CN107314960B - Blood cell concentration sensor, preparation method thereof and testing device - Google Patents

Blood cell concentration sensor, preparation method thereof and testing device Download PDF

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CN107314960B
CN107314960B CN201710695544.8A CN201710695544A CN107314960B CN 107314960 B CN107314960 B CN 107314960B CN 201710695544 A CN201710695544 A CN 201710695544A CN 107314960 B CN107314960 B CN 107314960B
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optical fiber
femtosecond laser
corroded
mode
cavity
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CN107314960A (en
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廖常锐
王义平
李正勇
王英
何俊
朱峰
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Shenzhen University
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/06Investigating concentration of particle suspensions
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/01Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/06Investigating concentration of particle suspensions
    • G01N15/075Investigating concentration of particle suspensions by optical means

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Abstract

The invention is suitable for the optical fiber technology, and provides a preparation method of a blood cell concentration sensor, which comprises the following steps: placing the single-mode optical fiber with the coating layer removed on an optical fiber clamp and adjusting to enable the single-mode optical fiber to be positioned at a horizontal position; focusing the femtosecond laser on the fiber core plane of a single-mode fiber, adjusting energy, and controlling the femtosecond laser to perform line-by-line scanning processing on the single-mode fiber according to a preset Mach-Zehnder cavity model to obtain a fiber sample; and (3) placing the optical fiber sample in etching liquid for corrosion to prepare a Mach-Zehnder cavity, cleaning the corroded optical fiber sample, placing the optical fiber sample under a microscope for observing the quality of the corroded Mach-Zehnder cavity, testing a transmission spectrum, judging whether the quality and the transmission spectrum of the corroded Mach-Zehnder cavity reach preset standard values, if not, optimizing parameters, and if so, taking the corroded optical fiber sample as a blood cell concentration sensor. The sensor provided by the invention has the advantages of simple structure, simple manufacturing process, high reliability and high sensitivity.

Description

Blood cell concentration sensor, preparation method thereof and testing device
Technical Field
The invention belongs to the technical field of optical fibers, and particularly relates to a blood cell concentration sensor, a preparation method thereof and a testing device.
Background
Blood cell detection can reflect the health and disease phenomena of human body to a certain extent and quantity. The number and concentration of blood cells in healthy adults are fixed within a certain range, and if more or less than normal, a certain condition will be correspondingly manifested.
Space vehicles such as China airship have huge volumes, but have limited internal space, and large cell counting instruments such as blood cell analyzers and flow cytometry cannot be brought into space due to the characteristics of huge volumes, strong professional operability and the like. The outer space environment is bad, and the common electronic equipment cannot work normally due to strong electromagnetic and strong radiation, but how to detect blood cells of an astronaut under the bad environment so as to monitor the physical health condition of the astronaut is an important problem related to the life safety of the astronaut.
The existing equipment for detecting blood cells is huge in size, is too complex in detection process and low in efficiency, and has certain pollution.
Disclosure of Invention
The invention aims to solve the technical problems that the equipment for detecting blood cells provided by the prior art is huge in volume, the detection process is too complex and the efficiency is low.
The invention is realized in that a preparation method of the blood cell concentration sensor comprises the following steps:
placing the single-mode optical fiber with the coating layer removed on an optical fiber clamp, and adjusting the optical fiber clamp to enable the single-mode optical fiber to be positioned at a horizontal position;
focusing the femtosecond laser on the fiber core plane of the single-mode fiber, adjusting the energy of the femtosecond laser, and controlling the energy-adjusted femtosecond laser to perform line-by-line scanning processing on the single-mode fiber according to a preset Mach-Zehnder cavity model to obtain a fiber sample;
placing the optical fiber sample in a preset etching solution for etching to obtain a Mach-Zehnder cavity;
cleaning a corroded optical fiber sample, placing the corroded optical fiber sample under a microscope to observe the quality of the corroded Mach-Zehnder cavity, connecting the corroded optical fiber sample between a light source and a spectrometer, and testing the transmission spectrum of the corroded optical fiber sample;
judging whether the quality of the corroded Mach-Zehnder cavity or the transmission spectrum of the corroded optical fiber sample reaches a preset standard value, if not, adjusting the processing parameters or etching parameters of the femtosecond laser, taking a new single-mode fiber, and performing the step of placing the single-mode fiber with the coating layer stripped on an optical fiber clamp, wherein the adjustment of the processing parameters of the femtosecond laser comprises adjustment of the energy of the femtosecond laser, and the adjustment of the etching parameters comprises adjustment of the concentration and the corrosion time of the etching solution;
if so, the corroded optical fiber sample is used as a blood cell concentration sensor.
