High-throughput myocardial tissue mu n-level contractility fiber bragg grating sensor and detection method

Abstract

The application discloses a kind of high-flux myocardial tissue μN level contractility fiber grating sensors, it is characterized in that, including several sensing units, each sensing unit includes pedestal and fiber segment, the fiber segment between different sensing units is sequentially connected in head and tail;Wherein the pedestal is hollow structure, the both ends of fiber segment are fixed to the side of pedestal, the middle part of fiber segment is fixed to the other side of pedestal, so that the part of fiber segment passing through the hollow area of pedestal forms a pair of parallel suspended intervals;Fiber grating is provided on the suspended interval of one side of fiber segment, the radius of the suspended interval of fiber grating in fiber segment is less than the radius of the rest of fiber segment, fiber grating is provided with first grid area and second grid area, and the radius of first grid area and second grid area is not identical.The sensor can realize real-time distributed monitoring of myocardial tissue, and can realize temperature self-compensation, simple structure, high precision.

Description

Technical Field

[0001] This invention relates to the field of biosensor technology, specifically to a fiber optic grating sensor and detection method for high-throughput myocardial tissue μN-level contractile force. Background Technology

[0002] Cardiac cardiomyocytes possess the ability to contract upon excitation, and this contractility is crucial for pumping sufficient oxygen-rich blood from the heart to other organs and tissues. Abnormal myocardial contraction can lead to diseases such as heart failure, atrial fibrillation, and structural mutations in the myocardium. Therefore, measuring the contractile capacity of myocardial tissue is of great value in exploring the pathogenesis of cardiac diseases and quantifying the efficacy of drugs. Currently, atomic force microscopy, microcantilever beams, and elastic membranes are commonly used techniques to measure the micro-contractile force of myocardial tissue.

[0003] Atomic force microscopy can detect forces over a wide range from pN to μN, but it requires direct contact with cells to detect cell contractile forces, which can mechanically stimulate the cells and makes it unsuitable for long-term and high-throughput detection.

[0004] Microcantilever beam-based detection technology directly or indirectly detects tissue contractile force by measuring the deformation and displacement of the cantilever beam. However, the manufacturing technology for microcantilever beams is complex and requires high precision. During the detection process, the displacement of the microcantilever beam generally relies on image recognition and processing technology, which reduces the reliability of the detection results. Furthermore, this technology struggles to achieve real-time detection of the contractile force of cells and tissues with autonomous contractile capabilities, such as myocardium.

[0005] Elastic membrane detection technology measures contractile force by measuring changes in parameters such as strain and resistance of the membrane substrate. When a monolayer of cells implanted on an elastic membrane vibrates, it causes the membrane to bend, resulting in changes in the membrane's strain and resistance. However, this detection technology has difficulty in detecting the contractile force of three-dimensional cell tissues that conform to the in vivo environment. Summary of the Invention

[0006] The purpose of this invention is to provide a fiber optic grating sensor and detection method for high-throughput myocardial tissue μN-level contractile force, so as to realize long-term, high-throughput distributed real-time monitoring of myocardial tissue.

[0007] To solve the above-mentioned technical problems, the present invention provides a technical solution: a fiber optic grating sensor for high-throughput myocardial tissue μN-level contractile force, comprising a plurality of sensing units connected in series by optical fibers, one end of which is connected to an external demodulator, and each sensing unit is used to measure the contractile force generated by in vitro cultured myocardial tissue.

[0008] Each sensing unit includes a base and an optical fiber segment; the base is a hollow structure, the two ends of the optical fiber segment are fixed to one side of the base, and the middle part of the optical fiber segment is fixed to the other side of the base, so that the part of the optical fiber segment passing through the hollow area of ​​the base forms a pair of parallel suspension intervals; a fiber grating is provided on one side of the suspension interval of the optical fiber segment, the radius of the suspension interval with the fiber grating in the optical fiber segment is smaller than the radius of the rest of the optical fiber segment, the fiber grating has a first grating area and a second grating area, and the radii of the first grating area and the second grating area are different.

