Assembly for bodily fluid recirculation including therapeutic filtration or modulation and related methods

Abstract

Body fluid management systems and related methods for extraction and subsequent reinfusion of body fluids, such as cerebrospinal fluid, may be used for therapeutic and / or diagnostic purposes.

Description

Background Art Technical Field

[0001] The present disclosure relates generally to bodily fluid management systems and related methods.

[0002] Description of the Prior Art

[0003] Extracorporeal treatments in the prior art involve drawing and returning blood. This is done at the bedside, in treatments such as hemodialysis and peritoneal dialysis renal replacement therapies. Blood is also drawn, processed using laboratory equipment using apheresis techniques to remove target components, and then reinfused. A third type of extracorporeal treatment is ECMO, or extracorporeal membrane oxygenation. With this method, blood bypasses the heart and lungs from the outside, is pumped through a device that removes carbon dioxide and adds oxygen, and then the blood is returned to the body. However, the volume of other body fluids, such as cerebrospinal fluid (CSF), is not sufficient for the methods described in the prior art.

[0004] Various medical conditions involving trauma or central nervous system diseases affecting the brain, spinal cord and adjacent tissues are difficult to diagnose or treat using existing methods and equipment. In order to make a diagnosis, existing laboratory-based tests require the removal of CSF samples for in vitro evaluation. This is limited by the amount of CSF reduction that a patient can tolerate in a single treatment. In view of this, the existing technology cannot provide a timely solution, such as in the case of leptomeningeal cancer, where low concentrations of analytes or biomarkers are present in the CSF. Similarly, many rare brain diseases are not cost-effective due to their low incidence in the population.

[0005] In terms of treatment, existing technologies rely on intravenous delivery and offer few options for delivering therapeutic agents that do not cross the blood-brain barrier. Recent attempts to deliver such therapeutic agents directly into the CSF, thereby bypassing the blood-brain barrier, have made this procedure cumbersome, ineffective, or dangerous due to limitations in existing treatments and fluid management systems. There are multiple reasons for this.

[0006] The mechanisms, patterns, and pathways of CSF flow from production, circulation, to reabsorption are poorly understood. It is unclear from the medical literature where in the patient's anatomy a therapeutic agent should be delivered to maximize therapeutic benefit for a specific tumor type or location. The Kelly-Monroe theory is a widely accepted explanation for intracranial pressure, but in modern times it is insufficient to fully explain the various types of patients seen in the ICU. Only in the last decade has the brain's glymphatic system been identified.

[0007] The introduction of therapeutic agents also increases the total amount of fluid within the skull, which often increases intracranial pressure (ICP) in patients with cerebral autoregulatory disorders if the total fluid volume and / or pressure are not carefully managed via external drainage. The prior art does not include pressure management measures during the introduction of exogenous fluids. Existing CSF external drainage systems do not support simultaneous monitoring, drainage, and infusion, and are very difficult to manage. They are well known to be the source of staffing difficulties and medical errors leading to patient morbidity and mortality in clinical practice. Summary of the invention

[0008] Bodily fluid management systems and related methods are disclosed that include extracting bodily fluid and then returning the same bodily fluid after conditioning (such as thermal conditioning, filtration, introduction or removal of chemical or biological agents, or other therapeutic processes). The disclosed bodily fluid management systems may also include online measurement and / or detection of analytes, contaminants, and / or analysis of physical properties of the fluid for diagnosis or detection of disease, infection, or toxicity.

[0009] A body fluid management system configured for recycling and drainage of body fluids can be summarized as including: a patient interface component, the patient interface component including a first fluid line, a second fluid line, a body fluid collection reservoir and at least one wearable sensor sub-component, wherein the first fluid line is configured to be connected to a first implanted catheter at a first patient access location, and the second fluid line is configured to be connected to a second implanted catheter at a second patient access location; and a control system component, the control system component including at least one fluid detection sub-component, at least one logic device and a plurality of flow control mechanisms; wherein the logic device implements an algorithm based on input from at least one of the fluid detection sub-component and the wearable sensor sub-component to control the operation of the plurality of flow control mechanisms; wherein the plurality of flow control mechanisms are configured to variably extract the body fluid from the first patient access location, reinfuse the body fluid at the second patient access location, and drain the body fluid into the body fluid collection reservoir.

[0010] The patient interface assembly may include a third fluid line, one end of which is configured to be connected to an exogenous fluid source containing an exogenous fluid. The patient interface assembly may include a mixing chamber, which is configured to mix the exogenous fluid and the body fluid before reinfusion at the second patient access position. The wearable sensor subassembly may include at least one pressure sensor in direct fluid communication with the body fluid, and the control system assembly may be configured to monitor changes in pressure of the body fluid. The wearable sensor subassembly may include at least one analyte sensor in direct fluid communication with the body fluid, and the control system assembly may be configured to monitor changes in target analyte concentration in the body fluid. The wearable sensor subassembly may include at least one physiological sensor, and the control system assembly may be configured to monitor changes in physiological parameters. The method of extracting the body fluid may be gravity-based drainage. The body fluid may be cerebrospinal fluid.

[0011] The first patient access location and the second patient access location may be proximate to a single anatomical landmark, and the at least one wearable sensor subassembly may be configured to be attached to the patient proximate to the single anatomical landmark. The anatomical landmark may be an external auditory canal. The first patient access location may be proximate to a first anatomical landmark, and the second patient access location may be proximate to a second anatomical landmark. The at least one wearable sensor subassembly may include a first wearable sensor subassembly and a second wearable sensor subassembly, the first wearable sensor subassembly may be configured to be attached to the patient proximate to the first anatomical landmark, and the second wearable sensor subassembly may be configured to be attached to the patient proximate to the second anatomical landmark. The first anatomical landmark may be an external auditory canal, and the second anatomical landmark may be a lumbar region of a spine.