Further, the placing the single-mode fiber with the coating layer stripped on the fiber clamp, and adjusting the fiber clamp to enable the single-mode fiber to be located in the horizontal position includes:
fixing the single-mode optical fiber from which the coating is stripped on a two-dimensional adjustable pitching table, wherein the pitching table is positioned on a three-dimensional moving platform;
and controlling the movement of the three-dimensional moving platform, and adjusting the pitching platform to enable the optical fiber axial direction of the single-mode optical fiber to be parallel to the light spot moving direction of the femtosecond laser.
Further, the adjusting the energy of the femtosecond laser includes:
and adjusting the energy of the femtosecond laser through an attenuator consisting of a half wave plate and a grazing prism, and controlling the energy of the femtosecond laser to be 65nJ to 100nJ so as to form proper refractive index intensity modulation with local uniformity.
Further, after adjusting the energy of the femto-second laser, the method further includes:
the femtosecond laser is focused by a 100-fold immersion objective at the interface of the cladding and the core of the core plane of the single-mode fiber and enters the core at about 3 μm to 5 μm.
Further, the step of disposing the etching liquid includes:
adding deionized water and alcohol into hydrofluoric acid stock solution with the mass fraction of 40%, diluting the solution with the deionized water and the alcohol as buffer solution, and preparing hydrofluoric acid solution with the solution concentration of 5% -8%.
Further, placing the optical fiber sample in a preset hydrofluoric acid solution for corrosion comprises:
and placing the optical fiber sample in the oxyhydrogen solution, setting the corrosion temperature to be 40-45 ℃, adopting a water bath heating mode to perform corrosion, and adding magnetic stirring to perform disturbance.
Further, the etching time is controlled to be 10 to 20 minutes.
The invention also provides a blood cell concentration sensor, which is prepared by the preparation method.
The invention also provides a blood cell concentration testing device which is prepared from polydimethylsiloxane and comprises a micro-channel, a liquid inlet channel and a liquid outlet channel, wherein the liquid inlet channel and the liquid outlet channel are communicated with the micro-channel.
Further, the diameter of the micro-channel is 300 μm to 359 μm.
Compared with the prior art, the invention has the beneficial effects that: the blood cell concentration sensor based on the single-mode fiber, which is manufactured by adopting the preparation method provided by the embodiment of the invention, adopts an all-fiber structure, so that the influence of electromagnetic interference on a detection result can be avoided. Meanwhile, the sensor is simple in structure and manufacturing process and high in reliability, when the sensor is used, the blood cell solution is injected into a Mach-Zehnder cavity of a single-mode fiber from a liquid inlet channel of a testing device by using an injector, two ends of the single-mode fiber are connected with a light source and a spectrometer, and the change of the blood cell concentration is detected in a mode of detecting the drift condition of an interference spectrum, so that the sensor has the characteristic of high sensitivity.
Drawings
FIG. 1 is a schematic diagram of a blood cell concentration sensor according to an embodiment of the present invention;
FIG. 2 is a flowchart of a method for manufacturing a blood cell concentration sensor according to an embodiment of the present invention;
FIG. 3 is a schematic diagram of a system for preparing a blood cell concentration sensor according to an embodiment of the present invention;
FIG. 4 is a schematic diagram of a scanning trace of a femtosecond laser provided by an embodiment of the invention;
FIG. 5 is a model real-time diagram of a Mach-Zehnder cavity fabricated by femtosecond laser processing provided by an embodiment of the invention;
FIG. 6 is a physical diagram of a Mach-Zehnder cavity after being corroded by hydrofluoric acid solution, which is provided by the embodiment of the invention;
FIG. 7 is an interference spectrum of a single mode fiber with a Mach-Zehnder cavity in air provided by an embodiment of the present invention;
fig. 8 is a schematic structural diagram of a blood cell concentration test apparatus according to an embodiment of the present invention.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The embodiment of the invention provides a blood cell concentration sensor prepared by a femtosecond laser wet etching technology and a manufacturing method thereof, wherein a Mach-Zehnder MZ cavity is manufactured in a single-mode fiber, and the detection of the blood cell concentration is realized by detecting the change of the refractive index of a blood cell solution in the MZ cavity.