[0009] According to the above scheme, different sensing units are arranged horizontally adjacent to each other in a direction perpendicular to the suspension interval of the optical fiber segment; the optical fiber is reciprocated on the base of each sensing unit to form each optical fiber segment.

[0010] According to the above scheme, positioning bosses are provided on both sides of the base, and the optical fiber is fixed to the base by being wound and bonded to the side of the positioning bosses.

[0011] According to the above scheme, the positioning boss includes a square boss and a semi-circular boss. The square boss is disposed on the base of the sensing unit at the beginning and end and is used to fix the beginning and end of the optical fiber passing through the sensing unit. The semi-circular boss is used to fix the turning area of ​​the optical fiber.

[0012] According to the above scheme, the first and second gate areas have the same length.

[0013] According to the above scheme, the base is made of quartz glass.

[0014] According to the above scheme, the minimum bending radius of the optical fiber is greater than 4mm.

[0015] A high-throughput myocardial tissue μN-level contractile force monitoring system includes a fiber Bragg grating sensor, a demodulator, and a host computer, as described above. The fiber segment of the fiber Bragg grating sensor is connected to the demodulator, and the demodulator is electrically connected to the host computer.

[0016] A method for monitoring high-throughput myocardial tissue μN-level contractile force using the high-throughput myocardial tissue μN-level contractile force monitoring system described above is proposed. In this method, the two ends of the myocardial tissue to be tested are cultured and grown on a pair of suspension intervals of a certain sensing unit. All sensing units synchronously monitor the myocardial tissue cultured therein. When the myocardial tissue generates micro-contraction force, it pulls on the suspension interval, causing the fiber grating to deform and thus shifting the center wavelength of the fiber grating. The demodulator and the host computer calculate based on the center wavelength shift of each fiber grating, thereby synchronously and in real time monitoring the contraction of each myocardial tissue.

[0017] According to the above scheme, the specific calculation process of the demodulator and the host computer is as follows.

[0018] The suspension section equipped with a fiber optic grating is defined as the measurement suspension section, and the contact point between the myocardial tissue and the measurement suspension section is defined as the measured force point. In the initial state, the distance from the measured force point to the end of the measurement suspension section on the side with the fiber optic grating is L1, the distance from the measured force point to the end of the measurement suspension section on the side without the fiber optic grating is L2, the radius of the first grating area is R1, and the radius of the second grating area is R2.

[0019] When the myocardial tissue generates a micro-contraction force F, the axial force generated in the suspension interval is F. t Therefore, the deformations ΔL1 and ΔL2 of the suspension section, divided into two parts by the force-bearing point, are respectively:

[0020]

[0021] Where a is the length of the fiber grating, E is the elastic modulus of the fiber, and A1 and A2 are the cross-sectional areas of the first and second grating regions, respectively.

[0022] The force analysis of the direction perpendicular to the axis of the suspension section in the initial state yielded the following results.

[0023] Fcosθ=(F0+F t (sinα+sinβ)

[0024] Since θ is close to 0, we can assume that the direction of F is perpendicular to the axis of the suspension interval in the initial state. Therefore, we have:

[0025]

[0026] Therefore,

[0027]

[0028] For any point F in the above equation t0 Performing a Taylor series expansion at the given point, and ignoring expansion terms of order two or higher, the above equation transforms into:

[0029] F = F(F) t0 +F'(F t0 (F) t -F t0 )

[0030] in,

[0031]

[0032] Therefore,

[0033] F = F(F) t0 )+F'(F t0 (F) t -F t0)=F'(F t0 )F t +(F(F t0 )-F t0 F'(F t0 ))=K1F t +K2

[0034] In the above formula, K1 and K2 are constant coefficients determined by the structural configuration parameters of the fiber Bragg grating sensor;

[0035] The center wavelength shift Δλ' of the first and second gate regions B1 ,Δλ' B2 Represented as,

[0036]

[0037]

[0038] In the above formula, ρ e λ is the optical elastic coefficient of the optical fiber. B1 , λ B2 These are the initial center wavelengths of the first and second grating regions, respectively;

[0039] The relationship between the center wavelength drift of a fiber Bragg grating and the forces and temperatures it experiences is as follows:

[0040]

[0041] Where ζ is the thermo-optic coefficient of the optical fiber, σ is the linear thermal expansion coefficient of the optical fiber, and ΔT is the temperature change.