[0012] A body fluid management system configured for regulation and recirculation of body fluids can be summarized as including: a patient interface component, the patient interface component including a first fluid line, a second fluid line, at least one wearable sensor sub-component and at least one body fluid regulation component, wherein the first fluid line is configured to be connected to a first implanted catheter at a first patient access location, and the second fluid line is configured to be connected to a second implanted catheter at a second patient access location; and a control system component, the control system component including at least one fluid detection sub-component, at least one logic device and a plurality of flow control mechanisms; wherein the logic device implements an algorithm based on input from at least one of the fluid detection sub-component and the wearable sensor sub-component to control the operation of the plurality of flow control mechanisms; wherein the plurality of flow control mechanisms are configured to variably extract the body fluid from the first patient access location, reinfuse the body fluid at the second patient access location, and drain the body fluid into the body fluid collection reservoir.

[0013] The body fluid regulation component may be a thermal regulation component, and the thermal regulation component may be configured to adjust the temperature of the body fluid in the second fluid line upstream of the second patient access location. The thermal regulation component may be configured to increase the temperature of the body fluid. The thermal regulation component may be configured to reduce the temperature of the body fluid. The patient interface component may include at least one temperature sensor, the at least one temperature sensor configured to measure the temperature of the body fluid, and the control system component may be configured to control the operation of the thermal regulation component based on input from the temperature sensor. The control system component may be configured to receive a body temperature input and adjust the output of the thermal regulation component based on the input. The body fluid regulation component may be a filter component configured to capture one or more contaminants from the body fluid. The body fluid may be cerebrospinal fluid.

[0014] A body fluid management system configured for recycling and drainage of body fluids can be summarized as including: a patient interface component, the patient interface component including a bidirectional body fluid line, a body fluid collection reservoir and at least one wearable sensor sub-component, wherein the body fluid line is configured to be connected to an implanted catheter at a patient access location; and a control system component, the control system component including at least one fluid detection sub-component, at least one logic device and a plurality of flow control mechanisms; wherein the logic device implements an algorithm based on input from at least one of the fluid detection sub-component and the wearable sensor sub-component to control the operation of the plurality of flow control mechanisms; wherein the plurality of flow control mechanisms are configured to variably extract the body fluid from the patient access location, temporarily store the body fluid, reinfuse the body fluid at the patient access location, and drain the body fluid into the body fluid collection reservoir. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 A body fluid drainage and recirculation management system is shown.

[0016] Figure 2 A cassette subassembly of a patient interface assembly is shown.

[0017] Figure 3 A top view of a wearable sensor subassembly of a patient interface assembly of a bodily fluid drainage and recirculation management system is shown.

[0018] Figure 4A A first schematic diagram of a wearable sensor subassembly of a patient interface assembly of a bodily fluid drainage and recirculation management system is shown.

[0019] Figure 4B A second schematic diagram of a wearable sensor subassembly of a patient interface assembly of a bodily fluid drainage and recirculation management system is shown.

[0020] Figure 5A Shown is a fluid detection subassembly and a drip chamber with an attached filter.

[0021] Figure 5B A fluid sensing subassembly and a drip chamber with a removable or replaceable filter are shown.

[0022] Figure 5C A cassette subassembly with a removable or replaceable filter is shown.

[0023] Figure 6 A simplified operational diagram of the drainage control algorithm is shown.

[0024] Figure 7 A simplified operational diagram of the drainage and recirculation control algorithm is shown.

[0025] Figure 8 A simplified operational diagram of another drainage and recirculation control algorithm is shown.

[0026] Fig. 9A A first view of a thermal regulation assembly of a bodily fluid drainage and recirculation management system is shown.

[0027] Fig. 9B A second view of a thermal regulation assembly of a bodily fluid drainage and recirculation management system is shown.

[0028] Fig. 10A A heat transfer subassembly of a thermal regulation assembly is shown.

[0029] Fig. 10B A heat transfer subassembly of a thermal regulation assembly is shown.

[0030] Fig.11 A body fluid drainage and recirculation management system with thermal regulation function is shown.

[0031] Fig. 12A A top cross-sectional view of a wearable sensor subassembly of a patient interface assembly of a bodily fluid drainage and recirculation management system is shown.

[0032] Fig. 12B A side cross-sectional view of another wearable sensor subassembly of a patient interface assembly of a bodily fluid drainage and recirculation management system is shown.

[0033] Fig.13A The fluid lines of the body fluid drainage and recirculation management system are shown.

[0034] Fig. 13B Another fluid line of the body fluid drainage and recirculation management system is shown.

[0035] Fig. 13C Another fluid line of the body fluid drainage and recirculation management system is shown. DETAILED DESCRIPTION

[0036] The present disclosure satisfies the unmet needs in the art by describing the following systems and related methods: facilitating diagnosis or delivering therapeutic agents to an organism, and simultaneously monitoring relevant physiological parameters (physical movement, fluid pressure and / or flow, etc.) and / or managing certain parameters (ICP, flow rate, etc.) within a clinically safe range, maintaining and / or driving the natural flow pattern of fluids in the body, and / or delivering treatment processes (high / low temperature regulation, filtration, etc.) in an automatic or semi-automatic manner. The present disclosure provides these benefits in a configuration that requires minimal clinical expertise to operate, thereby promoting a wider range of clinical applications and ensuring that patients receive safe, consistent and maximally effective treatment. There is currently no device that can safely maintain and / or drive fluid flow through these pathways. For example, in some cases, it may be clinically beneficial to extract CSF from one location (e.g., the spine), change the extracted CSF in some way (e.g., heat or cool the CSF, inject chemotherapy drugs, filter out free cancer cells or blood components, adjust pH, etc.), and then return the CSF to a different location (e.g., the ventricle).

[0037] There is an urgent need for improved treatment devices and methods to stratify the disease earlier and to safely and effectively deliver chemotherapy and other therapeutic agents and procedures directly to / from the CSF while keeping the patient's ICP within safe limits. In addition, there is a need for devices that can support clinical research to promote medical understanding of the absorption of exogenous and various body fluids (such as CSF, interstitial fluid, etc.). Finally, there is a need for a bedside diagnostic device that requires fewer overall tests and less fluid to be permanently removed to facilitate rapid diagnosis. Existing technologies can be significantly improved by introducing more effective and efficient CSF screening methods, thereby reducing overall diagnostic time.