Fig. 1 shows a blood cell concentration sensor provided by an embodiment of the present invention, which is a single-mode fiber having a mach-zehnder cavity. Light is transmitted in the core of the single mode fiber 101, is split into two beams through the MZ cavity 102, one beam is still transmitted along the core, the other beam is transmitted through the MZ cavity 102, and the last two beams are recombined in the core of the single mode fiber 101. Since the refractive indexes of media through which the two beams pass are different, an optical path difference is generated, thereby forming MZ interference. Ambient liquid enters the MZ cavity 102 through the microfluidic channel 103 changing the refractive index of the cavity medium, such that this change is detected in the transmission spectrum.
Fig. 2 shows a method for preparing a blood cell concentration sensor according to an embodiment of the present invention, including:
s201, placing the single-mode optical fiber with the coating layer removed on an optical fiber clamp, and adjusting the optical fiber clamp to enable the single-mode optical fiber to be positioned at a horizontal position;
s202, focusing the femtosecond laser on the fiber core plane of the single-mode fiber, adjusting the energy of the femtosecond laser, and controlling the energy-adjusted femtosecond laser to perform line-by-line scanning processing on the single-mode fiber according to a preset Mach-Zehnder cavity model to obtain a fiber sample;
s203, placing the optical fiber sample in a preset etching solution for etching to etch a Mach-Zehnder cavity;
s204, cleaning the corroded optical fiber sample, placing the corroded optical fiber sample under a microscope to observe the quality of the corroded Mach-Zehnder cavity, connecting the corroded optical fiber sample between a light source and a spectrometer, and testing the transmission spectrum of the corroded optical fiber sample;
s205, judging whether the quality of the corroded Mach-Zehnder cavity or the transmission spectrum of the corroded optical fiber sample reaches a preset standard value, if not, adjusting the processing parameters or etching parameters of the femtosecond laser, taking a new single mode fiber, and performing the step of placing the single mode fiber with the coating layer stripped on an optical fiber clamp, wherein the adjustment of the processing parameters of the femtosecond laser comprises adjustment of the energy of the femtosecond laser, and the adjustment of the etching parameters comprises adjustment of the concentration and the corrosion time of the etching liquid. In the step, if the quality of the Mach-Zehnder cavity or the transmission spectrum of the optical fiber sample obtained by corrosion is judged to not reach a preset standard value, the processed single-mode optical fiber is not in accordance with the requirement, the processing parameters of femtosecond laser or the etching parameters are required to be adjusted, a new single-mode optical fiber is taken, the processing is carried out again, and the single-mode optical fiber which is failed to be processed originally is discarded.
And S206, taking the corroded optical fiber sample as a blood cell concentration sensor if the sample reaches the standard.
The following specifically describes a method for manufacturing a blood cell concentration sensor according to an embodiment of the present invention:
step 1, placing a single-mode fiber with a stripped coating layer on an optical fiber clamp, and adjusting the optical fiber clamp to enable the single-mode fiber to be positioned at a horizontal position;
as shown in fig. 3, the single-mode optical fiber from which the coating layer is peeled off is fixed on a two-dimensional adjustable pitching table, which is located on a three-dimensional moving platform. The fiber core axial direction of the single-mode fiber is parallel to the spot moving direction of the femtosecond laser by adjusting the two-dimensional adjustable pitching platform and the three-dimensional moving platform. The attenuator consisting of the half wave plate and the Greenwich prism is adjusted, and the energy of the femtosecond laser is controlled to be 65-100nJ, so that the femtosecond laser can form local more uniform proper refractive index intensity modulation. The three-dimensional moving platform is controlled by a computer to move, so that the femtosecond laser is focused at the junction of the fiber core and the cladding of the fiber core plane of the single-mode fiber, and then the Y-axis is moved to enable the focal spot of the femtosecond laser to enter the fiber core of the single-mode fiber by about 3-5 mu m.
And 2, controlling the femtosecond laser after energy adjustment to scan and process the single-mode fiber to obtain a fiber sample.
