optical disk, coupled to bus 728 for storing information and instructions. Computer system 710 may be coupled via input / output module 720 to various devices, including a display device 730, such as a computer monitor. The computer system 710 may be connected to the display device 730 via a communication mechanism 732 over a network, or via wired communication mechanism. The input / output module 720 can be any input / output module. Exemplary input / output modules 720 include data ports such as USB ports. The input / output module 720 is configured to connect to a communications module 722. Exemplary communications modules 722 include networking interface cards, such as Ethernet cards and modems. In certain aspects, the input / output module 720 is configured to connect to a plurality of devices, such as an inputDocket No. 0222-15WOPT device 724 and / or an output device 726. Exemplary input devices 724 include a keyboard and a pointing device, e.g., a mouse or a trackball, by which a user can provide input to the computer system 710, Other kinds of input devices 724 can be used to provide for interaction with a user as well, such as a tactile input device, visual input device, audio input device, or braincomputer interface device. For example, feedback provided to the user can be any form of sensory feedback, e.g., visual feedback, auditory feedback, or tactile feedback, and input from the user can be received in any form, including acoustic, speech, or tactile input. Exemplary output devices 726 include display devices such as an LCD (liquid crystal display) monitor, for displaying information to the user.

[0111] According to one aspect of the present disclosure, the methods for processing blood analyte data and detected by a sensor device 702 and benchtop device 734, described herein, can be implemented using a computer system 710 in response to processor 714 executing one or more sequences of one or more instructions contained in memory 716. Such instructions may be read into memory 716 from another machine-readable medium, such as a data storage device 718. Execution of the sequences of instructions contained in the main memory 716 causes processor 714 to perform the process steps described herein. One or more processors in a multiprocessing arrangement may also be employed to execute the sequences of instructions contained in memory 716. In alternative aspects, hard-wired circuitry may be used in place of or in combination with software instructions to implement various aspects of the present disclosure. Thus, aspects of the present disclosure are not limited to any specific combination of hardware circuitry and software.

[0112] FIG. 8 is a flowchart illustrating a workflow for processing blood analyte data by one or more processors 714, in accordance with one embodiment. The disclosed blood monitoring system allows for one or more paths of data flow to predict any risk of medical complications. A first path 802 may be associated with processing data extracted from an inline blood monitoring device with one or more sensors 104. A second path 804 may be associated with processing preexisting population data and patient historical data. The preexisting population data and patient historical data may comprise demographics, weight, sex, age, medical records, surgical history, and the like. The first path 802 and second path 804 may be initiated simultaneously or asynchronously. Should the first path 802 and the second path 804 be initiated asynchronously, the processed data may be stored in a memory that can be accessed by one or more processors 714 at any time when a risk prediction is needed for a given patient.Docket No. 0222-15WOPT

[0113] The first path 802 begins with patient blood being in direct contact with each of the one or more sensors 104 from a sensor device 102 as patient blood flows through them. The one or more sensors 104 are configured to record continuous raw signals of a plurality of blood parameters, wherein the plurality of blood parameters are transformed into a plurality of temporal blood parameters to integrate different timestamps associated with each data point. The plurality of temporal blood parameters is then used as a basis for determining a temporal trend of blood parameters.

[0114] The second path 804 begins with gathering preexisting population data and patient historical data before analyzing the data gathered to determine thresholds for indicating medical complications. The thresholds for indicating complications will be predetermined by either a manufacturer, manual user input, or an automated algorithm that may be trained using patient's historical data and / or preexisting population data. In addition to determining thresholds, risk prediction criteria may be determined from the analysis as well. The blood monitoring system will utilize both the measured value of the blood parameters and / or the trend of the blood parameters from the first path 802 and compare them with the predetermined thresholds and risk prediction criteria from the second path 804 to assess a patient’s health condition and determine any risk of medical complications. If a concerning level of risk is detected, users (i.e., clinicians) are alerted. If a concerning level of risk is predicted, previously determined risk predictions are updated. Regardless of the detected or predicted level of risk, the recorded blood parameters are displayed on a display device 730.

[0115] In some embodiments, the display device 730 may have an alert or alarm function that notifies the user about patient abnormalities using visual, auditory, or haptic displays. In some embodiments, risk information may be displayed in an internet-assisted application that may be displayed in smartphones, tablets, or computers, with visuals and functionalities that may or may not be the same as a dedicated display and may or may not run on a dedicated application program or internet browsers. In some embodiments, users may input data into the blood monitoring system for patient management, sensor calibration, system authorization, and / or treatment management such as ventilator management.

