Hemodynamic monitoring system

Abstract

An implantable hemodynamic monitoring system comprising a sensor comprising a substrate and a fiber optic connected to the substrate, the sensor configured to be implanted within a blood vessel, wherein the fiber optic comprises one or more reflective gratings, and an interrogator positioned on a skin surface at a position underlying the implantation site of the sensor enabling wireless communication by passing light through the skin to the sensor. Also described herein is a method of measuring blood pressure.

Description

[0001] HEMODYNAMIC MONITORING SYSTEM

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to U.S. Provisional Patent Application No. 63 / 671,506 filed on July 15, 2024, the contents of which are incorporated by reference herein in its entirety.

[0004] BACKGROUND

[0005] Continuous hemodynamic monitoring is greatly needed for guiding treatment for a broad range of conditions including hypertension (high blood pressure) and heart failure. In both cases, patients routinely use conventional blood pressure (BP) cuffs which only provide a single point of measurement, thus greatly limiting the predictive power of the acquired data. The conventional BP monitor was invented in 1881 and has seen little improvement in the intervening 140 years. The device requires the user to inflate a cuff around the upper arm, a process that is both cumbersome and time consuming. Consequently, widespread adherence to regular BP monitoring is very difficult to achieve. Moreover, the conventional BP cuff only provides a single measurement which is not ideal as it is well known that BP fluctuates throughout the day, thus impairing the ability to discriminate between pathologic BP changes and routine physiologic variation (Muntner, P. et al. Hypertension 73, E35-E66 (2019).). Numerous approaches have been investigated for continuous passive BP measurement including wearables, for example watch-like devices with inflatable straps (Kuwabara, M. et al. J. Clin. Hypertens. 21, 463-469 (2019).; Kuwabara, M. et al. J. Clin. Hypertens. 21, 853- 858 (2019).; Kario, K. et al. J. Clin. Hypertens. 22, 135-141 (2020).), tonometry (Nair, D. et al. J. Hum. Hypertens. 22, 220-222 (2008).; Digiglio, P. et al. Ann. Biomed. Eng. 42, 2278-2288 (2014).), and photoplethysmography (Liu, J. et al. IEEE Trans. Biomed. Eng. 66, 1514-1525 (2019).; Ding, X. R. et al. IEEE Trans. Biomed. Eng. 63, 964-972 (2016).). Thus far, none of these devices have achieved widespread adoption as they have not been proven capable of acquiring clinically actionable data. One of the primary reasons for this is that they are notoriously uncomfortable and require regular calibration.

[0006] Almost half of American adults have high BP which places them at risk for coronary events including strokes and heart attacks. It is well established that tight BP control substantially lowers the incident rates of coronary events (Tsao, C. W. et al. Circulation vol. 145 (2022).). The American Heart Association recommends regular at home BP monitoring; however, adherence is challenging due to a lack of a convenient monitoring modality, and thus only 51% of at-risk adults perform the recommended monitoring (Ostchega, Y. et al. Am. J. Hypertens. 30, 1026-1032 (2017).). The average annual cost of hypertension per patient has been reported to be as high as $14,000, adding up to a total cost of $80 billion per year (Tsao, C. W. et al. Circulation vol. 145 (2022).). Much of this is driven by physician office (34 million), hospital outpatient (3.7 million), and emergency department (914,000) visits (Tsao, C. W. et al. Circulation vol. 145 (2022).) that could be substantially reduced by providing continuous at-home monitoring. This would facilitate optimization of blood pressure lowering strategies including medication titration and personalized data driven dietary and lifestyle guidance.

[0007] Blood pressure monitoring is also of great importance for guiding heart failure (HF) treatment. Approximately 40 million people worldwide have HF and 50% of them will die within 5 years of diagnosis. (Heidenreich, P. A. et al. Circ. Hear. Fail. 6, 606-619 (2013).) In the United States, the total annual cost of HF is estimated to be $70 billion by the end of the decade. (Heidenreich, P. A. et al. Circ. Hear. Fail. 6, 606-619 (2013).) This cost arises as HF is typically characterized by repeated acute decompensation (fluid volume overload) episodes which require urgent medical care. Impaired myocardial pumping leads to lower perfusion of arterial blood and increased heart filling pressures which promote fluid retention. Patients typically report symptoms of breathlessness and fatigue. Treatment involves intravenous administration of diuretics (to reduce fluid volume) and continuous positive airway pressure mask ventilation. These procedures are performed in hospital under continuous supervision for approximately 5 days. Moreover, 1 in 5 patients will be readmitted within 30 days as without continuous clinical observation, it is very challenging to adjust medication (oral diuretics) as needed. (Psotka, M. A. et al. JACC Hear. Fail. 8, 1-11 (2020).) Consequently, HF is the main cause of hospitalization in the United States and Europe with more than 1 million admissions annually in both regions. (Ambrosy, A. P. et al. J. Am. Coll. Cardiol. 63, 1123-1133 (2014).) Given the high cost and poor outcomes, there is considerable interest in developing technology that enables early intervention before progression to acute decompensation. Clinical symptoms such as weight gain, fatigue, and rales are poor predictors of congestion and typically only present after progression to acute decompensation. (Pellicori, P. et al. Eur. J. Heart Fail. 21, 904-916 (2019).) In contrast, hemodynamic changes (elevated filling pressures) provide an early indicator of impending congestion. (Drazner, M. H. et al. Circ. Heart Fail. 1, 170-177 (2008).) Consequently, several implantable sensors have been developed which enable interrogation of hemodynamics either directly through pressure measurement or via analysis of venous cross-sectional area. (Cowie, M. R. et al. HF System Post-Market Study. 48-56 (2022).; Kennel, P. J. et al. JAMA Cardiol. 7, 556-564 (2022).) These implants are positioned in deep vessels, such as the pulmonary artery or inferior vena cava, with measurements acquired via wireless communication with external interrogation unit based on inductive coupling. The implants themselves contain no power source to ensure long term use and a small form factor. Due to the depth of the implants, inductive coupling necessitates a relatively large external interrogation unit to ensure adequate penetration depth and coupling between antennas.

[0008] Thus, there is a need in the art for an implant designed for shallow blood vessels that facilitate wireless communication, enable continuous monitoring and acquisition of a rich dataset with continuous real-time hemodynamic measurements.

[0009] SUMMARY

[0010] In some aspects, the present disclosure relates to an implantable hemodynamic monitoring system comprising a sensor comprising a substrate and a fiber optic connected to the substrate, the sensor configured to be implanted within a blood vessel, wherein the fiber optic comprises one or more reflective gratings, and an interrogator positioned on a skin surface at a position underlying the implantation site of the sensor.

[0011] In some embodiments, the interrogator is integrated into a wearable device. In some embodiments, the interrogator is integrated into a module, wherein the module is configured to be adhered to the skin. In some embodiments, the interrogator is integrated into a handheld device. In some embodiments, the one or more reflective gratings are Fiber Bragg gratings. In some embodiments, the substrate is a stent positioned within a blood vessel. In some embodiments, the substrate is a membrane positioned on or wrapped around the outer diameter of a blood vessel. In some embodiments, the substrate comprises flexible or deformable materials chosen from the group consisting of: metals, metal alloys, stainless steel, nickel, nickel alloys, nickel titanium alloys, nitinol, cobalt-chromium alloys, silicone, polymers, polytetrafluoroethylene (PFTE), expanded PFTE (ePFTE), polylactide (PLA), ethylenevinyl acetate (EVA), polyurethane, poly-L-lactic acid (PLLA), poly(lactide-co-glycolic acid)) (PLGA), poly glycolic acid (PGA), polycarbonate, nylon, and any combinations thereof.