[0042] The beneficial effects of this invention are:

[0043] 1. Micro-contraction force of myocardial tissue is detected by setting up a suspension section with a fiber Bragg grating. This eliminates the need for active stimulation of the myocardial tissue and uses optical signals for data transmission, resulting in high real-time performance and immunity to electromagnetic interference. The radius of the suspension section with the fiber Bragg grating is smaller than the radius of the rest of the fiber segment; this diameter reduction further improves measurement sensitivity. Self-compensation for ambient temperature errors is achieved by setting first and second grating regions with different radii on the fiber Bragg grating. Multiple sensing units measure different myocardial tissues individually, enabling distributed monitoring of the contractile force of multiple myocardial tissues.

[0044] 2. By setting a semi-circular boss, the optical fiber is bent horizontally between different sensing units, and the spacing between different sensing units and the degree of bending of the optical fiber can be adjusted by adjusting the width of the semi-circular boss.

[0045] 3. By using a quartz glass support base, the fiber optic grating sensor has good biocompatibility. Attached Figure Description

[0046] Figure 1 This is a structural diagram of a fiber optic grating sensor with a single sensing unit according to an embodiment of the present invention;

[0047] Figure 2 This is a structural diagram of a fiber optic grating sensor with multiple sensing units according to an embodiment of the present invention;

[0048] Figure 3 This is a schematic diagram of the grating region of a fiber Bragg grating according to an embodiment of the present invention;

[0049] Figure 4 This is a schematic diagram of the force analysis of the suspension section subjected to the micro-contraction force of myocardial tissue according to an embodiment of the present invention.

[0050] In the diagram: 1-optical fiber, 2-base, 3-fiber grating, 4-myocardial tissue, 5-square boss, 6-semi-circular boss, 301-first grating region, 302-second grating region. Detailed Implementation

[0051] To make the objectives, technical solutions, and advantages of the embodiments of this disclosure clearer, the technical solutions of the embodiments of this disclosure will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this disclosure. All other embodiments obtained by those skilled in the art based on the described embodiments of this disclosure without creative effort are within the scope of protection of this disclosure.

[0052] See Figures 1-3 A high-throughput fiber Bragg grating sensor for μN-level contractile force of myocardial tissue includes several sensing units. Each sensing unit includes a base 2 and an optical fiber segment. The optical fiber segments of different sensing units are connected end to end in sequence. The base 2 is a hollow structure. The two ends of the optical fiber segment are fixed to one side of the base 2, and the middle part of the optical fiber segment is fixed to the other side of the base 2, so that the part of the optical fiber segment passing through the hollow area of ​​the base 2 forms a pair of parallel suspension intervals. A fiber Bragg grating 3 is provided on the suspension interval on one side of the optical fiber segment. The radius of the suspension interval with the fiber Bragg grating 3 in the optical fiber segment is smaller than the radius of the rest of the optical fiber segment, and all suspension intervals with the fiber Bragg grating 3 are located on the same side of the base 2. The fiber Bragg grating 3 has a first grating region 301 and a second grating region 302, and the radii of the first grating region 301 and the second grating region 302 are different.

[0053] Furthermore, different sensing units are arranged horizontally adjacent to each other in a direction perpendicular to the suspension interval of the optical fiber segment; optical fiber 1 is reciprocated on the base 2 of each sensing unit to form each optical fiber segment.

[0054] Furthermore, positioning bosses are provided on both sides of the base 2, and the optical fiber 1 is fixed to the base 2 by being wound and bonded to the side of the positioning bosses.

[0055] Furthermore, the positioning boss includes a square boss 5 and a semi-circular boss 6. The square boss 5 is disposed on the base 2 of the sensing unit at the beginning and end and is used to fix the beginning and end of the optical fiber 1 passing through the sensing unit. The semi-circular boss 6 is used to fix the turning area of ​​the optical fiber 1. The spacing between the paired suspension intervals can be determined by the different widths of the semi-circular boss 6, and the bending radius of the optical fiber 1 can be controlled.