[0038] Disclosed are bodily fluid management systems and related methods that extract and subsequently return one or more bodily fluids for diagnostic or therapeutic purposes while providing simultaneous tracking and / or control of various physiological parameters. Such systems may also further the scientific understanding of the natural flow mechanisms, flow patterns, and flow pathways of various bodily fluids by providing more detailed tracking and management of physiological parameters than is currently available.

[0039] In this context, body fluids may include CSF, blood, interstitial fluid, lymph, etc.

[0040] In this context, physiological parameters may include patient position, orientation, movement or gait, fluid pressure (such as ICP), fluid temperature, opacity, particle count, flow rate or drainage volume; and any other relevant parameters that may be used to treat various medical conditions (including brain tumors and metastases, leptomeningeal cancer, Parkinson's disease, Alzheimer's disease and related dementias, etc.).

[0041] Patient position is a key variable elucidated by the present disclosure, given the physics of pressure generated by fluid in a closed system. The pressure in the lateral ventricles when the patient is lying down is not the same as the pressure in the lateral ventricles when the patient is sitting up. A patient lying flat with typical anatomy has roughly consistent pressure throughout the central nervous system (from the lumbar region of the spine to the skull). When the same patient stands upright, the pressure in the lumbar region rises dramatically, which is caused by the column of fluid in the spine. Depending on the position of the head, the pressure in the lateral ventricles may be slightly lower than when lying flat. Although many studies lay patients flat (parallel to the floor) for specific calculations, such as open lumbar pressure or cerebral perfusion pressure, this posture is usually temporary. The present disclosure allows characterization of position and movement relative to the drainage, while the recirculation characteristics enable various clinical assessments to be performed on the same patient population. The present disclosure also supports assessments of chronic patients in daily life activities related to the behavior and setting of implanted shunts.

[0042] The disclosed bodily fluid management systems may include one or more therapeutic components for achieving desired therapeutic objectives.

[0043] The disclosed bodily fluid management system may include one or more diagnostic components for detecting and / or measuring the presence and / or concentration of certain analytes, contaminants or toxins in a target bodily fluid, such as bacteria, viruses, proteins, chemicals (including exogenous compounds), elements, hormones or other biomarkers.

[0044] Therapeutic or diagnostic components and associated processes may include thermal regulation for hypothermic or hyperthermic treatment, detection, capture and / or removal of harmful compounds or foreign contaminants, such as bacteria (or bacterial byproducts), viruses, cells (such as cancer cells), proteins (such as tau protein or proteins associated with the presence of cancer cells or congenital diseases), amyloid beta peptides, prions, compounds or molecules, chemical elements (such as heavy metals), hormones, biomarkers, glucose, lactate, pyruvate, gamma-aminobutyric acid (GABA), glutamate, neurotransmitters, other body fluids (such as CSF contaminated with blood), exogenous compounds (such as drugs); introduction of therapeutic agents, such as chemotherapeutic drugs, saline, non-metabolized sugar solutions, etc.

[0045] In certain embodiments, the disclosed systems may include a patient interface assembly and a control system assembly. Embodiments of the disclosed systems include a disposable patient interface assembly and a durable control system assembly. In other embodiments, the disclosed systems may be fully durable or fully disposable.

[0046] In certain embodiments, the control system components may include one or more pump mechanisms for positive displacement of one or more fluids, where the one or more fluids may be bodily fluids and / or exogenous fluids.

[0047] In certain embodiments, a patient interface assembly may include fluid lines for connecting to a patient at two or more access locations for withdrawing one or more bodily fluids from one or more locations and returning bodily fluids and / or exogenous fluids at one or more locations.

[0048] In other embodiments, the disclosed systems can be configured to recirculate body fluids back into the body. In certain embodiments, the disclosed systems can be configured to infuse one or more exogenous fluids into the body. In certain embodiments, the disclosed systems can be configured to mix one or more extracted body fluids with one or more exogenous fluids or compounds and infuse the mixture into the body.

[0049] In certain embodiments, the disclosed system may be configured to transfer CSF from one anatomical location to another anatomical location for diagnostic purposes, such as for detecting CSF leaks. CSF leaks refer to situations in which fluid escapes through tears or holes in the dura mater. Although imaging is currently used to diagnose CSF leaks, many suspected idiopathic leaks are difficult to identify or locate. Therefore, the present disclosure provides an alternative detection method by intentionally increasing or decreasing CSF pressure and / or volume at different locations along the cerebrospinal column, particularly on either side of the suspected area, and recording changes in physical parameters (e.g., changes in pressure over time, pressure response to position changes, etc.) or patient symptoms (e.g., headaches, balance, gait, etc.).

[0050] In certain embodiments, the disclosed systems can be configured to remove CSF from an anatomical location, temporarily store it outside the body, and then return it to the same anatomical location for the diagnostic benefit of fluid reduction itself, or as a means of analyzing more fluid in vitro than might otherwise be removed for analysis.

[0051] In certain embodiments, the disclosed systems can be configured to provide therapeutic drainage of one or more bodily fluids.

[0052] In certain embodiments, the disclosed systems can be configured to make certain treatment decisions related to user-defined set points and measured physiological parameters. For example, the disclosed systems can be configured to recirculate CSF and infuse exogenous fluids while monitoring ICP, and intermittently drain CSF from the recirculation circuit as needed to maintain ICP according to a user-defined range or set point.

[0053] In certain embodiments, the disclosed systems may include any combination of the following subcomponents in operable communication: pump mechanisms, heating and / or cooling elements, filter elements, flow rate control actuators, user interfaces, flow shutoff actuators, and the like.

[0054] In certain embodiments, the disclosed system may include various sensing modalities that can communicate operatively, such as: pressure sensors, orientation sensors, acceleration sensors, motion sensors, flow sensors, bubble sensors, liquid level sensors, optical sensors, temperature sensors, electrochemical sensors, analyte sensors, etc.

