Assemblies and associated methods for recirculating body fluids, including therapeutic filtration or conditioning - Patents.com

Abstract

Fluid management systems and associated methods for the withdrawal and subsequent reinfusion of bodily fluids, such as cerebrospinal fluid, may be used for therapeutic and / or diagnostic purposes. Disclosed are fluid management systems and associated methods that include the withdrawal of a bodily fluid followed by reinfusion of the same fluid after conditioning, e.g., thermal conditioning, filtration, introduction or removal of chemical or biological agents, or other therapeutic process(es). The disclosed fluid management systems may further include in-line measurement and / or detection of analytes, contaminants, and / or analysis of physical properties of the fluid to diagnose or detect disease, infection, or toxicity.

Description

[Technical field]

[0001] FIELD OF THE DISCLOSURE The present disclosure relates generally to fluid management systems and related methods. [Background technology]

[0002] 2. Description of Related Art Extracorporeal therapy in the current technology involves the withdrawal and reinfusion of blood. This is done therapeutically at the bedside, such as in hemodialysis and peritoneal dialysis renal replacement therapy. Blood is also withdrawn and processed in apheresis techniques using laboratory equipment to remove targeted elements, and then reintroduced. A third example of extracorporeal therapy is that of ECMO, extracorporeal membrane oxygenation. In this approach, blood is pumped through a device that bypasses the heart and lungs externally, removing carbon dioxide and adding oxygen before returning the blood to the body. However, the body volumes of other body fluids, such as cerebrospinal fluid (CSF), are insufficient for the approaches described in the current technology.

[0003] Various medical conditions involving central nervous system trauma or disease affecting the brain, spinal cord, and adjacent tissues are very difficult to diagnose or treat with existing methods and equipment. For diagnosis, existing lab-based tests require removal of a CSF sample for in vitro evaluation. This is limited by the reduced volume of CSF a patient can tolerate in one sitting. Given this, existing technologies are unable to deliver timely solutions, such as in the case of leptomeningeal cancer, where low concentrations of analytes or biomarkers are present in the CSF. Similarly, there are many rare brain diseases for which existing tests are not cost-effective due to their low prevalence in the population.

[0004] With regard to therapy, existing technologies rely on intravenous delivery, providing few options for delivery of therapeutic agents that do not cross the blood-brain barrier. Recently, there have been attempts to deliver such therapeutic agents directly into the CSF, thereby bypassing the blood-brain barrier, but limitations of existing therapeutic and fluid management systems make this process cumbersome, minimally effective, or dangerous. There are a variety of reasons for this.

[0005] The flow mechanisms, patterns, and pathways of CSF from generation to circulation and subsequent resorption are poorly understood. It is unclear from the medical literature where in the patient's anatomy therapeutic agents should be delivered to maximize the benefit of treating a particular tumor type or location. The Kelli-Monroe doctrine is a widely accepted explanation of intracranial pressures, but does not adequately explain the range of patients found in modern ICUs. The glymphatic system has only been identified within the last decade.

[0006] The introduction of therapeutic agents also increases the total volume of fluid within the skull, which typically results in patients with cerebral dysregulation developing elevated intracranial pressure (ICP) unless the total fluid volume and / or pressure is carefully managed by external drainage. Existing technology does not include provisions for pressure management during the introduction of exogenous fluid. Existing systems for external drainage of CSF do not support simultaneous monitoring, drainage, and infusion and are notoriously difficult to manage. They are known to be staffing challenges and a source of medical errors in clinical settings that determine patient morbidity and mortality. Summary of the Invention [Means for solving the problem]

[0007] Disclosed are fluid management systems and related methods that include the withdrawal of a bodily fluid followed by reinfusion of the same fluid after conditioning, e.g., thermal conditioning, filtration, introduction or removal of a chemical or biological agent, or other therapeutic process(es). The disclosed fluid management systems may further include in-line measurement and / or detection of analytes, contaminants, and / or analysis of physical properties of the fluid to diagnose or detect disease, infection, or toxicity.

[0008] A fluid management system configured for recirculation and drainage of bodily fluid may be summarized as comprising a patient interface assembly including a first fluid line, a second fluid line, a fluid collection reservoir, and at least one wearable sensor subassembly, where 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, and a control system assembly including at least one fluid detection subassembly, at least one logic device, and a plurality of flow control mechanisms, where the logic device implements an algorithm to control 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, and where the plurality of flow control mechanisms are configured to variably withdraw the bodily fluid from the first patient access location, reinfuse the bodily fluid at the second patient access location, and drain the bodily fluid to the fluid collection reservoir.

[0009] The patient interface assembly may include a third fluid line having one end configured for connection to an exogenous fluid source including an exogenous fluid. The patient interface assembly may include a mixing chamber configured to mix the exogenous fluid with the bodily fluid prior to reinfusion at the second patient access location. The wearable sensor subassembly may include at least one pressure sensor in direct fluid communication with the bodily fluid, and the control system assembly may be configured to monitor changes in pressure of the bodily fluid. The wearable sensor subassembly may include at least one analyte sensor in direct fluid communication with the bodily fluid, and the control system assembly may be configured to monitor changes in concentration of a target analyte of the bodily fluid. The wearable sensor subassembly may include at least one physiological sensor, and the control system assembly may be configured to monitor changes in a physiological parameter. The method of withdrawing the bodily fluid may be gravity-based drainage. The bodily fluid may be cerebrospinal fluid.