[0012] In some embodiments, the fiber optic sensor extends towards the surface of the skin and terminates at a distance of about 0.1 mm to about 10 mm from the skin surface. In some embodiments, the fiber optic sensor comprises at least one of: a receiver, a transmitter, and a transceiver. In some embodiments, the interrogator is configured to transmit a light signal to the sensor, and receive an emitted light signal from the sensor, wherein the light signals pass through skin and tissue. In some embodiments, the emitted light signal is a portion of the transmitted light signal reflected from the one or more reflective gratings. In some embodiments, the emitted light signal is a portion of the transmitted light signal passing through the one or more reflective gratings. In some embodiments, the emitted light signal has a shifted Bragg wavelength. In some embodiments, the shifted Bragg wavelength is proportional to the strain exerted on the sensor by the blood in the blood vessel. In some embodiments, the interrogator is configured to split the emitted light signal into a first portion and a second portion. In some embodiments, the first portion of the emitted light signal is directed to a first photodiode, and the second portion of the emitted light signal is directed to the second photodiode.

[0013] In some embodiments, the ratio of light intensities of the first and second portions of the emitted light signal is proportional to a shift in Bragg wavelength. In some embodiments, the emitted light signal is split via a beam splitter. In some embodiments, the second portion of the emitted light signal is filtered via an optical edge filter. In some embodiments, the interrogator splits and fdters the emitted light signal using an angled fdter or a photonic integrated circuit.

[0014] In some aspects, the present disclosure relates to an implantable hemodynamic monitoring system comprising a sensor comprising a substrate and a fiber optic connected to the substrate, the sensor configured to be implanted within a blood vessel, wherein the fiber optic comprises one or more reflective gratings, and an interrogator positioned on a skin surface at a position underlying the implantation site of the sensor, wherein the interrogator is configured to transmit a light signal to the sensor, and receive an emitted light signal from the sensor, the emitted light signal having a shifted Bragg wavelength, wherein the interrogator is configured to split the emitted light signal into a first portion and a second portion, wherein the interrogator is configured to filter the second portion of the emitted light signal.

[0015] In some embodiments, the implantable hemodynamic monitoring system further comprises a computing system communicatively connected to the interrogator and comprising a processor, a non-transitory computer readable medium, wherein the non- transitory computer readable medium contains instructions, which when executed by the processor, perform steps comprising: a) receiving one or more electrical signals indicative of the light intensities of the first and second portions of the emitted light signal, b) calculating a ratio of the light intensities of the first and second portions of the emitted light signal, and c) deriving a blood pressure measurement from the ratio of light intensities.

[0016] In some aspects, the present disclosure relates to a method of measuring blood pressure, comprising the steps of: providing a hemodynamic measurement system, implanting the sensor into a blood vessel of a subject, positioning the interrogator on a portion of the skin surface overlying the implant site of the sensor, transmitting a light signal from the interrogator to the sensor, receiving an emitted light signal from the sensor, wherein the emitted light signal has a shifted Bragg wavelength, calculating the shift in Bragg wavelength, and calculating a blood pressure based on the calculated shift in Bragg wavelength. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The following detailed description of embodiments of the invention will be better understood when read in conjunction with the appended drawings. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings.

[0018] Fig. 1 depicts a schematic of an exemplary hemodynamic monitoring system with an exemplary sensor and an exemplary wearable interrogator.

[0019] Fig. 2 depicts a schematic of an exemplary sensor configuration with the fiber-optic sensor connecting the receiver optics and emission optics.

[0020] Fig. 3 depicts a schematic showing two exemplary configurations of a hemodynamic monitoring system, wherein an exemplary sensor is implanted into a blood vessel and read by a wearable device (configuration 1) or by a device adhered to the skin (configuration 2).

[0021] Fig. 4A depicts a schematic showing fiber Bragg gratings in the exemplary sensor. Fig. 4B depicts a graph showing the shift in Bragg wavelength in the reflected and transmitted light signals through the fiber Bragg gratings. Strain can be sensed by analyzing either the reflected or transmitted spectrum.

[0022] Fig. 5A depicts an exemplary experimental setup to validate an exemplary Fiber-Bragg Grating (FBG) sensor against a conventional intra-arterial pressure sensor (IAP). Fig. 5B depicts a change in wavelength recorded by an exemplary FBG sensor and the pressure recorded by the conventional IAP sensor during a simulated heartbeat.

[0023] Fig. 6 depicts a graph showing transcutaneous optical coupling in reflection (top row) and transmission (bottom row) configurations.

[0024] Fig. 7A depicts graphs showing exemplary results of Bragg wavelength measurements in different types of tissue acquired via transcutaneous optical coupling, before applying a strain to the optical fiber sensor. Fig. 7B depicts graphs showing exemplary results of Bragg wavelength measurements in different types of tissue acquired via transcutaneous optical coupling, after applying a strain to the optical fiber sensor. Fig. 7C depicts graphs showing the shift in Bragg wavelength plotted against the normalized strain in different types of tissue. For each tissue, the Bragg wavelength shift is recorded via transcutaneous optical coupling with results indicating equivalence to a conventional direct wired connection.

[0025] Fig. 8A depicts a schematic of an exemplary optical interrogator using edge fdters. Fig. 8B depicts graphs showing the ratio of signal to reference and showing that the ratio is directly proportional to the blood pressure induced strain on the fiberoptic sensor. Fig. 8C depicts graphs showing that the signal to reference ratio remains independent of power loss which may arise for a variety of reasons including light-tissue interaction and misalignment of optics.

[0026] Fig. 9 depicts an exemplary computing environment in which aspects of the present invention may be practiced.

[0027] Fig. 10 depicts a flowchart showing an exemplary method of measuring blood pressure.

[0028] DETAILED DESCRIPTION

[0029] The following discussion omits or only briefly describes conventional features of hemodynamic monitoring devices and systems that are apparent to those skilled in the art. Those of ordinary skill in the pertinent arts may thus recognize that other elements may be desirable and / or necessary to implement the devices, systems, and / or methods described herein. It is noted that various embodiments are described in detail with reference to the drawings. Reference to these various embodiments does not limit the scope of the claims attached hereto. Additionally, any embodiments set forth in this specification are intended to be non-limiting and merely set forth some of the many possible implementations for the appended claims. Further, particular features described herein can be used in combination with other described features in each of the various possible combinations and permutations. As such, it is understood that this detailed description is exemplary and explanatory only and is not restrictive of the broad inventive concepts upon which the embodiments disclosed herein are based.

[0030] Unless otherwise specifically defined herein, all terms are to be given their broadest reasonable interpretation. This includes meanings implied from the specification as well as meanings understood by those skilled in the art and / or as defined in dictionaries, treatises, etc. It is noted that, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless otherwise specified. The term “includes” and / or “including,” when used in this specification, specify the presence of stated features, elements, and / or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof.