[0055] In various embodiments, the sensor can be located within the patient interface assembly. In other embodiments, the sensor can be located within the control system assembly, or provided as a separate assembly that can be durable or disposable, depending on the type and configuration of the specific sensor.

[0056] Figure 1is a line drawing showing a simplified diagram of a representative embodiment of the disclosed system as it relates to a patient anatomy, wherein the system is configured for recirculation and drainage of CSF, infusion of therapeutic fluids, and monitoring and control of various physiological parameters.

[0057] like Figure 1 As depicted, the disclosed system may include a control system assembly 200 and a patient interface assembly 100 . The patient interface assembly 100 may include a box subassembly 101 for interfacing with a control system assembly; a body fluid recirculation circuit, the body fluid recirculation circuit including a body fluid extraction tube 103 and a return tube 406, which may also be referred to as a bidirectional tube, for extracting body fluid at one anatomical location and reinfusing body fluid at the same anatomical location or a different anatomical location; a body fluid collection reservoir 102, the body fluid collection reservoir being used to permanently remove body fluid from the recirculation circuit; wearable sensor subassemblies 104a and 104b, the wearable sensor subassemblies being configured to be attached to the patient near appropriate anatomical landmarks (such as the external auditory canal (EAM) or the L4 / L5 spinous processes); cables 116a and 116b, the cables being used for electrical communication and DC power distribution between the box subassembly subassembly and the wearable sensor subassembly; and liquid-tight connectors 106a and 106b, the liquid-tight connectors being used to connect implanted catheters 107a and 107b (such as ventricular catheters, parenchymal catheters, lumbar catheters, etc.).

[0058] In certain embodiments, the disclosed system may further include an exogenous fluid reservoir 401 and an exogenous fluid tube 404 for infusing an exogenous fluid and a mixing chamber 407 for mixing the exogenous fluid with the fluid in the body fluid recirculation circuit.

[0059] In other embodiments, the cables 116a and 116b may be replaced with battery power and / or one or more wireless communication protocols (eg, Wi-Fi, BLE, IR, etc.).

[0060] In certain embodiments, the disclosed system may include more than one patient interface assembly 100 .

[0061] like Figure 1As depicted, the recirculation flow of CSF can be directed externally to the anatomical position (e.g., L4 / L5, C1 / C2, etc.) of the spine from the anatomical position (e.g., ventricle, subarachnoid space, etc.) in the head. In a related embodiment, the recirculation flow of CSF can be reversed by exchanging the connection between the body fluid extraction and return tube and the implanted catheter so that the liquid-tight connector 106a is connected to the implanted catheter 107b and the liquid-tight connector 106b is connected to the implanted catheter 107a. In other embodiments, the catheter of the fluid connection and implantation can be located at a position other than that shown herein. For example, fluid can be extracted from the ventricle and returned to the brain parenchyma, or fluid can be removed from the thoracic region of the spine and returned to the lumbar region of the spine. In certain embodiments, the disclosed system can be configured to remove CSF from the anatomical position, temporarily store it in vitro, and then return it to the same anatomical position to obtain treatment or diagnostic benefits.

[0062] Figure 2 is a line drawing showing a detailed view of a representative embodiment of the cassette subassembly 101 .

[0063] like Figure 2 As depicted, the cartridge subassembly 101 may include a cartridge housing 130 having gripping features 131 for inserting and removing the cartridge subassembly from the control system assembly.

[0064] The cassette subassembly 101 may also include a first flexible tube 141a, a three-way connector 411, and a second flexible tube 141b, wherein the first flexible tube can be variably clamped or released by a first flow control mechanism in the control system assembly to prohibit or allow the target body fluid to be drained into the drip chamber 143 based on gravity, and the second flexible tube can be variably clamped or released by a second flow control mechanism in the control system assembly to allow the fluid to be drained from the drip chamber to the drainage collection reservoir 102 based on gravity when released to be permanently removed from the recirculation circuit.

[0065] The drip chamber may include a drip orifice 163, wherein the drip orifice 163 produces a known size of drop and may interface with a drop detector in a control system component. The system may calculate the flow rate by counting the number of drops detected by the corresponding drop detector in the control system component and then multiplying the number of drops by the known drop size.

[0066] The cassette subassembly 101 may also include a flow shutoff feature with an attached button 142, wherein pressing the button may temporarily disengage the flow shutoff feature to allow drainage of bodily fluids.

[0067] The cassette subassembly 101 may also include a fluid-tight fitting 144 for selectively connecting, removing, and / or replacing the drainage reservoir 102 .

[0068] The cassette subassembly 101 may also include an array of electrical contacts 145 to interface with a corresponding array in a control system assembly for electrical communication and DC power distribution between the control system assembly and the cassette subassembly.

[0069] In certain embodiments, the cassette subassembly 101 can include a first peristaltic pump head 410a for controlling the flow rate flowing into the mixing chamber described elsewhere herein from an exogenous fluid reservoir, and a second peristaltic pump head 410b for controlling the flow rate flowing back into the body from the drip chamber. The first peristaltic pump head and the second peristaltic pump head can interface with the pump motor in the control system assembly. In other embodiments, the peristaltic pump assembly is depicted as being positioned in certain aspects of the cassette subassembly and can be positioned in the console assembly instead, and vice versa. In other embodiments, the described pumping action can be realized by completely different means (piezoelectric pump, diaphragm pump, etc.).

[0070] Figure 3 The wearable sensor subassembly 104 (previously in Figure 1 104a and 104b).

[0071] like Figure 3 As depicted, the wearable sensor subassembly 104 may include a flow channel 110 having a fluid inlet 111a and a fluid outlet 111b opposite the fluid inlet, pressure sensors 119a and 119b for measuring fluid pressure, and an orientation sensor 115 (e.g., accelerometer, gyroscope, etc.) for detecting patient movement. The wearable sensor subassembly 104 may also include a housing 117 having suture points 118 for attaching the wearable sensor subassembly 104 to the patient near suitable anatomical markers as described elsewhere herein. The number and location of the suture points may vary depending on the anatomical markers. The sensor and associated components may be co-located on a PCB 113 (including a substrate of FR4, Kapton, polyester, etc.), and a single communication and power interface may be used along the cable 116. In other embodiments, the sensor may be located at any other suitable location along the fluid line (e.g., within a box, between a box and a drainage reservoir, etc.). In other embodiments, certain sensors that do not directly contact the fluid in the drain or recirculation fluid lines may be located within the control system component or provided as separate components that may be in operable communication with the control system component.