[0010] The first and second patient access locations may be proximate to a single anatomical marker, and the at least one wearable sensor subassembly may be configured to be attached to the patient proximate to the single anatomical marker. The anatomical marker may be an ear canal. The first patient access location may be proximate to a first anatomical marker, and the second patient access location may be proximate to a second anatomical marker. The at least one wearable sensor subassembly may include a first wearable sensor subassembly and a second wearable sensor subassembly, and the first wearable sensor subassembly may be configured to be attached to the patient proximate to the first anatomical marker, and the second wearable sensor subassembly may be configured to be attached to the patient proximate to the second anatomical marker. The first anatomical marker may be an ear canal, and the second anatomical marker may be a lumbar region of the spine.

[0011] A fluid management system configured for regulation and recirculation of bodily fluid may be summarized as comprising a patient interface assembly including a first fluid line, a second fluid line, at least one wearable sensor subassembly, and at least one fluid regulation assembly, where 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, and a control system assembly including at least one fluid detection subassembly, at least one logic device, and a plurality of flow control mechanisms, where the logic device implements an algorithm to control 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, and where the plurality of flow control mechanisms are configured to variably withdraw the bodily fluid from the first patient access location, reinfuse the bodily fluid at the second patient access location, and expel the bodily fluid to the fluid collection reservoir.

[0012] The bodily fluid regulating assembly may be a thermal regulating assembly configured to regulate the temperature of the bodily fluid in the second fluid line upstream of the second patient access location. The thermal regulating assembly may be configured to increase the temperature of the bodily fluid. The thermal regulating assembly may be configured to decrease the temperature of the bodily fluid. The patient interface assembly may include at least one temperature sensor configured to measure the temperature of the bodily fluid, and the control system assembly may be configured to control operation of the thermal regulating assembly based on an input from the temperature sensor. The control system assembly may be configured to receive a body temperature input and regulate an output of the thermal regulating assembly based on the input. The bodily fluid regulating assembly may be a filtration assembly configured to capture one or more contaminants from the bodily fluid. The bodily fluid may be cerebrospinal fluid.

[0013] A fluid management system configured for recirculation and drainage of bodily fluids may be summarized as a system comprising a patient interface assembly including a bidirectional fluid line, a fluid collection reservoir, and at least one wearable sensor subassembly, the fluid line configured to connect to an implanted catheter at a patient access location, and a control system assembly including at least one fluid detection subassembly, at least one logic device, and a plurality of flow control mechanisms, the logic device implementing an algorithm that controls 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 configured to variably withdraw the bodily fluid from the patient access location, temporarily store the bodily fluid, reinfuse the bodily fluid at the patient access location, and drain the bodily fluid to the fluid collection reservoir. [Brief description of the drawings]

[0014] [Figure 1] 1 shows a fluid drainage and recirculation management system. [Diagram 2] 1 illustrates a cartridge subassembly of the patient interface assembly. [Diagram 3] FIG. 1 illustrates a top view of a wearable sensor subassembly of a patient interface assembly of a fluid drainage and recirculation management system. [Figure 4A] 1 illustrates a first schematic of a wearable sensor subassembly of a patient interface assembly of a fluid drainage and recirculation management system. [Figure 4B] 1 illustrates a second schematic of a wearable sensor subassembly of a patient interface assembly of a fluid drainage and recirculation management system. [Figure 5A] 1 shows a drip chamber with a fluid detection subassembly and filter attached. [Figure 5B] 1 illustrates a fluid detection subassembly that includes a drip chamber with a removable or replaceable filter. [Figure 5C] 1 shows a cartridge subassembly with a removable or replaceable filter. [Figure 6] 1 shows a simplified operational diagram of the drainage control algorithm. [Figure 7] 1 shows a simplified operational diagram of the drainage and recirculation control algorithm. [Figure 8] 13 shows a simplified operational diagram of another drainage and recirculation control algorithm. [Figure 9A] 1 shows a first view of a thermal regulation assembly of a fluid drainage and recirculation management system. [Figure 9B] 1 shows a second view of the thermal regulation assembly of the fluid drainage and recirculation management system. [Figure 10A] 1 illustrates a heat transfer subassembly of a thermal regulating assembly. [Figure 10B] 1 illustrates a heat transfer subassembly of a thermal regulating assembly. [Figure 11] 1 shows a fluid drainage and recirculation management system with thermal regulation. [Figure 12A] FIG. 1 illustrates a top cutaway view of a wearable sensor subassembly of a patient interface assembly of a fluid drainage and recirculation management system. [Figure 12B] FIG. 14 illustrates a side cutaway view of another wearable sensor subassembly of a patient interface assembly of a fluid drainage and recirculation management system. [Figure 13A] 1 shows the fluid lines of a fluid drainage and recirculation management system. [Figure 13B] 1 illustrates another fluid line of the fluid drainage and recirculation management system. [Figure 13C] 1 illustrates another fluid line of the fluid drainage and recirculation management system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] The present disclosure fills an unmet need in the art by describing systems and associated methods that facilitate the delivery of diagnostic or therapeutic agents into a biological body in an automated or semi-automated manner while simultaneously monitoring relevant physiological parameters (such as physical movement, fluid pressure and / or flow rate) and / or managing certain parameters (such as ICP, flow rate) within clinically safe ranges, maintaining and / or driving natural flow patterns of fluid(s) within the body, and / or delivering therapeutic processes (such as hyper / hypothermia, filtration, etc.). The present disclosure provides these benefits in a configuration that requires minimal clinical expertise to operate, facilitating broader clinical adoption and ensuring that patients are treated safely, consistently, and with maximum efficacy. Currently, no devices exist that can safely maintain and / or drive fluid movement through these pathways. For example, in certain cases it may be clinically advantageous to withdraw CSF from one location (e.g., the spine), modify the withdrawn CSF in some way (e.g., heating or cooling the CSF, injecting a chemotherapy agent, filtering out free-floating cancer cells or blood components, adjusting the pH, etc.), and then reinject the CSF into a different location (e.g., the ventricles).