[0116] In some embodiments, artificial intelligence-aided algorithms are used to process, analyze and report direct and calculated measurements of blood analytes from a wide range of sensors. These may act as a means to detect and predict risk regarding a patient's current medical condition. Furthermore, using the measured sensory data, these algorithms may also 1Docket No. 0222-15WOPT make risk predictions of various medical complications, such as sepsis, along with an associated confidence level. The direct measurements, calculated measurements, and predicted risks may be displayed on a patient monitor for healthcare providers to review the records, track the condition of the patient in real-time, and make an informed decision for the patient regarding any next steps including taking specific medications, treatments, or other interventions to improve their overall health. Furthermore, the ability of the algorithm to predict medical complications based on the analytes monitored better supports physicians in terms of patient management as they would spend less time manually analyzing the measured patient data. As such, embodiments of the device, system and method disclosed herein may identify physiological differences between a patient's current medical condition and precursors to any potential medical complications that may arise in the future.

[0117] There are particular clinical ranges in which different blood analytes should fall under to be considered normal. The required values set by CLIA (Clinical Laboratory Improvement Amendments), clinical normal ranges (Tietz, 2018), and target measuring ranges for the disclosed system are found in Table 1. Any significant deviation from these normal ranges may likely indicate that a patient requires medical attention.

[0118] Table 1. Normal Ranges for Exemplary Blood Analytes.RequiredTargetPerformanc MeasuriAcronym e (CLIA, Clinical Normal TargetAnalyte ng (Commo 2024), Range (Tietz, MeasurinName Precisio n Units) Target 2018) g Range n (CV orValue + / - SD) value8-24 mmHg: birth;33-75 mmHg: 5-10Oxygen pO? 15 mmHg or 10-700 mins after birth; 31- 1.5-5%Partial (mmHg or 15% (or 800)85 mmHg: 30 mins CVPressure kPa) (Greater) mmHg after birth; 55-80 mmHg: 1 hr afterDocket No. 0222-15WOPT birth; 54-95 mmHg:Id after birth; 83- 108 mmHg: 2d after birth to 60 yrOxygen 40-90% newborn; sO2(%) N / A 30-100% 0.3% CVSaturation 94-98% thereafterCarbon 1-855-20%: 0-14d; 10-Dioxide mmol / L tCO224%: 15d-lyr; 14-(Bicarbon bicarbona(mEq / L or 20% 24%: l-5yr; 17-ate) te; 5-50 mmol / L) 26%: 5-6yr; 19- Concentra mmol / L24%: 6-79yr tion tCO227-40 mmHg:Carbon newborn; 27-41 pCO2Dioxide 5mmHg or mmHg: infant; 35- 5-150 1.5-3%(mmHg orPartial 8% (Greater) 48 mmHg: adult M; mmHg CV kPa)Pressure 32-45 mmHg: adult7.35-7.50: premature, 48hr;7.11-7.36: full term, birth; 7.09-7.30: 5- 10 mins after birth; pH pH 0.04 6.5-8.0 0.02 pH7.01-7.38: 30 mins after birth; 7.26-7.49: 1 hr after birth; 7.29-7.45: Id after birth; 7.35-Docket No. 0222-15WOPT7.45, children and adults3.0-6.0 mmol / L: premature, 48hr;3.7-5.9 mmol / L:K (mEq / L newborn; 4.1-5.3 2.0-9.0 0.04Potassium or 0.3 mmol / L mmol / L: infant; mmol / L mmol / L mmol / L) 3.9-4.6 mmol / L: 3-5 yr; 3.8-4.9 mmol / L:6-79 yr128-148 mmol / L: premature, 48hrs;133-146 mmol / L:Na newborn; 139-146 100-200 0.5Sodium (mEq / L or 4 mmol / L mmol / L: infant; mmol / L mmol / L mmol / L) 135-142 mmol / L: 3-5 yr; 136-143 mmol / L: 16-49 yr100-107%: 3-5 yr;Cl 101-107%: 6-11 yr;65-140Chloride (mEq / L or 5% 100-107%: 12-29 1% CV mmol / L mmol / L) yr; 102-108%: 30-79 yr34-42%: 3-7 yr; 35-Hematocr 43%: 8-11 yr; 38-Hct (%) 4% 10-75% 1.5% CV it 47%: 12-15 yr M;40-50%: 16-79 yrDocket No. 0222-15WOPTM; 35-43%: 12-79 yr FCa2+Calcium 0.25-2.5(mg / dL or N / A 1.15-1.33 mmol / L 1.5% CV(ionized) mmol / L mmol / L)