[0072] In other embodiments, the cable may be replaced with a battery power source and / or one or more wireless communication protocols (eg, Wi-Fi, BLE, etc.).

[0073] Figure 4A and Figure 4Bis a schematic diagram of a wearable sensor subassembly 104 according to certain embodiments of the present disclosure, wherein an orientation sensor (A) and a plurality of pressure sensors (P1 and P2) are mounted on a rigid or semi-rigid member (B) at a fixed spacing (d). Figure 4A The wearable sensor subassembly 104 is depicted in a horizontal orientation relative to a gravity vector (g). Figure 4B The wearable sensor subassembly 104 is depicted in a vertical orientation relative to the gravity vector (g).

[0074] In certain aspects of this embodiment, the orientation sensor detects the orientation of the wearable sensor subassembly 104, thereby facilitating the calculation of the expected pressure difference ΔP according to the following formula:

[0075] ΔP 预期 =ρ(Δh)

[0076] Where p is the fluid density (eg, density of CSF, saline, blood, urine, exogenous fluid, etc.), and Δh is the height difference between pressure sensors P2 and P1 relative to the gravity vector.

[0077] like Figure 4A As depicted, when the wearable sensor subassembly 104 is oriented horizontally relative to the gravity vector (g), the pressure readings of the plurality of pressure sensors (P1 and P2) are substantially equal because the height difference (Δh) between the two pressure sensors (P1 and P2) is zero (i.e., Δh=0, and therefore ΔP 预期 =0).

[0078] like Figure 4B As depicted, when the wearable sensor subassembly 104 is oriented vertically relative to the gravity vector (g), the pressure difference between the multiple pressure sensors (P1 and P2) is maximized because the height difference (Δh) between the two pressure sensors is also maximized (i.e., Δh=d, so ΔP 预期 =ρd).

[0079] In any wearable sensor subassembly orientation other than horizontal or vertical, the height difference between the multiple pressure sensors (P1 and P2) will vary between 0 and d based on the vertical component of the orientation relative to the gravity vector (g). The corresponding expected pressure difference will be ΔP 预期 =0 to ΔP 预期 =ρd range.

[0080] In certain embodiments of the control system algorithm, one or two pressure sensors may be used to determine the actual measured fluid pressure, and ΔP 预期 (as described above) and ΔP 实际Any significant deviation between the pressure sensor readings (obtained directly via the pressure sensor readings) can be used by the system to detect pressure sensor failure (electrical failure, sensor accuracy drift, bio-contamination, etc.).

[0081] It will be apparent to one skilled in the art that the present disclosure is applicable to measuring either gauge pressure or absolute pressure, as measurement of either gauge pressure or absolute pressure may be accomplished depending on the type of sensors used for P1 and P2, or by including a separate atmospheric pressure sensor outside the fluid path (such as in a control system component) for calculating gauge pressure.

[0082] The disclosed method provides two layers of redundancy. First, because each pressure sensor in the wearable sensor subassembly 104 is located close to anatomical landmarks of the fluid of interest, the second pressure sensor provides a direct "backup" that can allow the system to continue operating in the event that it is determined that either sensor is no longer functioning properly. Second, the system can detect very small amounts of drift in the accuracy of the wearable sensor subassembly and take appropriate action (such as notifying the user) before these errors become clinically significant.

[0083] The disclosed method differs from existing dual sensor systems in which one sensor measures the pressure in a target fluid line and a second sensor measures the pressure in a separate reference line, and in which both pressure sensors are located at locations other than relevant anatomical landmarks (e.g., in a pole-mounted console or hip-worn wearable device). In such a system, the true pressure of the target fluid (e.g., true ICP) is calculated based on the difference between the pressure in the drainage line and the pressure in the separate reference line.

[0084] The dual sensor arrangements described in the prior art provide no redundancy and have limited opportunities for error checking, leaving patients vulnerable to sensor drift and similar failures. As described in the present disclosure, co-location of two pressure sensors and an orientation sensor substantially close to relevant anatomical landmarks provides unprecedented measurement accuracy and clinical safety.

[0085] It will be appreciated that the wearable sensor subassembly 104 must be small and lightweight enough to be attached to certain anatomical landmarks (such as the EAM located on the head, or L4-L5 located in the lumbar region of the lower back) in order to be of practical use. Therefore, it is critical to implement the disclosed embodiments to use sufficiently small pressure sensors that are suitable for prolonged contact with body fluids and also have sufficient accuracy and precision to achieve clinical practicality. In addition, the spacing between the sensors must be small enough to facilitate a suitable total footprint of the assembly, which imposes further constraints on the accuracy of the pressure sensor to achieve useful drift detection as described elsewhere herein. For example, a spacing distance of the order of a few centimeters is only useful if the pressure sensor can resolve pressure differences on the order of a few millimeters of water column (mmH2O). Such pressure sensors were not known in the art until recently, and therefore such embodiments were not practical. However, due to recent technological developments, using miniature (2-3 mm wide) pressure sensors with an accuracy on the order of ±1 mmH2O, spacings (d) in the range of 1-2 cm are now possible, thereby achieving a total footprint of 2-5 cm with the characteristics described herein. 2 Practical implementation of wearable sensor subassemblies within the scope.

[0086] Figure 5A and Figure 5B is a line drawing showing a cross-sectional view of a representative embodiment of a drip and level sensing interface between a cartridge subassembly and a control system assembly.