[0016] There is an urgent need for early stratification of disease, as well as improved therapeutic devices and methods for safe and effective delivery of chemotherapy and other therapeutic agents and processes directly into / from the CSF while managing the patient's ICP within safe limits. Additionally, there is a need for devices that can aid in clinical research to advance medical understanding of the absorption of exogenous and various bodily fluids (e.g., CSF, interstitial fluid, etc.). Finally, there is a need for bedside diagnostic devices that reduce overall testing and permanently remove less fluid to facilitate rapid diagnosis. The introduction of more effective and efficient CSF screening methods could significantly improve current technology and reduce the overall time to diagnosis.

[0017] Disclosed are fluid management systems and associated methods for withdrawing and subsequently reinfusing one or more bodily fluid(s) for diagnostic or therapeutic purposes while providing synchronized tracking and / or control of various physiological parameters. Such systems may further advance the scientific understanding of the natural flow mechanisms, flow patterns, and flow paths of various bodily fluids by providing more detailed tracking and management of physiological parameters than is possible with the current state of the art.

[0018] Body fluids in this context may include CSF, blood, interstitial fluid, lymph, and the like.

[0019] Physiological parameters in this context may include patient position, orientation, movement, or gait, fluid pressure (such as ICP), fluid temperature, opacity, particulate count, flow rate, or drainage volume, and any other relevant parameters useful in the therapeutic treatment of various medical conditions, including brain tumors and metastases, leptomeningeal cancer, Parkinson's disease, Alzheimer's disease, and related dementias.

[0020] Patient position is an important variable that this disclosure brings to light, given the physics of pressure created by a closed system of fluids. The pressure in the lateral ventricles when the patient is lying down is not the same as when the patient is sitting up. A typical anatomical lying patient has a generally uniform 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 spine region is dramatically higher, caused by the column of fluid in the spine. The pressure in the lateral ventricles may be slightly lower than when lying down, depending on the position of the head. In many studies, this position is often temporary while the patient is lying down (parallel to the floor) for certain calculations such as opening lumbar pressure or cerebral perfusion pressure. This disclosure allows characterization of position and motion relative to drainage, while the recirculation characteristics allow various clinical evaluations to be performed on the same patient population. This disclosure also aids in the evaluation of chronic patients during activities of daily living related to the behavior and settings of the implanted shunt.

[0021] The disclosed fluid management systems may include one or more treatment assemblies to achieve a desired therapeutic goal(s).

[0022] The disclosed fluid management systems may include one or more diagnostic assemblies for detecting and / or measuring specific analytes, contaminants, or toxins in a target fluid, such as the presence and / or concentration of bacteria, viruses, proteins, chemicals, e.g., exogenous compounds, elements, hormones, or other biomarkers.

[0023] Therapeutic or diagnostic assemblies and associated processes may include regulation of heat for hypothermic or hyperthermic therapy, detection, capture, and / or removal of harmful compounds or foreign contaminants such as bacteria (or bacterial by-products), viruses, cellular (e.g., cancerous cells), proteins (e.g., tau protein, or proteins associated with the presence of cancerous cells or congenital diseases), amyloid beta peptides, prions, chemical compounds or molecules, chemical elements (e.g., heavy metals), hormones, biomarkers, glucose, lactate, pyruvate, gamma aminobutyric acid (GABA), glutamate, neurotransmitters, other bodily fluids (e.g., blood contaminating CSF), exogenous compounds (e.g., pharmaceuticals), introduction of therapeutic agents such as chemotherapy drugs, saline, non-metabolized sugar solutions, etc.

[0024] In certain embodiments, the disclosed system may include a patient interface assembly and a control system assembly. Embodiments of the disclosed system may include a disposable patient interface assembly and a durable control system assembly. In other embodiments, the disclosed system may be fully durable or fully disposable.

[0025] In certain embodiments, the control system assembly may include one or more pump mechanisms for positive displacement of one or more fluids, one or more of which may be bodily fluid(s) and / or exogenous fluid(s).

[0026] In certain embodiments, the patient interface assembly may include fluid lines for connecting a patient at two or more access locations to withdraw one or more bodily fluid(s) from one or more location(s) and reinfuse the bodily fluid(s) and / or exogenous fluid(s) at one or more location(s).

[0027] In other embodiments, the disclosed systems may be configured to recirculate one or more bodily fluid(s) back into the body. In certain embodiments, the disclosed systems may be configured to inject one or more exogenous fluid(s) into the body. In certain embodiments, the disclosed systems may be configured to mix one or more withdrawn bodily fluid(s) with one or more exogenous fluid(s) or compound(s) and inject the mixture into the body.

[0028] In certain embodiments, the disclosed system may be configured to transport CSF from one anatomical location to another for diagnostic purposes, such as detecting a CSF leak. A CSF leak is a condition in which fluid leaks through a tear or hole in the dura. Although imaging is currently used to diagnose CSF leaks, many suspected idiopathic leaks are difficult to identify or localize. Therefore, the present disclosure provides an alternative method of detection by intentionally increasing or decreasing the pressure and / or volume of CSF at various locations along the brain-spinal column, particularly on either side of the suspected area, and recording changes in physical parameters (e.g., pressure over time, pressure response to changes in body position, etc.) or patient symptoms (e.g., headache, balance, gait, etc.).