[0031] Relative terms such as “horizontal,” “vertical,” “up,” “down,” “top,” and “bottom” as well as derivatives thereof (e.g., “horizontally,” “downwardly,” “upwardly,” etc.) should be construed to refer to the orientation as then-described or as shown in the drawing figure under discussion. These relative terms are for convenience of description and normally are not intended to require a particular orientation in actuality. Terms including “inwardly” versus “outwardly,” “longitudinal” versus “lateral,” and the like are to be interpreted relative to one another or relative to an axis of elongation, or an axis or center of rotation, as appropriate. Terms concerning attachments, coupling and the like, such as “connected” and “interconnected,” refer to a relationship wherein structures are secured or attached to one another either directly or indirectly through intervening structures, as well as both movable or rigid attachments or relationships, unless expressly described otherwise. The phrases “operatively” or “operably connected” indicates such an attachment, coupling, or connection that allows the pertinent structures to operate as intended by virtue of that relationship.

[0032] Reference throughout the specification to “one embodiment,” “an embodiment,” or “some embodiments” means that a particular feature, structure, or characteristic described in connection with at least one embodiment of the subject matter is included in at least one embodiment of the subject matter disclosed. Thus, the appearance of the phrases “in one embodiment,” “in an embodiment,” or “in some embodiments” in various places throughout the specification is not necessarily referring to the same embodiment. Further, the particular features, structures, or characteristics of “one embodiment,” “an embodiment,” or “some embodiments” may be combined in any suitable manner with each other to form additional embodiments of such combinations. It is intended that embodiments of the disclosed subject matter cover modifications and variations thereof. Terms such as “first,” “second,” “third,” etc., merely identify one of a number of portions, components, steps, operations, functions, and / or points of reference as disclosed herein, and likewise to not necessarily limit embodiments of the present disclosure to any particular configuration or orientation.

[0033] Moreover, throughout this disclosure, various aspects can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, 6, and any whole and partial increments therebetween. This applies regardless of the breadth of the range. As used herein, the term “about” in reference to a measurable value, such as an amount, a temporal duration, and the like, is meant to encompass the specified value or variations of plus or minus 20%, plus or minus 10%, plus or minus 5%, plus or minus 1%, and plus or minus 0.1% of the specified value, as such variations are appropriate and fit within the confines of a functional system.

[0034] The terms “proximal,” “distal,” “anterior,” “posterior,” “medial,” “lateral,” “superior,” and “inferior” are defined by their standard usage indicating a directional term of reference. For example, “proximal” refers to a position that is situated nearer to the center of a body or point of attachment or interest. In another example, “anterior” refers to the front of a body or structure, while “posterior” refers to the rear of a body or structure, in relation to a relative viewpoint. In another example, “medial” refers to the direction towards the midline of a body or structure, and “lateral” refers to the direction away from the midline of a body or structure. In some examples, “lateral” or “laterally” may refer to any sideways direction. In another example, “superior” refers to the top of a body or structure, while “inferior” refers to the bottom of a body or structure. It should be understood, however, that the directional term of reference may be interpreted within the context of a specific body or structure, such that a directional term referring to a location in the context of the reference body or structure may remain consistent as the orientation of the body or structure changes.

[0035] The terms “patient,” “subject,” “individual,” and the like are used interchangeably herein, and refer to any animal amenable to the systems, devices, and methods described herein. The patient, subject or individual may be a mammal, and in some instances, a human.

[0036] In some aspects, the present disclosure relates to a hemodynamic monitoring system configured to continuously monitor the blood pressure of a subject. In some embodiments, the hemodynamic monitoring system is configured to acquire and / or display blood pressure measurements in real-time. In some embodiments, the hemodynamic monitoring system comprises a sensor implanted in a blood vessel of the subject, and an interrogator configured to transmit a light signal to the sensor and receive an emitted light signal from the sensor 102, wherein the emitted light signal has experienced a shift in Bragg wavelength. In some embodiments, the hemodynamic monitoring system is configured to measure the shift in Bragg wavelength in the emitted light signal, the shift in Bragg wavelength being indicative of a strain exerted on the sensor by the blood pressure in the vessel. In some embodiments, the hemodynamic monitoring system is configured to calculate a blood pressure measurement based on the shift in Bragg wavelength. In some embodiments, the subject may be a healthy patient or a patient suffering from hypertension, coronary heart disease, heart failure, or any other cardiovascular disease.

[0037] Referring now to Fig. 1, shown is an exemplary hemodynamic monitoring system 100 (hereinafter “system 100.”) The system 100 generally comprises a sensor 102 configured to be implanted in a blood vessel of a subject, and an interrogator 112 positioned on a portion of the skin surface overlying the implant site. In some embodiments, the interrogator 112 is configured to transmit a light signal to the sensor 102 via transcutaneous optical coupling, wherein the light signal passes through the skin and intermediary tissue to the sensor 102. In some embodiments, the interrogator 112 is configured to receive an emitted light signal from the sensor 102, via transcutaneous optical coupling. As used herein, the term “transcutaneous optical coupling” refers to wireless communication through the skin and tissue using optical signals. Referring now to Fig. 2, shown is an exemplary sensor 102. The sensor 102 generally comprises a substrate 104 and a fiber optic 106 mounted on or positioned within the substrate 104. In some embodiments, the fiber optic 106 comprises a receiver 108 configured to receive a light signal from the interrogator 112, and a transmitter 110 configured to transmit a light signal to the interrogator 112. In some embodiments, the fiber optic 106 further comprises one or more reflective gratings positioned within the core of the fiber optic 106. In some embodiments, the receiver 108 and transmitter 110 may include any optical element known to one of skill in the art, including but not limited to, prisms, conventional optical lenses, metalenses, angled fiber surfaces, photonic integrated circuits, vertical grating couplers, edge couplers, and the like. In some embodiments, the sensor 102 may further comprise one or more fiber optic leads, wherein at least a first fiber optic lead is configured to receive a light signal, and at least a second fiber optic lead is configured to transmit the light signal. In some embodiments, the fiber optic 106 is configured to both receive and transmit the light signal. In some embodiments, the light signal may be both received and transmitted from a single transceiver integrating both the receiver 108 and the transceiver 110.

[0038] In some embodiments, the substrate 104 is formed from an elastic, flexible, or distensible material, such that the blood pressure within a blood vessel exerts a measurable strain on the substrate 104. In some embodiments, the substrate 104 is formed as a stent, an endograft, or any other vascular implant as would be known by one of skill in the art. For example, the substrate may be a generally cylindrical or tubular structure formed of a mesh material and configured to be implanted within a blood vessel. In some embodiments, the substrate 104 may have any other shape suitable for interfacing with a blood vessel. For example, in some embodiments, the substrate 104 may have an annular or ring-shape configured to encircle the outer or inner diameters of a blood vessel. In some embodiments, the substrate 104 may be a membrane configured to rest on a region of the outer or inner surface of a blood vessel. In some embodiments, the substrate 104 may be formed from a mesh material comprising one or more interlacing wires or strands. Fig. 3 depicts exemplary configurations of the sensor 102.