[0119] FIG. 9 is a flowchart illustrating a workflow for integrating electronic medical records into a blood monitoring system, in accordance with one embodiment. A patient profile is created at block 902 for a plurality of patients in electronic medical records 904 to associate medical data with each patient of the plurality of patients. Along with other types of medical data, treatment recordings 922 are stored in electronic medical records 904 as well. Data is retrieved at block 906 from the electronic medical records 904 and subsequently converted at block 908 to produce a comprehensive patient profile 910. The comprehensive patient profile 910 and collected data from a sensor device 932 are then used to predict risk at block 912 and produce a complication risk score at block 916. The comprehensive patient profile 910 is also used as the source of data for patient data panels 914 in a comprehensive central display 918 shown in a display device. Treatment timepoint markings 920 from the treatment recordings 922 may be used to inform the measured sensor-derived data trends 924. Together with the complication risk score 916 and measured sensor-derived data trends 924, the patient data panels 914 are updated in the central display.

[0120] In some embodiments, the blood monitoring system may relay risk information to the central display, which allows for multiple patients to be monitored at the same time on a single display. In some embodiments, the blood monitoring system may relay the collected data from the sensor device at a set time interval at block 926 to an electronic medical record system to record the results automatically in the electronic medical records 904. The blood monitoring system may alternatively relay the collected data from the sensor device to an electronic medical record system to record the results automatically in the electronic medical records 904 at block 928 when the collected data from the sensor device meets a pre-determined condition 930. Iln some embodiments, the blood monitoring system may retrieve a plurality of patient data from the electronic medical record system associated with the patient for a more accurate prediction of health conditions. Using the electronic medical record system associated with theDocket No. 0222-15WOPT patient would also involve having all electronic medical records 904 associated with the patient in a single display or application, providing a more comprehensive view of patient data, associated with the patient in a single display or application, providing a more comprehensive view of patient data.

[0121] FIG. 10 is a flowchart illustrating display modes of a dual user interface for a blood monitoring system, in accordance with one embodiment. A virtual switch 1002 and user toggle 1004 may be used to navigate different display modes 1006 of the dual user interface. Users may opt to choose a live display mode 1032 (i.e., a concise view of patient data) or a monitoring display mode 1034 (i.e., a more comprehensive view of patient data). The live display mode 1002 shows live numerical blood parameters 1014 wherein the following features are turned off: risk prediction at block 1008, comprehensive display at block 1010, and time course trends at block 1012. The live display mode may be configured with a timer such that the timer starts 1016 once the live display mode is selected. Once the timer ends 1018, a user may be prompted to extend the time 1020 by resetting the timer 1022. Should the timer be reset, the display will continue to show the live display 1032 until the timer ends 1018 and prompts the user for an additional extension of time 1020. Conversely, should the timer not be reset, the display switches to the monitoring display mode 1034 wherein the following features are turned on: risk prediction at block 1024, comprehensive display at block 1026, and time course trends at block 1028 for continuous monitoring 1030 of medical complication risk for a given patient.

[0122] FIG. 11 is a flowchart illustrating different types of display systems for a blood monitoring system, in accordance with one embodiment. Full user interface functions 1102 may be accessed in an on-device display 1104. If patient data is accessed via a mobile application 1108 or web application 1110, the full user interface functions are available as well, but patient personal data is anonymized 1106 for confidentiality purposes. For a central system monitor 1116, the display system may solely show trend monitoring and alarms 1112 and show patient data relating to all active patients within a given unit 1114 of a hospital or other healthcare institute.

[0123] FIG. 12 is a flowchart illustrating a workflow for a calibration process for a sensor device 102 using an automated calibration kit 402, in accordance with one embodiment. Before initiating calibration, user input 1202 is required to turn on the automated calibration kit 402. The user must also check the fluid reservoirs 424 and waste reservoir 426 at block 1204, andDocket No. 0222-15WOPT identify the one or more sensor devices 102 to be calibrated at step 1212. To prepare the sensor device units for calibration, they need to be powered on as shown in block 1214 before running an electronics check-up at block 1216 and initiating sensor unit fluid controls at block 1224. Once the automated calibration device with the docketed sensor device is turned on, the calibrator pump is started by the user as shown in step 1206. Having the pump started leads to a first washing step at block 1208 which involves washing a calibrator fluid path and sensor fluidics portion of each sensor device with water. Following the first washing step at block 1208 is a first calibration step at block 1210 which involves washing the calibration fluid path with a first calibrator fluid and measuring a first calibration point at block 1220. After the first calibration point 1222 is determined, the second washing step at block 1226 begins which involves washing a calibrator fluid path and sensor fluidics portion of each sensor device with water. Following the second washing step at block 1226 is a second calibration step at block 1230 which involves washing the calibration fluid path with a second calibrator fluid and measuring a second calibration point at block 1232. Once the first calibration point 1222 and the second calibration point 1234 are measured, a calibration curve is determined at block 1228 which indicates whether the sensor device is calibrated and ready for use within the blood monitoring system as shown in block 1236.