[0087] like Figure 5A and Figure 5B As depicted, the cartridge subassembly may include a drip chamber 143 with a drip orifice 163 that produces a fluid drop 412 of known size. The control system assembly may include a fluid detection subassembly 413 that interfaces with the drip chamber. The fluid detection subassembly 413 may include one or more drip sensors 414 for detecting fluid drops 412 and one or more level sensors 415a and 415b for detecting a fluid level 416 accumulated in the drip chamber. The fluid detection subassembly 413 may also be referred to as a drip and level sensor, a bodily fluid flow measurement sensor, or the like.

[0088] In other embodiments, drip detection and level detection may be performed by two (or more) separate sensors instead of one. Figure 5A and Figure 5B In some embodiments, the drip and level sensors can be optical (infrared, etc.), ultrasonic, or any other suitable sensing technology.

[0089] In other embodiments, the drip and level sensor assembly may also include an optical sensor to monitor color, opacity, or other parameters that may indicate corresponding changes in the viscosity or density of the fluid, which may affect the actual amount of fluid contained in each drop. In this case, the disclosed system may include an algorithm to compensate for the changes in drip volume to maintain an accurate measurement of flow rate.

[0090] In other embodiments, Figure 5A As depicted, the cartridge subassembly may also include a filter 417 for removing biological or non-biological material from the extracted fluid. The filter may be mechanical (e.g., a porous membrane such as paper, ePTFE, sintered metal or other media or a mechanical separator, such as a centrifuge), electrochemical, electrostatic, or any other device suitable for selectively filtering the target material to be removed. The filter 417 may be removable and replaceable, such as Figure 5B Depicted.

[0091] Figure 5C 417 is a line drawing showing a detailed view of a representative embodiment of the cassette subassembly 101 including the filter 417. Figure 5C As shown, the cassette subassembly 101 may also include a filter 417 that can be removed and replaced via liquid-tight fittings 418a and 418b. The filter 417 may be located between the outflow end of the drip chamber 143 and the inflow end of the tee connector 411. In alternative embodiments, the filter 417 may be located anywhere along the return line 406.

[0092] Figure 6 , Figure 7 and Figure 8 is a block diagram depicting a simplified representative algorithm that may be employed by the disclosed system. Depending on the type of treatment being performed and / or the sensing modality being employed, the system may include a variety of operating modes, and thus the algorithm may differ in various ways without departing from the spirit of the present disclosure. Figure 6 or Figure 7 or Figure 8 The algorithm shown in .

[0093] like Figure 6Depicted, the disclosed system can be configured to provide controlled therapeutic drainage of body fluids according to a user-defined flow rate or pressure set point, while monitoring the alarm thresholds defined by the user for parameters (such as pressure and flow rate). In certain embodiments, the system can also be configured to monitor the output of one or more sensors for detecting one or more analytes or pollutants associated with disease, toxicity and / or infection, and to send an alarm or notification to the user when such analytes, pollutants or toxins are detected. In certain embodiments, the system can also be configured to utilize algorithms derived from manual analysis and analysis, machine learning, neural networks, artificial intelligence or similar methods to carry out more nuanced and personalized management of certain medical conditions, specific physiological parameters, etc.

[0094] In certain embodiments, such as Figure 8 As depicted, the system can be configured to provide controlled therapeutic recirculation of body fluids using detection or concentration of analytes, contaminants, or toxins according to an algorithm or user-defined goal. For example, in the case of a subdural hemorrhage or subarachnoid hemorrhage, the disclosed system can measure the blood concentration in the CSF continuously or at defined intervals and drain the CSF whenever the concentration exceeds an acceptably low level. Detection of blood concentration can be measured by optical evaluation of the color of the CSF by an analyte sensor or a physiological sensor or by using photoelectric sensing of various wavelengths to identify fluid components.

[0095] The disclosed system may also be configured to utilize, for example, Figure 7 The algorithm depicted in automatically manages the level of fluid in the drip chamber. The system can variably operate one or more mechanisms (such as peristaltic pumps, pinch valves, etc.) to control the flow of drained body fluids and / or exogenous fluids based on various user-defined parameters (such as target pressures and / or flow rates, allowed ranges of pressures and / or flow rates, and / or alarm thresholds for pressures and / or flow rates), either back to the patient from whom the drained body fluids were drawn in the form of autologous transfusions, or into a drain collection reservoir to permanently remove the body fluids from the recirculation circuit.

[0096] The control system component 200 may include one or more processors (microcontrollers, microprocessors, FPGAs, SOMs, etc.) and one or more storage devices (EEPROMs, flash memories, etc.) storing instructions that, when executed by the one or more processors, cause the control system component 200 to perform the algorithms described herein.

[0097] Fig. 9A is a line drawing showing a representative embodiment of a thermal regulation component that may be included in the disclosed system. Fig. 9AAs depicted, the thermal regulation assembly 700 may include a patient fluid line 701 (having a patient fluid inlet 702a and a patient fluid outlet 702b opposite the fluid inlet), a thermal regulation cassette subassembly 706, and a heat transfer subassembly 711, wherein the heat transfer subassembly includes a thermal regulation sleeve 703 (having a working fluid inlet port 704a and a working fluid outlet port 704b), a working fluid inlet tube 705a containing a working fluid 730, and a working fluid outlet tube 705b.

[0098] In certain embodiments, the thermal regulation cassette subassembly may include a heating or cooling element (e.g., a cassette heater, a thermoelectric cooler, etc.) for heating or cooling a working fluid and a pump or similar device for circulating the working fluid in a working fluid circuit. The working fluid may provide heat exchange between the patient fluid and the working fluid to achieve heating or cooling of the patient fluid. In a related embodiment, the cassette subassembly may interface with a durable assembly (director console assembly), which may directly or indirectly provide power, thermal regulation, pumping, etc. for the working fluid.

[0099] The thermal regulation assembly may also include a temperature measurement subassembly 720, which includes a temperature sensor, a thermocouple, or other suitable temperature measurement device for monitoring the temperature of the fluid in the patient fluid line. In other embodiments, the wearable sensor subassembly described elsewhere herein may include the temperature measurement subassembly.