[0029] 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 diagnostic benefit of the fluid loss itself, or as a means of analyzing more fluid outside the body than would otherwise be possible to remove for analysis.

[0030] In certain embodiments, the disclosed systems can be configured to provide therapeutic drainage of one or more bodily fluid(s).

[0031] In certain embodiments, the disclosed systems can be configured to make specific therapeutic decisions related to user-defined set points and measured physiological parameters. For example, the disclosed systems can be configured to recirculate CSF, infuse exogenous fluids while monitoring ICP, and intermittently drain CSF from the recirculation loop as needed to maintain ICP according to a user-defined range or set point.

[0032] In certain embodiments, the disclosed systems may include any combination of the following subassemblies in operative communication: pump mechanism(s), heating and / or cooling element(s), filtration element(s), flow control actuator(s), user interface(s), flow shutoff actuator(s), etc.

[0033] In certain embodiments, the disclosed systems may include in operative communication various sensing modalities such as pressure sensor(s), orientation sensor(s), acceleration sensor(s), motion sensor(s), flow sensor(s), bubble sensor(s), liquid level sensor(s), optical sensor(s), temperature sensor(s), electrochemical sensor(s), analyte sensors, and the like.

[0034] In various embodiments, the sensors may be located within the patient interface assembly, while in other embodiments the sensors may be located within the control system assembly or may be provided as a separate assembly which may be durable or disposable depending on the particular sensor type and construction.

[0035] FIG. 1 is a diagram showing a simplified schematic of a representative embodiment of the disclosed system in relation to a patient's anatomy, the system being configured for CSF recirculation and drainage, infusion of therapeutic fluids, and monitoring and control of various physiological parameters.

[0036] 1, the disclosed system may include a control system assembly 200 and a patient interface assembly 100. The patient interface assembly 100 may include a cartridge subassembly 101 for interfacing with the control system assembly, a fluid recirculation loop including a fluid withdrawal tube 103 and a reinfusion tube 406, which may also be referred to as bidirectional tubes, for withdrawing fluid at one anatomical location and reinfusing fluid at the same or a different anatomical location, a fluid collection reservoir 102 for permanently removing fluid from the recirculation loop, wearable sensor subassemblies 104a and 104b configured for attachment to a patient proximate an appropriate anatomical marker such as the external auditory canal (EAM) or the L4 / L5 spinal process, electrical cables 116a and 116b for electrical communication and DC power distribution between the cartridge subassembly and the wearable sensor subassembly, and fluid-tight connectors 106a and 106b for connecting to implanted catheters 107a and 107b (e.g., ventricular catheters, parenchymal catheters, lumbar catheters, etc.).

[0037] In certain embodiments, the disclosed system may further include an exogenous fluid reservoir 401 and an exogenous fluid tube 404 for injecting exogenous fluid, as well as a mixing chamber 407 for mixing the exogenous fluid with fluid in the bodily fluid recirculation loop.

[0038] In other embodiments, the electrical cables 116a and 116b may be replaced with battery power and / or one or more wireless communication protocol(s) (e.g., Wi-Fi, BLE, IR, etc.).

[0039] In certain embodiments, the disclosed system may include multiple patient interface assemblies 100.

[0040] As shown in FIG. 1, the recirculation flow of CSF may be directed externally from an anatomical location in the head (e.g., the ventricles, the subarachnoid space, etc.) to an anatomical location in the spine (e.g., L4 / L5, C1 / C2, etc.). In a related embodiment, the recirculation flow of CSF may be reversed by swapping the connections between the fluid withdrawal and reinfusion tubes and the implanted catheters, so that the fluid-tight connector 106a is connected to the implanted catheter 107b, and the fluid-tight connector 106b is connected to the implanted catheter 107a. In other embodiments, the fluid connections and implanted catheters may be in locations other than those shown herein. For example, fluid may be withdrawn from the ventricles and reinfused into the brain parenchyma, or fluid may be removed from the thoracic region of the spine and reinfused into the lumbar region of the spine. In certain embodiments, the disclosed system may 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 therapeutic or diagnostic benefit.

[0041] FIG. 2 is a diagram showing a detailed view of an exemplary embodiment of cartridge subassembly 101.

[0042] As shown in FIG. 2, cartridge subassembly 101 may include a cartridge housing 130 with gripping features 131 for inserting and removing the cartridge subassembly from the control system assembly.

[0043] The cartridge subassembly 101 may further comprise a first flexible tube 141a that may be variably tightened or released by a first flow control mechanism of the control system assembly to disable or enable gravity-based drainage of the target bodily fluid to the drip chamber 143, T-joint 411, and a second flexible tube 141b that may be variably tightened or released by a second flow control mechanism of the control system assembly to enable gravity-based drainage of the fluid from the drip chamber to the drainage collection reservoir 102 when released for permanent removal from the recirculation loop.

[0044] The drip chamber may include a drip orifice 163 that produces a drip of a known size and may interface with a drip detector of the control system assembly. The flow rate may be calculated by the system by counting the number of drips detected by a corresponding drip detector of the control system assembly and multiplying the drip number by the known drip size.

[0045] The cartridge subassembly 101 may further include a flow shutoff feature having an associated button 142 that may be temporarily decoupled by pressing the button to allow bodily fluids to drain.

[0046] The cartridge subassembly 101 may further comprise a fluid-tight fitting 144 for optional connection, removal, and / or replacement of the drainage reservoir 102.