[0056] Furthermore, the first gate region 301 and the second gate region 302 have the same length.

[0057] Furthermore, the base 2 is made of quartz glass to improve the biocompatibility of the fiber Bragg grating sensor.

[0058] Furthermore, the minimum bending radius of optical fiber 1 is greater than 4 mm to ensure that the sensing loss of optical fiber 1 is below a certain value.

[0059] A high-throughput myocardial tissue μN-level contractile force monitoring system includes a fiber Bragg grating sensor, a demodulator, and a host computer, as described above. The fiber segment of the fiber Bragg grating sensor is connected to the demodulator, and the demodulator is electrically connected to the host computer.

[0060] A method for monitoring high-throughput myocardial tissue μN-level contractile force using the high-throughput myocardial tissue μN-level contractile force monitoring system described above is disclosed. In this method, the two ends of the myocardial tissue 4 to be tested are cultured and grown on a pair of suspension intervals of a certain sensing unit. All sensing units synchronously monitor the myocardial tissue 4 cultured in their respective units. When the myocardial tissue 4 generates micro-contraction force, it pulls on the suspension interval, causing the fiber optic grating 3 to deform and thus shifting the center wavelength of the fiber optic grating 3. The demodulator and the host computer calculate based on the center wavelength shift of each fiber optic grating 3, thereby synchronously and in real-time monitoring the contraction of each myocardial tissue 4.

[0061] Furthermore, the specific calculation process of the demodulator and the host computer is as follows:

[0062] The suspension section with fiber grating 3 is defined as the measurement suspension section, and the contact point between myocardial tissue 4 and the measurement suspension section is defined as the measured force point. In the initial state, the distance from the measured force point to the end of the measurement suspension section on the side with fiber grating 3 is L1, the distance from the measured force point to the end of the measurement suspension section on the side without fiber grating 3 is L2, the radius of the first grating region 301 is R1, and the radius of the second grating region 302 is R2.

[0063] When the myocardial tissue 4 generates a micro-contraction force F, the axial force generated in the suspension interval is F. t Therefore, the deformations ΔL1 and ΔL2 of the suspension section, divided into two parts by the force-bearing point, are respectively:

[0064]

[0065] Where a is the length of fiber grating 3, E is the elastic modulus of fiber 1, and A1 and A2 are the cross-sectional areas of the first grating region 301 and the second grating region 302, respectively.

[0066] See Figure 4 The force analysis of the direction perpendicular to the axis of the suspended section in the initial state yielded the following results.

[0067] Fcosθ=(F0+F t (sinα+sinβ)

[0068] Since θ is close to 0, we can assume that the direction of F is perpendicular to the axis of the suspension interval in the initial state. Therefore, we have:

[0069]

[0070] Therefore,

[0071]

[0072] For any point F in the above equation t0 Performing a Taylor series expansion at the given point, and ignoring expansion terms of order two and above (due to the small applied transverse force), the above equation transforms into:

[0073] F = F(F) t0 +F'(F t0 (F) t -F t0 )

[0074] in,

[0075]

[0076] Therefore,

[0077] F = F(F) t0 )+F'(F t0 (F) t -F t0 )=F'(F t0 )F t +(F(F t0 )-F t0 F'(F t0 ))=K1F t +K2

[0078] In the above formula, K1 and K2 are constant coefficients determined by the structural configuration parameters of the fiber Bragg grating sensor;

[0079] The center wavelength shift Δλ' of the first gate region 301 and the second gate region 302 B1 ,Δλ' B2 Represented as,

[0080]

[0081]

[0082] In the above formula, ρ e Let λ be the elastic-optical coefficient of fiber 1. B1 , λ B2 These are the initial center wavelengths of the first gate region 301 and the second gate region 302, respectively.