[0100] Depending on the configuration of the disclosed system and the anatomical location of its clinical use, the working fluid inlet and outlet may be made of rigid (plastic, metal, ceramic, etc.) or flexible (silicone, TPE, etc.) materials. For certain applications (e.g., cranial therapy, neonatal, etc.), the patient fluid conduits, working fluid tubes, fittings, etc. may be small and flexible enough to be constrained to the patient anatomy without applying undue forces (e.g., weight of the tubes) to the patient anatomy.

[0101] Depending on the configuration of the disclosed system and the anatomical location of its clinical use, the patient fluid tubes and working fluid tubes can be made of flexible or semi-flexible materials (silicone, TPE, polyurethane, pebax, etc.). The tubes can be constrained to the patient's anatomy by sutures, wearable devices, or any other suitable means.

[0102] The working fluid can be any fluid suitable for heat transfer (eg, water, liquid silicone, mineral oil, etc.).

[0103] Fig. 9B is a line drawing showing another representative embodiment of thermal regulation assembly 700. Fig. 9BAs depicted, the thermal regulation assembly 700 may also include a thermal monitoring inflow sensor 720a and / or a thermal monitoring outflow sensor 720b to provide an electrical signal corresponding to the temperature of the patient fluid, which may be interpreted by a thermal control subassembly in the control system assembly. The thermal control subassembly may include one or more logic devices (such as a microcontroller, a microprocessor, etc.) that may implement one or more control algorithms to adjust the temperature and / or flow rate of the working fluid based on the electrical signals from the thermal monitoring inflow sensor 720a and / or the thermal monitoring outflow sensor 720b, thereby adjusting the heat transfer rate between the working fluid and the patient fluid. The electrical signals from the thermal monitoring inflow sensor 720a and / or the thermal monitoring outflow sensor 720b may be transmitted to the thermal regulation cassette subassembly 706 or the control system assembly 200 via the cable 116c, or the electrical signals may be transmitted wirelessly (e.g., via Wi-Fi, BLE, IR, etc.) and may be used by the control system assembly 200 as an input for patient fluid flow rate control.

[0104] Fig. 10A and Fig. 10B is a line drawing showing an alternative embodiment of heat transfer subassembly 711. Fig. 10A A partial cross-sectional view of a portion of a patient fluid line 701 enclosed by a thermal sleeve 703 is depicted. Fig. 10A As depicted, a portion of the patient fluid line 701 may include a wire braid 740 embedded in or on its wall to enhance heat transfer between the working fluid 730 and the patient fluid. In alternative embodiments, the wire braid 740 may be configured as one or more helically wound wires, straight wires, wire loops, or wire mesh. In other embodiments, the wire braid 740 may be replaced by, or used in conjunction with, a thermally conductive filler or fiber (e.g., carbon, metal spheres or flakes, etc.) directly contained in the material of the patient fluid line 701.

[0105] like Fig. 10B As depicted, a portion of the patient fluid line 701 may include a wire braid 740 embedded in or on a wall thereof, wherein the wire braid 740 may be electrically connected to electrical interfaces 750a and 750b, which in turn may be connected to electrical wires 751a and 751b, wherein the wire braid 740 may be directly heated by passing an electrical current between electrical wires 751a and 751b. In alternative embodiments, the wire braid 740 may be configured as one or more helically wound wires, straight wires, or a wire mesh.

[0106] like Fig.11As depicted, the disclosed system may include a control system assembly 200 and a patient interface assembly 100. The patient interface assembly 100 may also include a thermal regulation assembly 700 as described elsewhere herein.

[0107] The disclosed system may also include Fig. 12A and Fig. 12B as well as Fig.13A , Fig. 13B and Fig. 13C One or more sensors are depicted. Some sensors may be fluid connected and others may not. Fig. 12A and Fig. 12B As depicted, these sensors may be co-located on a PCB 113 (including a substrate of FR4, Kapton, polyester, etc.) of a wearable sensor subassembly 104, and may include one or more optical sensors 114, orientation sensors 115, pressure sensors 119a and 119b, and / or fluid connectivity sensors 132.

[0108] In related embodiments, wireless technology can be used to achieve power transmission (inductive or resonant inductive coupling, etc.) and / or signal communication (RF, infrared, etc.). In other related embodiments, the wearable sensor subassembly 104 can be powered internally (battery, capacitor, etc.). In other embodiments, more than one wearable sensor subassembly can be located at any suitable location along the body fluid extraction or drainage line 103 or the return line 406.

[0109] like Fig.13A , Fig. 13B and Fig. 13C As depicted, a fluid communication sensor optimized for detecting one or more of the analytes or contaminants described elsewhere herein may be located directly on and / or in a fluid line 127 (such as a bodily fluid extraction or drainage line 103 or a return line 406) at any suitable location. Fig.13A Depicted is the use of a sensing strip 128 that delivers visually detectable results directly to a user, such as a colorimetric coating sensor. Fig. 13B Depicted is the use of a continuous sensing strip 129 which may include a colorimetric coating as described herein, or which may include a flexible circuit adhered to the inner surface of the fluid line 127 or suspended within the bodily fluid of the fluid line 127 .

[0110] In other embodiments, the fluid line 127 fabrication itself may include a sensing material, such as a colorless dye, which can be used as a colorimetric sensor because its chemical form changes due to heat, light, or changes in pH. Fig. 13CAs depicted, the electronic fluid communication sensor 130 may be embedded in the fluid line itself using overmolding, coextrusion or other manufacturing methods, and the cable 131 or flat flex circuit may be fabricated within the tubing and / or attached to the interior or exterior of the fluid line 127 .

[0111] In other embodiments, the sensor and / or illumination source may be located at any other suitable location along the fluid line (e.g., within the second sensor assembly, within the cartridge, between the cartridge and the drain reservoir, etc.). In other embodiments, the sensor and / or illumination source thereof that does not directly contact the fluid in the drain line may be located within the control system assembly, or provided as a separate assembly that may be in operable communication with the control system assembly 200. In a related embodiment, the sensor and / or illumination source may be partially or completely enclosed in an opaque or translucent housing to minimize and / or control interference from ambient light.