[0047] The cartridge subassembly 101 may further include an array of electrical contacts 145 that interfaces with a corresponding array in the control system assembly for electrical communication and DC power distribution between the control system assembly and the cartridge subassembly.

[0048] In certain embodiments, the cartridge subassembly 101 may include a first peristaltic pump head 410a for controlling flow from an exogenous fluid reservoir to a mixing chamber described elsewhere herein, and a second peristaltic pump head 410b for controlling flow rate from the drip chamber back to the body. The first and second peristaltic pump heads may interface with a pump motor of a control system assembly. In other embodiments, certain aspects of the peristaltic pump assembly shown as being located within the cartridge subassembly may instead be located within the console assembly, or vice versa. In still other embodiments, the pumping action described may be achieved via completely different means (piezoelectric pumps, diaphragm pumps, etc.).

[0049] FIG. 3 is a diagram illustrating an exemplary embodiment of wearable sensor subassembly 104 (previously shown in FIG. 1 as 104a and 104b).

[0050] As shown in FIG. 3, the wearable sensor subassembly 104 may include a flow path 110 with a fluid inlet 111a and a fluid outlet 111b opposite the fluid inlet, pressure sensors 119a and 119b for measuring the pressure of the fluid, and a direction sensor 115 (e.g., accelerometer, gyroscope, etc.) for detecting patient movement. The wearable sensor subassembly 104 may further include a housing 117 with 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 substrates such as FR4, Kapton, polyester, etc.) and may utilize a single communication and power interface along an electrical cable 116. In other embodiments, the sensor may be located at any other suitable location along the fluid line (e.g., within the cartridge, between the cartridge and the drainage reservoir, etc.). In still other embodiments, certain sensors that do not directly contact the fluid in the drainage or recirculation fluid line(s) may be located within the control system assembly or may be provided as separate assemblies that can be used in operative communication with the control system assembly.

[0051] In other embodiments, the electrical cables may be replaced with battery power and / or one or more wireless communication protocol(s) (e.g., Wi-Fi, BLE, etc.).

[0052] 4A and 4B are schematic representations of a wearable sensor subassembly 104 according to certain embodiments of the present disclosure, in which a direction sensor (A) and multiple pressure sensors (P1 and P2) are mounted on a rigid or semi-rigid member (B) at fixed intervals (d). FIG. 4A illustrates the wearable sensor subassembly 104 in a horizontal orientation with respect to the gravity vector (g). FIG. 4B illustrates the wearable sensor subassembly 104 in a vertical orientation with respect to the gravity vector (g).

[0053] In a particular aspect of this embodiment, the directional sensor(s) detect the orientation of the wearable sensor subassembly 104, thereby facilitating the calculation of the expected pressure difference ΔP according to the following equation:

[0054] ΔP 予想 =ρ(Δh)

[0055] where ρ is the density of the fluid (e.g., density of CSF, saline, blood, urine, exogenous fluids, etc.) and Δh is the height difference between pressure sensors P2 and P1 relative to the gravity vector.

[0056] As shown in FIG. 4A, when the wearable sensor subassembly 104 is oriented horizontally with respect to the gravity vector (g), the height difference (Δh) between the two pressure sensors (P1 and P2) is zero (i.e., Δh=0, and therefore ΔP 予想 =0), the pressure measurements from the multiple pressure sensors (P1 and P2) are substantially equal.

[0057] As shown in FIG. 4B, when the wearable sensor subassembly 104 is oriented perpendicular 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 予想 =ρd).

[0058] If the orientation of any of the wearable sensor subassemblies is other than horizontal or vertical, the height difference between the pressure sensors (P1 and P2) varies between 0 and d based on the vertical component of their orientation with respect to the gravity vector (g). The corresponding expected pressure difference is ΔP 予想 =0 to ΔP 予想 =ρd range.

[0059] In certain embodiments of the control system algorithm, one or both pressure sensors can be used to determine the actual measured fluid pressure, while ΔP 予想 (explained above) and ΔP 実際Any substantial deviation between the pressure sensor readings (obtained directly from the pressure sensor readings) can be used by the system to detect faults in the pressure sensor (electrical faults, drift in sensor accuracy, biofouling, etc.).

[0060] It will be apparent to one of ordinary skill in the art that the present disclosure is applicable to measuring gauge or absolute pressure, either of which can be accomplished by the type of sensors used for P1 and P2, or by including a separate atmospheric pressure sensor(s) outside the fluid path (such as in the control system assembly) for the calculation of gauge pressure.

[0061] The disclosed approach provides two layers of redundancy. First, because each pressure sensor in the wearable sensor subassembly 104 is positioned near an anatomical marker for the fluid of interest, the second pressure sensor provides a direct "backup" that allows the system to continue to operate even if it is determined that any one sensor is no longer functioning properly. Second, the system can detect even the slightest drift in the accuracy of the wearable sensor subassembly and take appropriate action (such as notifying the user) before such errors become clinically significant.

[0062] The disclosed approach differs from existing two-sensor systems in which one sensor measures pressure in a target fluid line and a second sensor measures pressure in a separate reference line, with both pressure sensors located at locations other than their associated anatomical markers (e.g., a pole-mounted console or a waist-worn wearable). In such systems, the true pressure of the target fluid (e.g., true ICP) is calculated as the difference between the pressure in the drain line and the pressure in the separate reference line.

[0063] The two sensor placements described in the prior art provide no redundancy and limited opportunity for error checking, leaving patients susceptible to sensor drift and similar disturbances. Co-locating two pressure and directional sensors in substantial proximity to relevant anatomical markers, as described in this disclosure, enables unprecedented levels of measurement accuracy and clinical safety.