[0039] In some embodiments, the substrate 104 may be formed from a biocompatible material. In some embodiments, the substrate 104 may be formed from of any flexible, elastic, deformable, or distensible material known to one in the art. In some embodiments, the substrate 104 may be formed from materials including, but not limited to, metals, metal alloys, stainless steel, nickel, nickel alloys, nickel titanium alloys, nitinol, cobalt-chromium alloys, silicone, polymers, polytetrafluoroethylene (PFTE), expanded PFTE (ePFTE), polylactide (PLA), ethylene-vinyl acetate (EVA), polyurethane, poly-L-lactic acid (PLLA), poly(lactide-co-glycolic acid)) (PLGA), poly glycolic acid (PGA), polycarbonate, nylon, or any combinations thereof.

[0040] In some embodiments, the substrate 104 may be sized to fit into an artery, a vein, a capillary, or any suitable shallow blood vessel. In some embodiments, the substrate 104 may have any suitable dimensions for insertion into a desired blood vessel. In some embodiments, the substrate 104 has a length ranging between about 1 mm and 100 mm, between about 5 mm and 95 mm, between about 10 mm and 90 mm, between about 15 mm and 85 mm, between about 20 mm and 80 mm, between about 25 mm and 75 mm, between about 30 mm and 70 mm , between about 35 mm and 65 mm, between about 40 mm and 60 mm, between about 45 mm and 55 mm, about 1 mm, about 5 mm, about 10 mm, about 20 mm, about 30 mm, about 40 mm, about 50 mm, about 60 mm, about 70 mm, about 80 mm, about 90 mm, or about 100 mm. In some embodiments, the substate 104 has a width or diameter of about 1 mm, about 5 mm, about 10 mm, about 20 mm, about 30 mm, about 40 mm, about 50 mm, about 60 mm, about 70 mm, about 80 mm, about 90 mm, about 100 mm, or ranging between about 1 mm and about 100 mm, between about 5 mm and 95 mm, between about 10 mm and 90 mm, between about 15 mm and 85 mm, between about 20 mm and 80 mm, between about 25 mm and 75 mm, between about 30 mm and 70 mm, between about 35 mm and 65 mm, between about 40 mm and 60 mm, or between about 45 mm and 55 mm. In some embodiments, one or more wires of the substrate 104 has a thickness or diameter ranging of about 0.0001 mm, about 0.001 mm, about 0.01 mm, about 0.1 mm, about 0.2 mm, about 0.3 mm, about 0.4 mm, about 0.5 mm, about 0.6 mm, about 0.7 mm, about 0.8 mm, about 0.9 mm, about 1 mm, about 1.5 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, or ranging between about 0.0001 mm and 5 mm, between about 0.001 mm and 4 mm, between about 0.01 mm and 3 mm, between about 0.1 mm and 2 mm, or between about 1 mm and 1.5 mm. It should be appreciated that the dimensions of the substrate 104 may be modified depending on the type and size of the blood vessel the sensor is implanted in. In some embodiments, the substrate 104 may be provided in a set of different sizes for implantation in blood vessels having different diameters.

[0041] In some embodiments, the fiber optic 106 may be fixedly attached to the substrate 104. In some embodiments, the fiber optic 106 may be attached to the substrate 104 via any method known to one of skill in the art, such that the mechanical strain on the substrate 104 may be transferred to the fiber optic 106 without significant losses or distortion. In some embodiments, the fiber optic 106 may be fixedly attached to the substrate 104 via glues, adhesives, epoxy, laser machining, welding, thermal bonding, soldering, mechanical clamping, UV-curable resins, ultrasonic welding, compression fitting, microfabricated retention structures, and the like, or any combinations thereof. In some embodiments, the fiber optic 106 is configured to receive a light signal via the receiver 108. In some embodiments, the sensor 102 is configured to transmit a light signal via the transmitter 110. In some embodiments, light signal travels through the core of the fiber optic 106 between the receiver 108 and the transmitter 110. In some embodiments, the fiber optic 106 may have a length ranging between about 1 mm and 100 mm, between about 5 mm and 95 mm, between about 10 mm and 90 mm, between about 15 mm and 85 mm, between about 20 mm and 80 mm, between about 25 mm and 75 mm, between about 30 mm and 70 mm , between about 35 mm and 65 mm, between about 40 mm and 60 mm, between about 45 mm and 55 mm, about 1 mm, about 5 mm, about 10 mm, about 20 mm, about 30 mm, about 40 mm, about 50 mm, about 60 mm, about 70 mm, about 80 mm, about 90 mm, or about 100 mm.

[0042] In some embodiments, the fiber optic 106 further comprises one or more reflective gratings positioned within the core of the fiber optic 106. In some embodiments, the one or more reflective gratings are Fiber Bragg gratings. In some embodiments, the Fiber Bragg gratings have a Bragg wavelength ranging between 600 nm and 2500 nm. In some embodiments, at least a portion of the light signal traveling through the fiber optic 106 is transmitted through the one or more reflective gratings. In some embodiments, at least a portion of the light signal travelling through the fiber optic 106 is reflected from the one or more reflective gratings. In some embodiments, the Fiber Bragg gratings have a reflectivity ranging between 5% and 100%. Fig. 4A depicts a schematic of exemplary Fiber Bragg gratings within the core of a fiber optic 106.

[0043] In some embodiments, the fiber optic 106 may extend a distance from the substrate 104 towards the surface of the skin. In some embodiments, the fiber optic 106 extends towards the surface of the skin such that the distance between the surface of the skin and fiber optic 106 ranges between about 0.1 mm to about 10 mm. In some embodiments, the sensor 102 may be implanted into shallow blood vessels (close to the skin surface) to limit the distance between the interrogator 112 and the sensor 102. It should be appreciated that although described herein as a fiber optic, the sensor 102 ma comprise any optical waveguide component configured to guide light or electromagnetic waves. For example, the sensor 102 may comprise optical fibers, integrated optical circuits, hollow metallic waveguides, dielectric waveguides, liquid waveguides, diffractive waveguides, or any other optical component configured to guide light through the sensor 102.

[0044] In some embodiments, the sensor 102 may comprise any other optical component known to one of skill in the art. In some embodiments, the sensor 102 may be implanted in any suitable blood vessel. In some embodiments, the blood vessel may be a shallow blood vessel, an artery, a vein, or a capillary. In some embodiments, the sensor 102 may include any other sensors known to one of skill in the art. For example, the sensor 102 may further include temperature sensors, displacement or position sensors, accelerometers, pressure sensors, oxygen saturation (SpCh) sensors, blood flow sensors, and the like, or any other combinations thereof. In some embodiments, a temperature sensor may be used for temperature compensation. In some embodiments, the temperature sensor may be configured as an additional fiber optic comprising Fiber Bragg gratings configured for temperature sensing. In some embodiments, the temperature sensor may be configured as separate Fiber Bragg gratings having a different Bragg wavelength integrated in the fiber optic 106. In some embodiments, the sensor 102 may be implanted using any method known to one of skill in the art. For example, a catheter may be used to implant the sensor 102 through an incision made on a patient’s skin. In some embodiments, the sensor 102 may be implanted with minimally invasive methods (e.g. percutaneously).