The track of the femtosecond laser scanning is shown in fig. 4, and in specific operation, the femtosecond laser is stationary, the three-dimensional moving platform is moved, and the movement of the femtosecond laser is described below by taking the three-dimensional moving platform as a stationary reference. The three-dimensional moving platform with high precision is arranged to have the moving speed of 5-10 mu m/s on the X, Y, Z axis. The shutter is opened, the three-dimensional moving platform is controlled to move towards the X-axis direction, the femtosecond laser starts scanning, the femtosecond laser stops after scanning along the positive direction (or the reverse direction) of the X-axis by about 60-100 mu m, continues to move along the negative direction (positive direction) of the Z-axis by about 2-3 mu m, then stops along the negative direction (positive direction) of the X-axis by about 60-100 mu m, moves along the negative direction (direction vertical to the fiber core and away from the fiber core) by about 1-1.5 mu m, then stops along the positive direction (or the reverse direction) of the X-axis by about 60-100 mu m, then stops along the positive direction (positive direction) of the X-axis by about 60-100 mu m, and moves along the negative direction of the Y-axis by about 1-1.5 mu m. And finally, processing a plurality of micro channels along the Y direction to connect the MZ cavity and the surface of the optical fiber cladding, and finally obtaining the optical fiber sample with the MZ cavity. Fig. 5 shows the MZ cavity after femtosecond laser micromachining. As can be seen from fig. 5, the processed areas are darker in color, as the processed distinguishing material is modified by the refractive index, which is greater than the unprocessed areas, and thus darker in color when viewed under a microscope.
And 3, preparing a hydrofluoric acid solution for corrosion.
Mixing 40% hydrofluoric acid solution with alcohol and deionized water according to volume ratio, and preparing 5% -8% hydrofluoric acid solution. The purpose of the addition of alcohol is to buffer. The material of the container contacted with hydrofluoric acid is polytetrafluoroethylene. The fiber sample was cut 2-3mm from the MZ cavity structure and then inserted vertically into a container containing the configured hydrofluoric acid solution. Adding water into a magnetic stirrer, setting the temperature to be 40-45 ℃, placing a container with hydrofluoric acid solution left in the container after the temperature is stable, setting the corrosion time to be 10-20 minutes, sequentially cleaning with ethanol and deionized water, placing the container into an oven for drying, and welding the corroded optical fiber sample with a single-mode optical fiber.
And 4, placing the corroded optical fiber sample under a microscope to observe the quality of the corroded MZ cavity.
The situations that may occur in actual operation are: incomplete corrosion, irregular cavity shape, excessive corrosion, complete core corrosion, etc. If the above situation occurs, the processing parameters of the femtosecond laser need to be modified in the step 2, the processing parameters include laser energy, scanning speed and the like, or the concentration and etching time of the hydrofluoric acid solution need to be modified in the step 3 until the structure shown in fig. 5 is etched. From fig. 6 it can be seen that the etched area material is completely removed and the MZ cavity is in communication with the outside through the micro-channels, with some of the core remaining. And respectively connecting the two ends of the corroded optical fiber sample with a light source and a spectrometer, and detecting an interference spectrogram of the MZ cavity. If the interference spectrum is not detected or the spectrum contrast is lower than 5dB, the corresponding parameters are modified by returning to the step 2 or the step 3, and the experiment is repeated. Fig. 7 shows an interference spectrum with a cavity length of 98 μm, the interference contrast reaching 17dB.
And 5, manufacturing a blood cell concentration testing device.
The basic components of PDMS (polydimethylsiloxane) glue and a curing agent are completely mixed according to the weight ratio of 10:1, and then the mixture is placed in a vacuumizing instrument to suck out bubbles in the glue. Placing iron wires with the diameter of 300-350 mu m into a model, pouring the vacuumized glue into the model, placing the whole into a temperature box for baking, setting the temperature to be 80-90 ℃ and the time to be 1-1.5 hours. And after baking, completely curing the PDMS glue, and drawing out the iron wires to form the micro-channels. Two holes are punched above the micro-channel by using a puncher, and then a metal conduit is inserted to form a liquid inlet channel and a liquid outlet channel. The finished test device is shown in fig. 8.
And 6, placing the corroded optical fiber sample in a micro-channel of a testing device, and testing the concentration of blood cells.