[0064] It will be appreciated that the wearable sensor subassembly 104 must be small enough and lightweight to facilitate attachment to specific anatomical markers (such as the EAM located on the head, or L4-L5 located in the lumbar region of the lower back) to achieve practical use. Thus, the use of small enough pressure sensors suitable for prolonged contact with bodily fluids and also with sufficient accuracy and precision to enable clinical utility is important in achieving the disclosed embodiments. Additionally, the spacing between sensors must be small enough to facilitate a suitable overall footprint of the assembly, which places further constraints on the accuracy of the pressure sensors to enable useful drift detection, as described elsewhere herein. For example, spacing on the order of a few centimeters is only useful if the pressure sensors can resolve pressure differences on the order of a few millimeters of water (mmH2O). Until recently, such pressure sensors were unknown in the industry, making such embodiments impractical. However, recent technological developments now allow for spacings (d) in the range of 1-2 cm using small (2-3 mm wide) pressure sensors with an accuracy of around ±1 mmH2O, resulting in an overall footprint of 2-5 cm2 with the characteristics described herein. 2 A range of practical implementations of wearable sensor subassemblies are now possible.

[0065] 5A and 5B are diagrams illustrating a cross-sectional view of an exemplary embodiment of a drip and level detection interface between the cartridge subassembly and the control system assembly.

[0066] 5A and 5B, the cartridge subassembly may include a drip chamber 143 with a drip orifice 163 that produces a known size fluid drip 412. 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 drift sensor(s) 414 for detecting the fluid drip 412 and one or more fluid level sensors 415a and 415b for detecting an accumulated fluid level 416 in the drip chamber. The fluid detection subassembly 413 may also be referred to as a drip and fluid level sensor, a bodily fluid flow measurement sensor, etc.

[0067] In other embodiments, drip detection and fluid level detection may be accomplished by two (or more) separate sensors rather than the combined sensor shown in Figures 5A and 5B. In certain embodiments, the drip and fluid level sensor(s) may be optical (such as infrared), ultrasonic, or any other suitable sensing technology.

[0068] In other embodiments, the drip and fluid level sensor assembly may further comprise an optical sensor(s) that monitors color, opacity, or other parameter(s) that may indicate a corresponding change in the viscosity or density of the fluid, which is the actual amount of fluid contained in each drip. In such cases, the disclosed system may include an algorithm that compensates for such changes in drip volume to maintain an accurate measurement of the flow rate.

[0069] In other embodiments, as shown in Figure 5A, the cartridge subassembly may further comprise a filter 417 for removing biological or non-biological materials from the drawn 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 means suitable for selective filtration of the target material to be removed. The filter 417 may be removable and replaceable, as shown in Figure 5B.

[0070] 5C is a diagram showing a detailed view of an exemplary embodiment of the cartridge subassembly 101 including a filter 417. As shown in FIG. 5C, the cartridge subassembly 101 may further include a filter 417, which may be removable and replaceable via fluid tight fittings 418a and 418b. The filter 417 may be located between the outflow of the drip chamber 143 and the inflow of the T-fitting 411. In an alternative embodiment, the filter 417 may be located at a point along the reinfusion tube 406.

[0071] Figures 6, 7 and 8 are block diagrams illustrating simplified representative algorithms that may be used by the disclosed system. The system may include multiple modes of operation depending on the type of therapy delivered and / or sensing modality used, and thus the algorithm(s) may differ from those shown in Figures 6 or 7 or 8 in various ways without departing from the spirit of the present disclosure.

[0072] As shown in FIG. 6, the disclosed system may be configured to provide controlled therapeutic drainage of bodily fluids according to user-defined flow rate or pressure set points while monitoring user-defined alarm threshold values ​​for parameters such as pressure and flow rate. In certain embodiments, the system may be further configured to monitor the output of one or more sensors to detect one or more analytes or contaminants associated with disease, toxicity, and / or infection, and issue alarm(s) or notification(s) to the user when such analytes, contaminants, or toxins are detected. In certain embodiments, the system may be further configured to utilize algorithm(s) derived from human analysis and analytics, machine learning, neural network(s), artificial intelligence, or similar methods to deliver more nuanced personalized management of specific medical conditions, specific physiological parameters, and the like.

[0073] In certain embodiments, as shown in FIG. 8, the disclosed system may be configured to utilize detection or concentration of analytes, contaminants, or toxins to provide controlled therapeutic recirculation of bodily fluids according to an algorithm(s) or user-defined targets. For example, in the case of subdural or subarachnoid hemorrhage, the disclosed system may measure the blood concentration of the CSF continuously or at defined intervals and drain the CSF whenever the concentration exceeds an acceptable low level. Detection of blood concentration may be measured by an analyte sensor or by a physiological sensor that optically evaluates the color of the CSF or uses light sensing at various wavelengths to identify the composition of the bodily fluids.

[0074] The disclosed system may further be configured to automatically manage the fluid level in the drip chamber utilizing an algorithm such as that shown in Figure 7. The system variably operates one or more mechanism(s), such as peristaltic pump(s), pinch valves, etc., to control the flow of drained bodily fluids and / or exogenous fluids either back to the patient from whom it was drawn in the form of autotransfusion, or to a drainage collection reservoir for permanent removal of the bodily fluids from the recirculation loop, according to various user-defined parameters, such as target pressure and / or flow rate, pressure and / or flow rate tolerances, and / or pressure and / or flow rate alarm thresholds.