[0083] The relationship between the center wavelength drift of fiber optic grating 3 and the force and temperature it experiences is as follows:

[0084]

[0085] Where ζ is the thermo-optic coefficient of the optical fiber, σ is the linear thermal expansion coefficient of the optical fiber, and ΔT is the temperature change.

[0086] This embodiment also provides a method for fabricating the fiber Bragg grating sensor for high-throughput myocardial tissue μN-level contractile force as described above:

[0087] First, the radius of the suspension section with fiber grating 3 and the first grating region 301 of fiber grating 3 is etched to R1 by chemical etching to reduce the diameter, and then the radius of the second grating region 302 of fiber grating 3 is etched to R2.

[0088] Then, the optical fiber 1 is wound and bonded to the base 2, and all the suspension sections with fiber Bragg gratings 3 are located on the same side of the base 2. During the fixing process, a small preload is applied to the suspension sections with fiber Bragg gratings 3, and a larger preload is applied to the suspension sections without fiber Bragg gratings 3, so as to improve the sensitivity of the fiber Bragg grating sensor.

[0089] Specifically, the aforementioned chemical corrosion diameter reduction method is as follows:

[0090] The optical fiber 1 used consists of a removable coating, cladding, and core. First, the coating of the area to be etched is removed, and then the area to be etched is immersed in a hydrofluoric acid solution of a certain concentration. The area of ​​the optical fiber that does not need to be etched is kept away from the hydrofluoric acid solution. After a certain period of time, the radius of the part of the optical fiber immersed in the hydrofluoric acid solution is etched to R1.

[0091] The etched optical fiber 1 was then rinsed in clean water and then placed in a fume hood to dry.

[0092] Then, a certain concentration of hydrofluoric acid solution is dropped onto the second grating region 302 of the fiber grating and etched for a period of time until the radius of the etched area is etched to R2. Finally, the etched area is subjected to the above-mentioned rinsing and drying steps.

[0093] After the aforementioned chemical etching and diameter reduction process, the fiber grating 3 forms a first grating region 301 and a second grating region 302 with different radii. Because the force sensitivity of the first grating region 301 and the second grating region 302 differs, when the suspension section containing the fiber grating 3 is subjected to a lateral force, the original reflection peak of the fiber grating 3 splits into two independent reflection peaks, each corresponding to a different center wavelength. Furthermore, under dynamic force, the drift amounts of the two center wavelengths are also different. By utilizing the different force sensitivities of the two grating regions with different diameters within a single fiber grating 3, the influence of ambient temperature on the measurement results is eliminated through matrix decoupling.

[0094] The above description is merely an embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent structural or procedural transformations made based on the content of the present invention specification and drawings, or direct or indirect applications in other related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. A fiber Bragg grating sensor for high-throughput myocardial tissue μN-level contractile force, characterized in that: It includes several sensing units connected in series via optical fibers, with one end of the optical fiber connected to an external demodulator. Each sensing unit is used to measure the contractile force generated by in vitro cultured myocardial tissue. Each sensing unit includes a base and an optical fiber segment; The base is a hollow structure. The two ends of the optical fiber segment are fixed to one side of the base, and the middle part of the optical fiber segment is fixed to the other side of the base, so that the part of the optical fiber segment passing through the hollow area of ​​the base forms a pair of parallel suspension intervals. A fiber grating is set on one side of the suspension interval of the optical fiber segment. The radius of the suspension interval with the fiber grating in the optical fiber segment is smaller than the radius of the rest of the optical fiber segment. The fiber grating has a first grating area and a second grating area, and the radii of the first grating area and the second grating area are different. When the sensing unit measures the contractile force, the two ends of the myocardial tissue are cultured and grown on a pair of suspension intervals of a certain sensing unit. All sensing units synchronously monitor the myocardial tissue cultured in their respective units. When the myocardial tissue generates a micro-contraction force, it pulls the suspension interval, causing the fiber grating to deform and thus shifting the center wavelength of the fiber grating.

2. The fiber optic grating sensor for high-throughput myocardial tissue μN-level contractile force according to claim 1, characterized in that: Different sensing units are arranged horizontally adjacent to each other, perpendicular to the suspension section of the optical fiber segment; the optical fiber is reciprocated on the base of each sensing unit to form each optical fiber segment.