[0112] This application claims priority to U.S. Provisional Patent Application No. 63 / 315,910 filed on March 2, 2022 and U.S. Provisional Patent Application No. 63 / 315,930 filed on March 2, 2022, which are hereby incorporated by reference in their entirety. Aspects of the various embodiments described above may be combined to provide additional embodiments. In general, in the following claims, the terms used should not be interpreted as limiting the claims to the specific embodiments disclosed in the specification and claims, but should be interpreted to include all possible embodiments and the full range of equivalents to which these claims are entitled.

Claims

1. A body fluid management system configured for recirculation and drainage of body fluids, the body fluid management system comprising: a patient interface assembly comprising a first fluid line, a second fluid line, a bodily fluid collection reservoir, and at least one wearable sensor subassembly, wherein the first fluid line is configured to connect to a first implanted catheter at a first patient access location and the second fluid line is configured to connect to a second implanted catheter at a second patient access location; as well as a control system assembly, the control system assembly comprising at least one fluid detection subassembly, at least one logic device, and a plurality of flow control mechanisms; wherein the logic device implements an algorithm to control the operation of the plurality of flow control mechanisms based on input from at least one of the fluid detection subassembly and the wearable sensor subassembly; The plurality of flow control mechanisms are configured to variably extract the bodily fluid from the first patient access site, return the bodily fluid at the second patient access site, and drain the bodily fluid into the bodily fluid collection reservoir. 2 . The system of claim 1 , wherein the patient interface assembly comprises a third fluid line, one end of the third fluid line being configured to be connected to an exogenous fluid source comprising an exogenous fluid.

3. The system of claim 2, wherein the patient interface assembly comprises a mixing chamber configured to mix the exogenous fluid and the bodily fluid prior to reinfusion at the second patient access location.

4. The system of claim 1 , wherein the wearable sensor subassembly includes at least one pressure sensor in direct fluid communication with the bodily fluid, and wherein the control system assembly is configured to monitor changes in pressure of the bodily fluid.

5. The system of claim 1 , wherein the wearable sensor subassembly comprises at least one analyte sensor in direct fluid communication with the bodily fluid, and wherein the control system assembly is configured to monitor changes in a target analyte concentration in the bodily fluid.

6. The system of claim 1 , wherein the wearable sensor subassembly includes at least one physiological sensor, and wherein the control system assembly is configured to monitor changes in a physiological parameter.

7. The system of claim 1, wherein the method of extracting the body fluid is gravity-based drainage.

8. The system of claim 1, wherein the body fluid is cerebrospinal fluid.

9. The system of claim 1 , wherein the first patient access location and the second patient access location are proximate to a single anatomical landmark, and wherein the at least one wearable sensor subassembly is configured to be attached to the patient proximate to the single anatomical landmark.

10. The system of claim 9, wherein the anatomical landmark is the external auditory canal.

11. The system of claim 1, wherein the first patient access location is proximate to a first anatomical landmark and the second patient access location is proximate to a second anatomical landmark.

12. The system of claim 11, wherein the at least one wearable sensor subassembly comprises a first wearable sensor subassembly and a second wearable sensor subassembly, wherein the first wearable sensor subassembly is configured to be attached to the patient proximate the first anatomical landmark, and the second wearable sensor subassembly is configured to be attached to the patient proximate the second anatomical landmark.

13. The system of claim 11, wherein the first anatomical landmark is the external auditory canal and the second anatomical landmark is the lumbar region of the spine.

14. A bodily fluid management system configured for regulation and recirculation of bodily fluids, the bodily fluid management system comprising: a patient interface assembly comprising a first fluid line, a second fluid line, at least one wearable sensor subassembly, and at least one bodily fluid regulation assembly, wherein the first fluid line is configured to connect to a first implanted catheter at a first patient access location and the second fluid line is configured to connect to a second implanted catheter at a second patient access location; as well as a control system assembly, the control system assembly comprising at least one fluid detection subassembly, at least one logic device, and a plurality of flow control mechanisms; wherein the logic device implements an algorithm to control the operation of the plurality of flow control mechanisms based on input from at least one of the fluid detection subassembly and the wearable sensor subassembly; The plurality of flow control mechanisms are configured to variably extract the bodily fluid from the first patient access site, return the bodily fluid at the second patient access site, and drain the bodily fluid into the bodily fluid collection reservoir.

15. The system of claim 14, wherein the bodily fluid regulation component is a thermal regulation component, and wherein the thermal regulation component is configured to adjust the temperature of the bodily fluid in the second fluid line upstream of the second patient access location.

16. The system of claim 15, wherein the thermal regulation component is configured to increase the temperature of the body fluid.

17. The system of claim 15, wherein the thermal regulation component is configured to reduce the temperature of the body fluid.

18. The system of claim 15, wherein the patient interface assembly comprises at least one temperature sensor configured to measure the temperature of the bodily fluid, and wherein the control system assembly is configured to control operation of the thermal regulation assembly based on input from the temperature sensor.

19. The system of claim 15, wherein the control system component is configured to receive a body temperature input and adjust an output of the thermal regulation component based on the input.

20. The system of claim 14, wherein the bodily fluid conditioning component is a filtration component configured to capture one or more contaminants from the bodily fluid.

21. The system of claim 14, wherein the body fluid is cerebrospinal fluid.

22. A bodily fluid management system configured for recirculation and drainage of bodily fluids, the bodily fluid management system comprising: a patient interface assembly comprising a bidirectional bodily fluid line, a bodily fluid collection reservoir, and at least one wearable sensor subassembly, wherein the bodily fluid line is configured to connect to an implanted catheter at a patient access site; as well as a control system assembly, the control system assembly comprising at least one fluid detection subassembly, at least one logic device, and a plurality of flow control mechanisms; wherein the logic device implements an algorithm to control the operation of the plurality of flow control mechanisms based on input from at least one of the fluid detection subassembly and the wearable sensor subassembly; The plurality of flow control mechanisms are configured to variably extract the bodily fluid from the patient access site, temporarily store the bodily fluid, return the bodily fluid at the patient access site, and drain the bodily fluid into the bodily fluid collection reservoir.

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