[0075] The control system assembly 200 may include one or more processors (microcontrollers, microprocessors, FPGAs, SOMs, etc.) and one or more storage devices (EEPROM, flash memory, etc.) that store instructions that, when executed by the one or more processors, cause the control system assembly 200 to perform the algorithms described herein.

[0076] 9A is a diagram illustrating an exemplary embodiment of a thermal regulating assembly that may be included in the disclosed system. As shown in FIG. 9A, thermal regulating assembly 700 may include patient fluid line 701 with patient fluid inlet 702a and patient fluid outlet 702b opposite the fluid inlet, thermal regulating cartridge subassembly 706, and thermal regulating jacket 703 with working fluid inlet port 704a and working fluid outlet port 704b, and heat transfer subassembly 711 with working fluid inlet tube 705a and working fluid outlet tube 705b containing working fluid 730.

[0077] In certain embodiments, the thermal conditioning cartridge subassembly may include a heating or cooling element (e.g., cartridge heater, thermoelectric cooler, etc.) for heating or cooling the working fluid, and a pump or similar means for circulating the working fluid around the working fluid. 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 related embodiments, the cartridge subassembly may interface with a durable assembly (such as a console assembly) that may provide power, thermal conditioning, pumping, etc., either directly or indirectly to the working fluid.

[0078] The thermal regulation assembly may further include a temperature measurement subassembly 720 that includes a temperature sensor, 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 subassemblies described elsewhere herein may include the temperature measurement subassembly.

[0079] The actuating fluid inlet and outlet ports may be made of rigid (plastic, metal, ceramic, etc.) or flexible (silicone, TPE, etc.) materials depending on the configuration of the disclosed system and the anatomical location where it will be used clinically. In certain applications (e.g., cranial therapy, neonatology, etc.), the patient fluid tubing, actuating fluid tubing, fittings, etc. may be small and flexible enough to be constrained to the patient's anatomy without applying excessive force (e.g., weight of the tubing) to the patient's anatomy.

[0080] The patient and working fluid tubes may be made from compliant or semi-compliant materials (silicone, TPE, polyurethane, pebax, etc.) depending on the configuration of the disclosed system and the anatomical location where it will be clinically used. The tubes may be constrained to the patient's anatomy by sutures, wearable devices, or any other suitable means.

[0081] The working fluid can be any fluid suitable for heat transfer (eg, water, liquid silicone, mineral oil, etc.).

[0082] 9B is a diagram illustrating another exemplary embodiment of a thermal regulation assembly 700. As shown in FIG. 9B, the thermal regulation assembly 700 may further comprise a thermal monitoring inflow sensor 720a and / or a thermal monitoring outflow sensor 720b to provide an electrical signal corresponding to a temperature of the patient fluid, which may be interpreted by a patient fluid temperature control subassembly of the control system assembly. The thermal control subassembly may comprise one or more logic device(s) (e.g., microcontroller, microprocessor, etc.) capable of implementing one or more control algorithm(s) to regulate the temperature and / or flow rate of the working fluid, thereby regulating the rate of heat transfer between the working fluid and the patient fluid based on the electrical signal from the thermal monitoring inflow sensor 720a and / or the thermal monitoring outflow sensor 720b. Electrical signals from the thermal monitoring inflow sensor 720a and / or thermal monitoring outflow sensor 720b may be transmitted to the thermal regulating cartridge subassembly 706 or the control system assembly 200 via electrical cable 116c, or the electrical signals may be transmitted wirelessly (e.g., via Wi-Fi, BLE, IR, etc.) and used by the control system assembly 200 as inputs to control the flow rate of the patient fluid.

[0083] 10A and 10B are diagrams illustrating alternative embodiments of the heat transfer subassembly 711. FIG. 10A shows a partial cutaway view of a section of a patient fluid line 701 encapsulated by a thermal regulating jacket 703. As shown in FIG. 10A, 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 wire(s), straight wire, wire ring, or wire mesh. In still other embodiments, the wire braid 740 may be replaced with or used in conjunction with thermally conductive fillers or fibers (e.g., carbon, metal spheres or flakes, etc.) included directly into the material of the patient fluid line 701.

[0084] 10B, a portion of patient fluid line 701 may include a wire braid 740 embedded in or on its wall, which may be electrically connected to electrical interfaces 750a and 750b, which may in turn be connected to electrical wires 751a and 751b, such that wire braid 740 may be directly heated by passing an electrical current between wires 751a and 751b. In alternative embodiments, wire braid 740 may be configured as one or more helically wound wire(s), straight wires, or a wire mesh.

[0085] 11, the disclosed system may include a control system assembly 200 and a patient interface assembly 100. Patient interface assembly 100 may further include a thermal regulation assembly 700, as described elsewhere herein.

[0086] The disclosed system may further include one or more sensors, some of which may be in fluid communication, as shown in Figures 12A and 12B, and Figures 13A, 13B, and 13C. As shown in Figures 12A and 12B, these sensors may be co-located on a PCB 113 (including substrates such as FR4, Kapton, polyester, etc.) of the wearable sensor subassembly 104, and may include one or more optical sensors 114, directional sensors 115, pressure sensors 119a and 119b, and / or fluid communication sensors 132.

[0087] In related embodiments, wireless technology may be used to achieve power transmission (such as inductive or resonant inductive coupling) and / or signal communication (such as RF, infrared, etc.). In other related embodiments, the wearable sensor subassembly 104 may be internally powered (battery, capacitor, etc.). In further embodiments, multiple wearable sensor subassemblies may be positioned at any suitable location along the fluid withdrawal or drainage line 103 or reinfusion tube 406.