[0124] In some embodiments, more than two sequential washing and calibration steps may be conducted to calibrate the one or more sensor devices 102. After the last calibration step, the calibrator fluid path and the sensor fluidics portion of the sensor device 102 are washed once more with water at block 1240 before the calibrator unit returns to standby as shown in block 1242. The fluid reservoirs 424 and waste reservoir 426 may also need to be checked as needed in case the fluid reservoirs 424 need to be refilled, or the waste reservoir 426 needs to be emptied.

[0125] Embodiments of the subject matter described in this specification can be implemented in a computing system that includes: a front end component (e.g., a client computer having a graphical user interface or a Web browser through which a user can interact with an implementation of the subject matter described herein); or a middleware component (e.g., an application server); or a back end component (e.g. a data server); or any combination of one or more such back end, middleware, or front end components. The components of the system can be interconnected by any form or medium of digital data communication, e.g., aDocket No. 0222-15WOPT communication network. Non-limiting examples of communication networks include a local area network ("LAN") and a wide area network ("WAN").

[0126] The computing system can include clients and servers. A client and server are generally remote from each other and typically interact through a communication network. The relationship between client and server arises by virtue of computer programs running on the respective computers and having a client-server relationship with each other. The computing system can be, for example, and without limitation, a desktop computer, laptop computer, or tablet computer.

[0127] In some embodiments, different machine-learning algorithms or techniques may be used, alone or in combination. These may include, for example, deep learning architectures such as Deep Belief Network (DBN), Stacked Auto Encoder (SAE), Convolutional Neural Network (CNN) or Recurrent Neural Network (RNN) may be used. Other examples include, without limitation, Restricted Boltzmann machines (RBM), Social Restricted Boltzmann Machines (SRBM), Fuzzy Restricted Boltzmann Machines (FRBM), TTRBM models of Deep Belief Networks (DBN) or similar approaches could be used; AE, FAE, GAE, DAE, BAE models of Statistically Adjusted End Use (SAE) models could be used; models such as Al exNet, ResNet, Inception, VGG16, ECNN models of CNN may be used; Bidirectional Recurrent Neural Networks (BiRNN), Long Short-Term Memory (LSTM) networks, Gate Recurrent Unit (GRU) of RNN may also be used. Additional techniques specific to time-series modelling may be used, including, but not limited to, dynamic time warping, change point detection, and Autoregressive Integrated Moving Average (ARIMA).

[0128] The present disclosure includes systems having processors to provide various functionality to process information, and to determine results based on inputs. Generally, the processing may be achieved with a combination of hardware and software elements. The hardware aspects may include combinations of operatively coupled hardware components including microprocessors, logical circuitry, communication / networking ports, digital filters, memory, or logical circuitry. The processors may be adapted to perform operations specified by a computer-executable code, which may be stored on a computer readable medium.

[0129] The steps of the methods described herein may be achieved via an appropriate programmable processing device that executes software, or stored instructions. In general, physical processors and / or machines employed by embodiments of the present disclosure for any processing or evaluation may include one or more networked or non-networked generalDocket No. 0222-15WOPT purpose computer systems, microprocessors, field programmable gate arrays (FPGA's), digital signal processors (DSP's), micro-controllers, and the like, programmed according to the teachings of the exemplary embodiments discussed above and appreciated by those skilled in the computer and software arts. Appropriate software can be readily prepared by programmers of ordinary skill based on the teachings of the exemplary embodiments, as is appreciated by those skilled in the software arts. In addition, the devices and subsystems of the exemplary embodiments can be implemented by the preparation of application-specific integrated circuits, as is appreciated by those skilled in the electrical arts. Thus, the exemplary embodiments are not limited to any specific combination of hardware circuitry and / or software.

[0130] Stored on any one or a combination of computer readable media, the exemplary embodiments of the present disclosure may include software for controlling the devices and subsystems of the exemplary embodiments, for driving the devices and subsystems of the exemplary embodiments, for processing data and signals, for enabling the devices and subsystems of the exemplary embodiments to interact with a human user or the like. Such software can include, but is not limited to, device drivers, firmware, operating systems, development tools, applications software, and the like. Such computer-readable media further can include the computer program product of an embodiment of the present disclosure for preforming all or a portion (if processing is distributed) of the processing performed in implementations. Computer code devices of the exemplary embodiments of the present disclosure can include any suitable interpretable or executable code mechanism, including but not limited to scripts, interpretable programs, dynamic link libraries (DLLs), complete executable programs and the like. Common forms of computer-readable media may include, for example, magnetic disks, flash memory, RAM, a PROM, an EPROM, a FLASH-EPROM, or any other suitable memory chip or medium from which a computer or processor can read.