[0045] In some embodiments, the interrogator 112 is configured to wirelessly interface with the sensor 102 via transcutaneous optical coupling. In some embodiments, the interrogator 112 comprises a transmitter. In some embodiments, the interrogator 112 comprises a receiver. In some embodiments, the interrogator 112 comprises at least a first and a second photodiode. In some embodiments, the interrogator 112 comprises a beam splitter. In some embodiments, the interrogator 112 comprises an optical edge filter. In some embodiments, the interrogator may comprise any other optical element known to one of skill in the art, including but not limited to lenses, objectives, diffraction gratings, polarizers, high-pass filters, low-pass filters, band-pass filters, prisms, mirrors, fiberoptic splitters, fiber-optic couplers, fiber-optic circulators, Fiber-Bragg gratings, photonic integrated circuits including arrayed waveguide gratings and / or ring resonators for wavelength demultiplexing.

[0046] In some embodiments, the interrogator 112 is configured to transmit a light signal through the skin to the sensor 102 such that the light signal enters the fiber optic 106. In some embodiments, the light signal may have a wavelength or a range of wavelengths ranging between about 600 nm and 2500 nm. In some embodiments, the light signal may be a broadband or narrow near infrared spectrum. In some embodiments, the optical spectrum is created by synchronously or asynchronously emitting light from a series of light sources with different wavelength spectra. In some embodiments, the light source may be light emitting diodes, superluminescent diodes, laser diodes, lasers, vertical-cavity surface-emitting lasers, and the like.

[0047] In some embodiments, the interrogator 112 is configured to receive an emitted light signal from the sensor 102. It should be understood that the term “emitted light signal” may refer to either at least a portion of light that has been reflected from the one or more reflective gratings in the fiber optic 106, or at least a portion of light transmitted through the one or more reflective gratings in the fiber optic 106. In some embodiments, the interrogator 112 may be configured to receive the portion of reflected light, the portion of transmitted light, or a combination of both.

[0048] In some embodiments, the emitted light signal has a shifted Bragg wavelength. In some embodiments, the shift in Bragg wavelength is directly proportional to the strain experienced by the sensor 102 due to the blood pressure in the blood vessel. It should be appreciated that the shift in Bragg wavelength is independent of specific tissue optical properties, and is consistent across different tissue types. In some embodiments, a blood pressure measurement may be derived from a measured shift in Bragg wavelength. In some embodiments, the shift in the Bragg wavelength is determined via an analysis of optical power transmission.

[0049] In some embodiments, the emitted light signal received by the interrogator 112 passes through a beam splitter, thereby splitting the emitted light signal into a first portion and a second portion. In some embodiments, the first portion of light is directed to a first photodiode. In some embodiments, the second portion of light is directed to a second photodiode. In some embodiments, the second portion of light is filtered via an optical filter prior to being directed to the second photodiode. In some embodiments, the optical filter is an optical edge filter. In some embodiments, angled filters or photonic integrated circuits, or any other optical components may be used to both split the emitted light signal into the first and second portions and filter the second portion. In some embodiments, the first and second photodiodes are configured to measure the light intensities of the first and second portions of the emitted light signal. Fig. 8A depicts a schematic of an exemplary interrogator 112.

[0050] In some embodiments, a ratio of the light signal intensities of the first portion of light and the second portion of light may be calculated. In some embodiments, the ratio is directly proportional to a shift in the Bragg wavelength experienced by the emitted light signal. It should be appreciated that the ratio is independent of power loss induced by the variation in tissue optical properties, or potential misalignment of optical components, and may therefore be used across a broad population without the need for multiple calibrations. In some embodiments, the shift in the Bragg wavelength may be used to calculate a blood pressure measurement in the blood vessel. It should be appreciated that due to the mechanical configuration of the sensor 102, the strain experienced by the fiber optic 106 is proportional to the blood pressure, thereby enabling the calculation of blood pressure. In some embodiments, the blood pressure measurement may be one or more of: a systolic blood pressure, a diastolic blood pressure, a central blood pressure, a peripheral blood pressure, an ambulatory blood pressure, an arterial blood pressure, or a venous blood pressure.

[0051] In some embodiments, the system 100 further comprises a computing system 200 (as shown in Fig. 9) communicatively connected to the interrogator 112. In some embodiments, the computing system 200 comprises a processor, a non-transitory computer readable medium, wherein the non-transitory computer readable medium contains instructions, which when executed by the processor, perform steps comprising: a) receiving one or more electrical signals indicative of the light intensities of the first portion of the emitted light signal and the second portion of the emitted light signals, b) calculating a ratio of the light intensities of the first and second portions of the emitted light signal, and c) deriving a blood pressure measurement from the ratio of light intensities.

[0052] In some embodiments, the computing system 200 may be configured to repeat the steps a) to c) once every set duration of time. In some embodiments, the set duration of time may range between 10 ms second and 7 days. In some embodiments, the set duration of time may be modified according to the needs of each patient. In some embodiments, the set duration is cycled so as to acquire measurements periodically, for example every 10 ms, every 50 ms, every 100 ms, every 250 ms, every 500 ms, every second, every minute, every 10 minutes, every hour, every 2 hours, every 6 hours, every 12 hours, every day, every week, or any other suitable time period.

[0053] In some embodiments, the computing system 200 may be configured to receive data, measurements or calculations from the interrogator 112. In some embodiments, the computing system 200 may receive data as digital signals, analog signals, or both. The computing system 200 may be a smart device (e g. a smart watch), a handheld device (e.g. a smartphone), a wearable device, or any other device known to one of skill in the art. In some embodiments, the computing system 200 may comprise a display. In some embodiments, the computing system 200 may be configured to receive user input to such that the processor performs one or more of: initiating a blood pressure measurement, acquiring blood pressure measurements periodically at a user-determined frequency, displaying a blood pressure measurement, displaying a graphical representation of the blood pressure measurement, displaying previously acquired blood pressure measurements, transmitting blood pressure measurements to an external device. In some embodiments, the computing system 200 may further comprise stored instructions for performing analysis or display of the data collected. The data collected may be presented as raw data, a time series graph, a real-time display of current values, minimum or maximum values, average values, or any other display format known to one of skill in the art. In some embodiments, the computing system 200 may further include non-transitory computer readable media having calibration data for the sensor 102. For example, the computing system 200 may comprise temperature calibration data. In some embodiments, the computing system 200 may be configured for software-based temperature compensation during measurement. In some embodiments, the computing system 200 may connect to one or more external displays in a wired or wireless connection. In some embodiments, the computing system 200 may be communicatively connected to an interface device. In some embodiments, the interface device may be configured to transmit data or measurements to an external device. As described herein, “interface device” refers to any device capable of receiving analog or digital signals and performing one or more of: storing the data on a non-transitory computer readable medium or transmitting the data via a wired or wireless communication link to a remote computing device.