3. The fiber optic grating sensor for high-throughput myocardial tissue μN-level contractile force according to claim 2, characterized in that: Positioning bosses are provided on both sides of the base, and the optical fiber is fixed to the base by being wound and bonded to the side of the positioning bosses.

4. The fiber optic grating sensor for high-throughput myocardial tissue μN-level contractile force according to claim 3, characterized in that: The positioning boss includes a square boss and a semi-circular boss. The square boss is disposed on the base of the sensing unit at the beginning and end of the sensing unit and is used to fix the beginning and end of the optical fiber passing through the sensing unit. The semi-circular boss is used to fix the turning area of ​​the optical fiber.

5. The fiber optic grating sensor for high-throughput myocardial tissue μN-level contractile force according to claim 1, characterized in that: The first and second gate regions have the same length.

6. The fiber optic grating sensor for high-throughput myocardial tissue μN-level contractile force according to claim 1, characterized in that: The base is made of quartz glass.

7. The fiber optic grating sensor for high-throughput myocardial tissue μN-level contractile force according to claim 2, characterized in that: The minimum bending radius of the optical fiber is greater than 4 mm.

8. A high-throughput monitoring system for μN-level contractility of myocardial tissue, characterized in that: The invention includes a fiber Bragg grating sensor, a demodulator, and a host computer for high-throughput myocardial tissue μN-level contractile force as described in any one of claims 1-7, wherein the fiber segment of the fiber Bragg grating sensor is connected to the demodulator, and the demodulator is electrically connected to the host computer.

9. A method for monitoring high-throughput myocardial tissue μN-level contractility using the high-throughput myocardial tissue μN-level contractility monitoring system of claim 8, characterized in that: The two ends of the myocardial tissue to be tested are cultured and grown on a pair of suspension sections of a certain sensing unit. All sensing units synchronously monitor the myocardial tissue cultured in their respective units. When the myocardial tissue generates a micro-contraction force, it pulls on the suspension section, causing the fiber grating to deform and thus shifting the center wavelength of the fiber grating. The demodulator and the host computer calculate based on the center wavelength shift of each fiber grating, thereby synchronously and in real time monitoring the contraction of each myocardial tissue.

10. The method for monitoring high-throughput myocardial tissue μN-level contractility according to claim 9, characterized in that: The specific calculation process of the demodulator and the host computer is as follows. The suspension section equipped with a fiber Bragg grating is defined as the measurement suspension section, and the contact point between the myocardial tissue and the measurement suspension section is defined as the measured force point. Initially, the distance from the measured force point to the end of the measurement suspension section on the side with the fiber Bragg grating is... The distance from the measured force point to the end of the measurement suspension section on the side without a fiber optic grating is The radius of the first gate region is The radius of the second gate region is ; When the myocardial tissue generates a micro-contraction force F, the axial force generated in the suspension interval is: Therefore, the deformation of the suspension section is measured in two parts divided by the force point being measured. , They are respectively, in, The length of the fiber grating. The elastic modulus of the optical fiber. , These are the cross-sectional areas of the first and second gate regions, respectively. The force analysis of the direction perpendicular to the axis of the suspension section in the initial state yielded the following results. because Since F is close to 0, we assume that the direction of F is perpendicular to the axis of the suspension interval in the initial state. Therefore, we have: Therefore, At any point in the above equation Performing a Taylor series expansion at the given point, and ignoring expansion terms of order two or higher, the above equation transforms into: in, Therefore, In the above formula, , Constant coefficients determined by the structural configuration parameters of fiber Bragg grating sensor; Center wavelength shift of the first and second gate regions , Represented as, In the above formula, denoted as the optical elasticity coefficient of the optical fiber. , These are the initial center wavelengths of the first and second grating regions, respectively; The relationship between the center wavelength drift of a fiber Bragg grating and the forces and temperatures it experiences is as follows: in, This refers to the thermo-optic coefficient of the optical fiber. is the linear thermal expansion coefficient of optical fiber. This represents the change in temperature.

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