[0131] While the present disclosure describes various embodiments for illustrative purposes, such description is not intended to be limited to such embodiments. On the contrary, the applicant's teachings described and illustrated herein encompass various alternatives, modifications, and equivalents, without departing form the embodiments, the general scope of which is defined in the appended claims. Information as herein shown and described in detail is fully capable of attaining the above-described object of the present disclosure, the presently preferred embodiment of the present disclosure, and is thus, representative of the subject matter which is broadly contemplated by the present disclosure.

Claims

Docket No. 0222-15WOPTCLAIMSWhat is claimed is:

1. A system for continuously monitoring blood, the system comprising: a sensor unit comprising: an inline device fluidically connected to a catheter configured for intravenous insertion into a body of a patient; a fluidics line connected to the catheter and enclosed within the inline device, the fluidics line configured for passage of a flow of blood of the patient; and one or more sensors in the inline device or the catheter configured to measure a plurality of blood analytes from the flow of the blood; a computing unit operatively coupled to the sensor unit, the computing unit comprising: a memory; and a processor coupled to the memory comprising program instructions, wherein the program instructions, when executed, comprise: receiving blood analyte data corresponding to the plurality of blood analytes; integrating timestamps to the blood analyte data; determining one or more trends associated with the blood analyte data; comparing the one or more trends to predetermined thresholds; and determining a risk prediction of one or more medical complications based on whether the one or more trends meet a condition relative to the predetermined thresholds; and a display unit communicatively coupled to the computing unit, the display unit configured to display at least one of the blood analyte data and the risk prediction.Docket No. 0222-15WOPT2. The system of claim 1, further comprising a control unit configured to regulate the flow of the blood through the sensor unit.

3. The system of claim 1, wherein the sensor unit is first calibrated before the computing unit can execute the program instructions.

4. The system of claim 1, wherein the plurality of blood analytes comprises blood gases, electrolytes, metabolites, cellular evaluations, and temperature.

5. The system of claim 1, wherein the program instructions further comprise notifying a user of patient abnormalities using visual, auditory or haptic displays.

6. The system of claim 1, wherein the computing unit is integrated with electronic medical records.

7. The system of claim 6, wherein the predetermined thresholds are established by analyzing preexisting population data and historical data associated with the patient from the electronic medical records using a trained machine learning model.

8. The system of claim 1, wherein the condition is based on one or more deviations from the predetermined thresholds.

9. A method for continuously monitoring blood, the method comprising: coupling a sensor unit to a body of a patient, wherein the coupling comprises: inserting a catheter into the body of the patient intravenously, the catheter fluidically connected to an inline device, the inline device or the catheter comprising one or more sensors; and measuring, using the one or more sensors, a plurality of blood analytes from a flow of the blood of the patient through a fluidics line connected to the catheter and enclosed within the inline device, the fluidics line configured for passage of the flow of blood; processing blood analyte data corresponding to the plurality of blood analytes using a computing unit operatively coupled to the sensor unit, the computing unit comprising a processor and a memory comprising program instructions, when executed, comprise:Docket No. 0222-15WOPT receiving blood analyte data corresponding to the plurality of blood analytes; integrating timestamps to the blood analyte data; determining one or more trends associated with the blood analyte data; comparing the one or more trends to predetermined thresholds; and determining a risk prediction of one or more medical complications based on whether the one or more trends meet a condition relative to the predetermined thresholds; and displaying at least one of the blood analyte data and the risk prediction in a display unit, wherein the display unit is communicatively coupled to the computing unit.

10. The method of claim 9, further comprising regulating, via a control unit, the flow of the blood through the sensor unit.

11. The method of claim 9, further comprising calibrating the sensor unit before the computing unit can execute the program instructions.

12. The method of claim 9, wherein the plurality of blood analytes comprises blood gases, electrolytes, metabolites, cellular evaluations and temperature.

13. The method of claim 9, wherein the program instructions further comprise notifying a user of patient abnormalities using visual, auditory or haptic displays.

14. The method of claim 9, wherein the computing unit is integrated with electronic medical records.

15. The method of claim 14, wherein the predetermined thresholds are established by analyzing preexisting population data and historical data associated with the patient from the electronic medical records using a trained machine learning model.

16. The method of claim 9, wherein the condition is based on one or more deviations from the predetermined thresholds.

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