[0054] In some embodiments, the interrogator 112 and / or the computing system 200 may be integrated with a wearable device configured to be worn on any part of the body. Exemplary configurations of wearable devices are depicted in Fig. 3. In some embodiments, the wearable device may be configured to be worn on the wrist. For example, the interrogator 112 and / or the computing system 200 may be configured as a wristwatch, a smart watch and the like. In some embodiments, the interrogator 112 and / or the computing system 200 may be configured as a module, wherein the module is configured to be adhered to the skin. In some embodiments, the module may be adhered to the skin via adhesives, bio adhesives, tapes, films, patches, glues, gels, straps, bands, and the like, or any other method known to one of skill in the art. In some embodiments, the interrogator 112 and / or the computing system 200 may be integrated into a piece of clothing or an accessory worn on the body. In some embodiments, the interrogator 112 and / or the computing system 200 may be integrated with a handheld device, for example a smartphone, tablet, or any other device, configured to be temporarily positioned on a region of skin surface to obtain a blood pressure measurement. It should be understood that the interrogator must be placed as close as possible to the skin surface above the location in which the sensor 102 has been implanted so as to transmit and / or receive the signal from the sensor 102. In some embodiments, and as depicted in Fig. 3, the sensor 102 may be implanted in a radial artery such that the interrogator 112 and / or the computing system 200 is positioned on the wrist. In other embodiments, the sensor 102 may be implanted in the jugular vein, such that the interrogator 112 and / or the computing system 200 is positioned on the neck. In other examples, the sensor 102 may be implanted in any shallow blood vessel and the interrogator 112 and / or the computing system 200 is positioned at any location on the skin surface overlying the implant site of sensor 102.

[0055] In some aspects, the present disclosure relates to a method of obtaining a blood pressure measurement. Referring now to Fig. 10, shown is an exemplary method 300 of obtaining a blood pressure measurement. The method 300 generally comprises the steps of: providing a hemodynamic measurement system (e.g. system 100) (302), implanting a sensor (e.g. sensor 102) into a blood vessel of a subject (304), positioning a wearable interrogator (e.g. interrogator 112) on a portion of the skin surface overlying the implant site of the sensor (306), transmitting a light signal from the interrogator to the sensor (308), receiving an emitted light signal from the sensor, wherein the emitted light signal has a shifted Bragg wavelength (310), calculating the shift in Bragg wavelength (312), and calculating a blood pressure based on the calculated shift in Bragg wavelength (314).

[0056] In some embodiments, the method may further comprise splitting the emitted light signal into a first portion and a second portion and filtering the second portion of the emitted light signal. In some embodiments, the splitting and filtering step may be performed via a beam splitter and an optical edge filter, an angled filter, or a photonic integrated circuit. In some embodiments, the method may further comprise measuring the light intensities of the first and second portions of the emitted light signal. In some embodiments, the method may further comprise deriving a ratio of the light intensities of the first and second portions of the emitted light signal, wherein the ratio is indicative of a shift in the Bragg wavelength.

[0057] In some aspects of the present invention, software executing the instructions provided herein may be stored on a non-transitory computer-readable medium, wherein the software performs some or all of the steps of the present invention when executed on a processor.

[0058] Aspects of the invention relate to algorithms executed in computer software. Though certain embodiments may be described as written in particular programming languages, or executed on particular operating systems or computing platforms, it is understood that the system and method of the present invention is not limited to any particular computing language, platform, or combination thereof. Software executing the algorithms described herein may be written in any programming language known in the art, compiled, or interpreted, including but not limited to C, C++, C#, Objective-C, Java, JavaScript, MATLAB, Python, PHP, Perl, Ruby, or Visual Basic. It is further understood that elements of the present invention may be executed on any acceptable computing platform, including but not limited to a server, a cloud instance, a workstation, a thin client, a mobile device, an embedded microcontroller, a television, or any other suitable computing device known in the art.

[0059] Parts of this invention are described as software running on a computing device. Though software described herein may be disclosed as operating on one particular computing device (e.g. a dedicated server or a workstation), it is understood in the art that software is intrinsically portable and that most software running on a dedicated server may also be run, for the purposes of the present invention, on any of a wide range of devices including desktop or mobile devices, laptops, tablets, smartphones, watches, wearable electronics or other wireless digital / cellular phones, televisions, cloud instances, embedded microcontrollers, thin client devices, or any other suitable computing device known in the art.

[0060] Similarly, parts of this invention are described as communicating over a variety of wireless or wired computer networks. For the purposes of this invention, the words “network”, “networked”, and “networking” are understood to encompass wired Ethernet, fiber optic connections, wireless connections including any of the various 802.11 standards, cellular WAN infrastructures such as 3G, 4G / LTE, or 5G networks, Bluetooth®, Bluetooth® Low Energy (BLE) or Zigbee® communication links, or any other method by which one electronic device is capable of communicating with another. In some embodiments, elements of the networked portion of the invention may be implemented over a Virtual Private Network (VPN).

[0061] Fig. 9 and the following discussion are intended to provide a brief, general description of a suitable computing environment in which the invention may be implemented. While the invention is described above in the general context of program modules that execute in conjunction with an application program that runs on an operating system on a computer, those skilled in the art will recognize that the invention may also be implemented in combination with other program modules.

[0062] Generally, program modules include routines, programs, components, data structures, and other types of structures that perform particular tasks or implement particular abstract data types. Moreover, those skilled in the art will appreciate that the invention may be practiced with other computer system configurations, including handheld devices, multiprocessor systems, microprocessor-based or programmable consumer electronics, minicomputers, mainframe computers, and the like. The invention may also be practiced in distributed computing environments where tasks are performed by remote processing devices that are linked through a communications network. In a distributed computing environment, program modules may be located in both local and remote memory storage devices.

[0063] Fig. 9 depicts an illustrative computer architecture for a computer 200 for practicing the various embodiments of the invention. The computer architecture shown in Fig. 9 illustrates a conventional personal computer, including a central processing unit 250 (“CPU”), a system memory 205, including a random access memory 210 (“RAM”) and a read-only memory (“ROM”) 215, and a system bus 235 that couples the system memory 205 to the CPU 250. A basic input / output system containing the basic routines that help to transfer information between elements within the computer, such as during startup, is stored in the ROM 215. The computer 200 further includes a storage device 220 for storing an operating system 225, application / program 230, and data.

[0064] The storage device 220 is connected to the CPU 250 through a storage controller (not shown) connected to the bus 235. The storage device 220 and its associated computer-readable media provide non-volatile storage for the computer 200. Although the description of computer-readable media contained herein refers to a storage device, such as a hard disk or CD-ROM drive, it should be appreciated by those skilled in the art that computer-readable media can be any available media that can be accessed by the computer 200.

[0065] By way of example, and not to be limiting, computer-readable media may comprise computer storage media. Computer storage media includes volatile and nonvolatile, removable and non-removable media implemented in any method or technology for storage of information such as computer-readable instructions, data structures, program modules or other data. Computer storage media includes, but is not limited to, RAM, ROM, EPROM, EEPROM, flash memory or other solid state memory technology, CD-ROM, DVD, or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to store the desired information and which can be accessed by the computer.

[0066] According to various embodiments of the invention, the computer 200 may operate in a networked environment using logical connections to remote computers through a network 240, such as TCP / IP network such as the Internet or an intranet. The computer 200 may connect to the network 240 through a network interface unit 245 connected to the bus 235. It should be appreciated that the network interface unit 245 may also be utilized to connect to other types of networks and remote computer systems.

[0067] The computer 200 may also include an input / output controller 255 for receiving and processing input from a number of input / output devices 260, including a keyboard, a mouse, a touchscreen, a camera, a microphone, a controller, a joystick, or other type of input device. Similarly, the input / output controller 255 may provide output to a display screen, a printer, a speaker, or other type of output device. The computer 200 can connect to the input / output device 260 via a wired connection including, but not limited to, fiber optic, Ethernet, or copper wire or wireless means including, but not limited to, Wi-Fi, Bluetooth, Near-Field Communication (NFC), infrared, or other suitable wired or wireless connections.