[0088] As shown in Figures 13A, 13B, and 13C, a fluid communication sensor(s) optimized for detecting one or more of the analytes or contaminants described elsewhere herein may be placed directly on and / or in any suitable location in a fluid line 127, such as a bodily fluid withdrawal or drainage line 103 or a reinfusion tube 406. Figure 13A illustrates the use of a sensing band 128, such as a colorimetric coated sensor, that delivers a visually detectable result directly to a user. Figure 13B illustrates the use of a continuous sensing strip 129, which may include a colorimetric coating as described herein, or may include a flex circuit adhered to the inner surface of the fluid line 127 or suspended within the bodily fluid of the fluid line 127.

[0089] In other embodiments, the fabric of the fluid line 127 itself may include a sensing material, such as a leuco dye, which may function as a colorimetric sensor due to its chemical form change properties triggered by heat, light, or changes in pH. In a related embodiment, as shown in Figure 13C, the electronic fluid communication sensor 130 may be embedded in the fluid line itself using overmolding, co-extrusion, or other manufacturing methods and an electrical cable 131 or flat flex circuit that may be fabricated inside the tubing and / or attached to the inside or outside of the fluid line 127.

[0090] In other embodiments, the sensor and / or illumination source may be located in any other suitable location along the fluid line (e.g., in a second sensor assembly, in the cartridge, between the cartridge and the drainage reservoir, etc.). In still other embodiments, the sensor and / or its illumination source(s) that do not directly contact the fluid in the drainage line may be located within the control system assembly or may be provided as a separate assembly that can be used in operative communication with the control system assembly 200. In related embodiments, the sensor(s) and / or illumination source(s) may be partially or completely housed in an opaque or semi-opaque housing(s) to minimize and / or control interference from ambient light.

[0091] U.S. Provisional Patent Application Nos. 63 / 315,910, filed March 2, 2022, and 63 / 315,930, filed March 2, 2022, from which this application claims priority, are incorporated herein by reference in their entireties. Aspects of the various embodiments described above can be combined to provide further embodiments. In general, the terms used in the following claims should not be construed as limiting the claims to the specific embodiments disclosed in the specification and claims, but rather as including all possible embodiments along with the full scope of equivalents to which such claims are entitled.

Claims

1. 1. A body fluid management system configured for recirculation and drainage of body fluids, the body fluid management system comprising: a patient interface assembly including a first fluid line, a second fluid line, a bodily fluid collection reservoir, and at least one wearable sensor subassembly, the first fluid line configured to connect to a first implanted catheter at a first patient access location and the second fluid line configured to connect to a second implanted catheter at a second patient access location; and a control system assembly including at least one fluid detection subassembly, at least one logic device, and a plurality of flow control mechanisms; the logic device implements an algorithm that controls 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 system, wherein the plurality of flow control mechanisms are configured to variably withdraw the bodily fluid from the first patient access location, reinfuse the bodily fluid at the second patient access location, and drain the bodily fluid into the bodily fluid collection reservoir.

2. The system of claim 1 , wherein the patient interface assembly includes a third fluid line, one end of which is configured for connection to an exogenous fluid source containing an exogenous fluid.

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

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

5. 10. 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 the control system assembly is configured to monitor changes in a concentration of a target analyte in the bodily fluid.

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

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

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

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

10. The system of claim 9 , wherein the anatomical marker is the ear canal.

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

12. 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, the first wearable sensor subassembly configured to be attached to a patient near the first anatomical marker and the second wearable sensor subassembly configured to be attached to the patient near the second anatomical marker.

13. 12. The system of claim 11, wherein the first anatomical marker is the ear canal and the second anatomical marker is the lumbar region of the spine.

14. 1. A body fluid management system configured for regulation and recirculation of body fluids, the body fluid management system comprising: a patient interface assembly including a first fluid line, a second fluid line, at least one wearable sensor subassembly, and at least one fluid regulating assembly, the first fluid line configured to connect to a first implanted catheter at a first patient access location and the second fluid line configured to connect to a second implanted catheter at a second patient access location; and a control system assembly including at least one fluid detection subassembly, at least one logic device, and a plurality of flow control mechanisms; the logic device implements an algorithm that controls 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 system, wherein the plurality of flow control mechanisms are configured to variably withdraw the bodily fluid from the first patient access location, reinfuse the bodily fluid at the second patient access location, and drain the bodily fluid into the bodily fluid collection reservoir.

15. 15. The system of claim 14, wherein the bodily fluid regulating assembly is a thermal regulating assembly, the thermal regulating assembly configured to regulate a 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 assembly is configured to increase the temperature of the bodily fluid.

17. The system of claim 15 , wherein the thermal regulation assembly is configured to decrease the temperature of the bodily fluid.

18. 16. The system of claim 15, wherein the patient interface assembly includes at least one temperature sensor configured to measure the temperature of the bodily fluid, and 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 assembly is configured to receive a body temperature input and adjust an output of the thermal regulation assembly based on the input.

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

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

22. 1. A body fluid management system configured for recirculation and drainage of body fluids, the body fluid management system comprising: a patient interface assembly including a bidirectional fluid line, a fluid collection reservoir, and at least one wearable sensor subassembly, the fluid line configured to connect to an implanted catheter at a patient access location; and a control system assembly including at least one fluid detection subassembly, at least one logic device, and a plurality of flow control mechanisms; the logic device implements an algorithm that controls 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 system, wherein the plurality of flow control mechanisms are configured to variably withdraw the bodily fluid from the patient access location, temporarily store the bodily fluid, reinfuse the bodily fluid at the patient access location, and drain the bodily fluid into the bodily fluid collection reservoir.

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