As shown in fig. 8, the etched fiber sample is placed in a microchannel 807 of a test apparatus 800, and both ends of the microchannel 807 are sealed with an ultraviolet curable adhesive. One end of the optical fiber sample is connected with a super-continuous light source 802, the other end is connected with a spectrometer 806, the injector 801 is connected with a liquid inlet channel 803 of the testing device through a plastic hose, and a liquid outlet channel 804 is connected with a waste liquid collecting device 805. The syringe 801 is used to draw the blood cell solution, the injection rate is set, the blood cell solution enters the MZ cavity of the optical fiber sample through the liquid inlet channel 803 and the micro channel 807, and the data is recorded after the spectrum is stable. Then the ethanol is replaced to be injected into the testing device for structural cleaning, then another concentration of blood cell solution is replaced to be injected, and the spectrograms of blood cells with different concentrations are tested in sequence. The densities of blood cells at different concentrations are different to show a difference in refractive index. When blood cell solutions with different concentrations are injected into the MZ cavity, the refractive index of the medium in the MZ cavity is changed, so that the refractive index difference between the two interference arms is changed, and the reflection is that the interference spectrum has wavelength drift in the spectrum. The blood cell concentration sensor with the MZ cavity provided by the embodiment of the invention has high refractive index sensitivity and low refractive index detection limit, and can detect 10 -5 Shows excellent sensing characteristics in detecting blood cell concentration.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the invention.

Claims (9)

1. A method for manufacturing a blood cell concentration sensor, comprising:
fixing the single-mode optical fiber from which the coating is stripped on a two-dimensional adjustable pitching table, wherein the pitching table is positioned on a three-dimensional moving platform;
controlling the movement of the three-dimensional moving platform, and adjusting the pitching platform to enable the optical fiber axial direction of the single-mode optical fiber to be parallel to the light spot movement direction of the femtosecond laser;
focusing the femtosecond laser on the fiber core plane of the single-mode fiber, adjusting the energy of the femtosecond laser, and controlling the energy-adjusted femtosecond laser to perform line-by-line scanning processing on the single-mode fiber according to a preset Mach-Zehnder cavity model to obtain a fiber sample;
placing the optical fiber sample in a preset etching solution for etching to obtain a Mach-Zehnder cavity;
cleaning a corroded optical fiber sample, placing the corroded optical fiber sample under a microscope to observe the quality of the corroded Mach-Zehnder cavity, connecting the corroded optical fiber sample between a light source and a spectrometer, and testing the transmission spectrum of the corroded optical fiber sample;
judging whether the quality of the corroded Mach-Zehnder cavity or the transmission spectrum of the corroded optical fiber sample reaches a preset standard value, if not, adjusting the processing parameters or etching parameters of the femtosecond laser, taking a new single-mode fiber, and performing the step of placing the single-mode fiber with the coating layer stripped on an optical fiber clamp, wherein the adjustment of the processing parameters of the femtosecond laser comprises adjustment of the energy of the femtosecond laser, and the adjustment of the etching parameters comprises adjustment of the concentration and the corrosion time of the etching solution;
if so, the corroded optical fiber sample is used as a blood cell concentration sensor.
2. The method of manufacturing according to claim 1, wherein the adjusting the energy of the femtosecond laser includes:
and adjusting the energy of the femtosecond laser through an attenuator consisting of a half wave plate and a grazing prism, and controlling the energy of the femtosecond laser to be 65nJ to 100nJ so as to form proper refractive index intensity modulation with local uniformity.
3. The method of manufacturing according to claim 1, wherein after the adjusting the energy of the femtosecond laser, further comprising:
the femtosecond laser is focused by a 100-fold immersion objective at the interface of the cladding and the core of the core plane of the single-mode fiber and enters the core at about 3 μm to 5 μm.
4. The method of preparing as claimed in claim 1, wherein the step of disposing the etching liquid comprises:
adding deionized water and alcohol into hydrofluoric acid stock solution with the mass fraction of 40%, diluting the solution with the deionized water and the alcohol as buffer solution, and preparing hydrofluoric acid solution with the solution concentration of 5% -8%.
5. The method of preparing as claimed in claim 4, wherein etching the optical fiber sample in a predetermined hydrofluoric acid solution comprises:
and placing the optical fiber sample in the hydrofluoric acid solution, setting the corrosion temperature to be 40-45 ℃, adopting a water bath heating mode to perform corrosion, and adding magnetic stirring to perform disturbance.
6. The method of claim 1, wherein the etching time is controlled to be 10 to 20 minutes.
7. A blood cell concentration sensor, characterized in that it is produced by the production method according to any one of claims 1 to 6.
8. A blood cell concentration testing device, wherein the testing device is prepared from polydimethylsiloxane, and comprises a micro-channel, a liquid inlet channel and a liquid outlet channel, wherein the liquid inlet channel and the liquid outlet channel are communicated with the micro-channel, and the blood cell concentration sensor as claimed in claim 7 is arranged in the micro-channel.
9. The test device of claim 8, wherein the micro-channel has a diameter of 300 μm to 359 μm.
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