[0068] As mentioned briefly above, a number of program modules and data files may be stored in the storage device 220 and / or RAM 210 of the computer 200, including an operating system 225 suitable for controlling the operation of a networked computer. The storage device 220 and RAM 210 may also store one or more applications / programs 230. In particular, the storage device 220 and RAM 210 may store an application / program 230 for providing a variety of functionalities to a user. For instance, the application / program 230 may comprise many types of programs such as a word processing application, a spreadsheet application, a desktop publishing application, a database application, a gaming application, internet browsing application, electronic mail application, messaging application, and the like. According to an embodiment of the present invention, the application / program 230 comprises a multiple functionality software application for providing word processing functionality, slide presentation functionality, spreadsheet functionality, database functionality and the like.

[0069] The computer 200 in some embodiments can include a variety of sensors 265 for monitoring the environment surrounding and the environment internal to the computer 200. These sensors 265 can include a Global Positioning System (GPS) sensor, a photosensitive sensor, a gyroscope, a magnetometer, thermometer, a proximity sensor, an accelerometer, a microphone, biometric sensor, barometer, humidity sensor, radiation sensor, or any other suitable sensor.

[0070] EXPERIMENTAL EXAMPLES

[0071] The invention is further described in detail by reference to the following experimental examples. These examples are provided for purposes of illustration only, and are not intended to be limiting unless otherwise specified. Thus, the invention should in no way be construed as being limited to the following examples, but rather, should be construed to encompass any and all variations which become evident as a result of the teaching provided herein.

[0072] Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the present invention and practice the claimed methods. The following working examples therefore are not to be construed as limiting in any way the remainder of the disclosure.

[0073] Example 1 : Implantable Fiber-Optic Sensor The hemodynamic monitoring system consists of two components: 1) an implantable fiber-optic based sensor, and 2) a wearable optical interrogator as illustrated in Fig 3. The implantable sensor is inserted into a shallow blood vessel and the pressure within the vessel is determined via wireless transcutaneous optical coupling with the wearable. The sensor may be integrated into a stent and positioned in the radial artery where it is continuously interrogated by a wearable in a watch-type form factor. The sensor may be positioned in a jugular vein and interrogated via a wearable device adhered to the skin immediately above the sensor. This approach enables measurement of right atrial filling pressure and central venous pressure which are valuable metrics for monitoring fluid status in heart failure patients. Alternatively, the interrogator consists of a handheld or other portable device instead of a wearable. These examples illustrate potential configurations but are not intended to be limiting.

[0074] The pressure sensor utilizes fiber-Bragg gratings (FBG) which measure pressure induced strain within the optical fiber. Briefly, when light is injected into the fiber a narrow spectrum reflects off the FBG. The center wavelength of this spectrum, the Bragg wavelength, is dependent on the strain experienced by the fiber (Figs. 4A and 4B). The blood pressure induces strain on the fiber and thus it can be inferred by recording either the transmitted or reflected wavelength spectra using an optical interrogator.

[0075] The optical fiber is mounted directly on a conventional stent (e.g. nitinol or other relatively flexible material) and measures the strain experienced by the stent as it expands and contracts due to hemodynamic forces (Fig. 2). The fiber optic may also be placed on a membrane covering a cavity or a membrane encircling the stent. The membrane may also be wrapped around the outside of the blood vessel as shown in Fig. 5 A. Here, the sensor is tested by simulating hemodynamics via a custom-built pumping platform and synthetic blood vessel. Pressure within the blood vessel is recorded simultaneously via a conventional intra-arterial pressure sensor and the fiber-optic sensor. The functionality of the optical sensor is clearly illustrated as the change in the Bragg wavelength (AX) matches the output of the conventional intra-arterial pressure sensor (Fig. 5B).

[0076] Example 2: Optical Interrogator and Transcutaneous Optical Coupling The key aspect is the wireless interface between the external interrogator and the implanted sensor via “Transcutaneous Optical Coupling”. Blood pressure causes a strain on the implanted sensor which in turn alters the FBG reflected wavelength (FBG shift). The sensor itself contains no electronics, instead the FBG shift is determined by transmitting light through the skin and into the implanted optical fiber with the reflected or transmitted spectrum returned through the skin and analyzed by the external interrogator which may be in a watch-style or other form factor (Fig. 1). The external interrogator uses multiple separate source and detecting fibers, or a single fiber may be used.

[0077] Example 3 : Principle of Operation

[0078] Light interaction with tissue is a complex process whereby photons can either reflect off the surface or penetrate into the tissue where they undergo multiple scattering events. Some photons will be absorbed by the tissue and converted to heat. (Niemz, M. H. Interaction Mechanisms. In Laser-Tissue Interactions: Fundamentals and Applications 58-88 (Springer, 2007).) Other photons will exit the tissue either on the same side as the light source or via transmission through the entire sample. It is well known that this process is wavelength dependent with near infrared light routinely used in medical sensing as it enables deep penetration. (Geoghegan, R. et al. IEEE Trans. Biomed. Eng. 69, 2545-2556 (2022).; Geoghegan, R. et al. Proc. Annu. Int. Conf. IEEE Eng. Med. Biol. Soc. EMBS 2020-July, 5272-5275 (2020).; Geoghegan, R, et al. IEEE Sensors Journal (2024).) Additionally, optical penetration depends on the content of the material through which light is passing. In light-tissue interaction the density of chromophores (e.g. melanin, water, blood) and optical scattering objects (e.g. collagen) greatly influences optical transmission. Consequently, optical measurements routinely require calibration for individual users. Here, a method of measuring blood pressure is presented that does not require such calibration as pressure is inferred from the shift in the Bragg wavelength rather than changes in reflected optical intensity. As illustrated in Fig. 6 (top row), the external interrogator irradiates the skin with a relatively broadband near infrared optical spectrum. The light travels through the tissue and enters the implant where a section of the spectrum reflects off the FBG within the optical fiber. The reflected spectrum returns through the tissue and is measured by the external interrogator. Each time light passes through the tissue, a portion of the power is absorbed and scattered thus the total optical power received by the interrogator is greatly influenced by user specific tissue optical properties and the alignment of the optics (external interrogator and implant). However, the shift in the Bragg wavelength (induced by blood pressure causing fiber-optic strain) is independent of tissue properties and thus provides a robust method of measuring blood pressure regardless of changes in total power transmitted. In one embodiment the shift in Bragg wavelength is determined by the analysis of light reflected off the FBG (Fig. 6 - top row). In a further embodiment, the shift in Bragg wavelength is determined by analyzing the light transmitted through the FBG (Fig. 6 - bottom row).

[0079] An example of the transmission configuration is shown in Figs. 7A - 7C where the total transmitted power varies depending on the tissue type but the shift in the Bragg wavelength is independent with a consistent strain induced shift observed across tissue types (Figs. 7A and 7B). This ensures that there is a consistent relationship between the strain experienced by the fiber-optic sensor and the shift in Bragg wavelength (Fig. 7C). Moreover, the shift measured using Transcutaneous Optical Coupling between sensor and interrogator matches the FBG shift acquired when directly connecting (wired) the sensor to a conventional commercial FBG interrogator. This further demonstrates that transmitting light through tissue does not interfere with accurate measurement of the Bragg wavelength shift.

[0080] Example 4: Pressure Measurement via Optical Power Analysis

[0081] Blood pressure is inferred by measuring strain induced changes in the Bragg wavelength (FBG shift). The FBG shift may be measured with a conventional optical spectrum analyzer or may be inferred based on analysis of optical power transmission. This approach is advantageous as it greatly reduces the size, complexity and cost of the interrogator unit. Here, the interrogator unit consists of a beam splitter, an edge filter and two photodiodes as shown in Fig. 8A. The optical interrogator captures light emitted from the implanted fiber -optic sensor once it has passed back through the skin (Fig. 8A). A portion of this detected light is directed by the beam splitter directly to a photodiode (Fig. 8A). This photodiode measurement is defined as the “reference”. The remaining light is directed by the beam splitter through an optical edge fdter to a second photodiode (Fig. 8A). This photodiode measurement is termed “signal”. The ratio between the reference and signal is directly proportional to the Bragg wavelength and thus strain experienced by the fiber-optic sensor when placed in a blood vessel (Fig. 8B). This ratio is independent of power loss induced by variation in tissue optical properties and / or misalignment of optics (Fig. 8C). It can therefore be used across a broad population without the need for multiple calibrations. Due to the mechanical configuration of the fiber-optic sensor, on a membrane / stent / substrate within the blood vessel or wrapped around the outer wall (Figs. 1 - 3), the strain experienced by the fiber optic is proportional to the blood pressure enabling final calculation of blood pressure. The optical components described here are sufficient for splitting and filtering light. Additionally beam splitting and filtering may be performed by a single angled filter instead of sperate components or may be performed by a photonic integrated circuit.

[0082] References

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[0102] The disclosures of each and every patent, patent application, and publication cited herein are hereby each incorporated herein by reference in their entirety. While this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by others skilled in the art without departing from the true spirit and scope of the invention. The appended claims are intended to be construed to include all such embodiments and equivalent variations.

Claims

1. CLAIMSWhat is claimed is:

1. An implantable hemodynamic monitoring system comprising: a sensor comprising a substrate and a fiber optic connected to the substrate, the sensor configured to be implanted within a blood vessel; wherein the fiber optic comprises one or more reflective gratings; and an interrogator positioned on a skin surface at a position underlying the implantation site of the sensor.

2. The hemodynamic monitoring system of claim 1, wherein the interrogator is integrated into a wearable device.

3. The hemodynamic monitoring system of claim 1, wherein the interrogator is integrated into a module, wherein the module is configured to be adhered to the skin.

4. The hemodynamic monitoring system of claim 1, wherein the interrogator is integrated into a handheld device.

5. The hemodynamic monitoring system of claim 1, wherein the one or more reflective gratings are Fiber Bragg gratings.

6. The hemodynamic monitoring system of claim 1, wherein the substrate is a stent positioned within a blood vessel.

7. The hemodynamic monitoring system of claim 1, wherein the substrate is a membrane positioned on or wrapped around the outer diameter of a blood vessel.

8. The hemodynamic monitoring system of claim 1, wherein the substrate comprises flexible or deformable materials chosen from the group consisting of: metals, metal alloys, stainless steel, nickel, nickel alloys, nickel titanium alloys, nitinol, cobalt-chromium alloys, silicone, polymers, polytetrafluoroethylene (PFTE), expanded PFTE (ePFTE), polylactide (PLA), ethylene-vinyl acetate (EVA), polyurethane, poly-L-lactic acid (PLLA), poly(lactide-co-glycolic acid)) (PLGA), poly glycolic acid (PGA), polycarbonate, nylon, and any combinations thereof.

9. The hemodynamic monitoring system of claim 1, wherein the fiber optic sensor extends towards the surface of the skin and terminates at a distance of about 0.1 mm to about 10 mm from the skin surface.

10. The hemodynamic monitoring system of claim 1 , wherein the fiber optic sensor comprises at least one of: a receiver, a transmitter, and a transceiver.

11. The hemodynamic monitoring system of claim 1, wherein the interrogator is configured to transmit a light signal to the sensor, and receive an emitted light signal from the sensor, wherein the light signals pass through skin and tissue.

12. The hemodynamic monitoring system of claim 1 1, wherein the emitted light signal is a portion of the transmitted light signal reflected from the one or more reflective gratings.

13. The hemodynamic monitoring system of claim 11, wherein the emitted light signal is a portion of the transmitted light signal passing through the one or more reflective gratings.

14. The hemodynamic monitoring system of claim 11, wherein the emitted light signal has a shifted Bragg wavelength.

15. The hemodynamic monitoring system of claim 14, wherein the shifted Bragg wavelength is proportional to the strain exerted on the sensor by the blood in the blood vessel.

16. The hemodynamic monitoring system of claim 11, wherein the interrogator is configured to split the emitted light signal into a first portion and a second portion.

17. The hemodynamic monitoring system of claim 16, wherein the first portion of the emitted light signal is directed to a first photodiode, and the second portion of the emitted light signal is directed to the second photodiode.

18. The hemodynamic monitoring system of claim 17, wherein the ratio of light intensities of the first and second portions of the emitted light signal is proportional to a shift in Bragg wavelength.

19. The hemodynamic monitoring system of claim 16, wherein the emitted light signal is split via a beam splitter.

20. The hemodynamic monitoring system of claim 16, wherein the second portion of the emitted light signal is filtered via an optical edge filter.21 . The hemodynamic monitoring system of claim 20, wherein the interrogator splits and filters the emitted light signal using an angled filter or a photonic integrated circuit.

22. An implantable hemodynamic monitoring system comprising: a sensor comprising a substrate and a fiber optic connected to the substrate, the sensor configured to be implanted within a blood vessel; wherein the fiber optic comprises one or more reflective gratings; and an interrogator positioned on a skin surface at a position underlying the implantation site of the sensor; wherein the interrogator is configured to transmit a light signal to the sensor, and receive an emitted light signal from the sensor, the emitted light signal having a shifted Bragg wavelength; wherein the interrogator is configured to split the emitted light signal into a first portion and a second portion; wherein the interrogator is configured to filter the second portion of the emitted light signal.

23. The hemodynamic monitoring system of claim 20, further comprising a computing system communicatively connected to the interrogator and comprising a processor, a non-transitory computer readable medium, wherein the non-transitory computer readable medium contains instructions, which when executed by the processor, perform steps comprising: a) receiving one or more electrical signals indicative of the light intensities of the first and second portions of the emitted light signal; b) calculating a ratio of the light intensities of the first and second portions of the emitted light signal; and c) deriving a blood pressure measurement from the ratio of light intensities.

24. A method of measuring blood pressure, comprising the steps of: providing the hemodynamic measurement system of claim 1; implanting the sensor into a blood vessel of a subject; positioning the interrogator on a portion of the skin surface overlying the implant site of the sensor; transmitting a light signal from the interrogator to the sensor; receiving an emitted light signal from the sensor, wherein the emitted light signal has a shifted Bragg wavelength; calculating the shift in Bragg wavelength; and calculating a blood pressure based on the calculated shift in Bragg wavelength.

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