CN119086367A - A gaseous microembolus detection system - Google Patents

Abstract

The invention belongs to the technical field of biomedicine, in particular to a gaseous micro-embolic detection system, which comprises a laser, a whispering gallery mode microcavity sensing device, a photoelectric detector, a PDH laser frequency stabilizer and an oscilloscope, combines the high sensitivity of the whispering gallery mode microcavity sensor with the rapid response of the PDH frequency stabilization technology, the method can capture the complex optical signal change caused by the bubble flowing in real time, accurately identify the micron-sized bubbles at microsecond speed, and the ultrasensitive detection of the micron-sized bubbles has wide application prospect in biomedicine, especially in diagnosis and treatment of gaseous micro-emboli and cerebral micro-emboli.

Description

Gaseous micro-embolus detection system

Technical Field

The application relates to the technical field of biomedicine, in particular to a gaseous micro-embolic detection system.

Background

In recent years, with the rapid development of medical devices and cardiac surgical techniques, the extracorporeal Circulation (CPB) technique has been widely used in heart and coronary artery surgery, greatly improving the survival rate of surgical patients. However, during heart surgery, a low pressure region is created around the valve during mechanical heart valve closure, resulting in the formation of microbubble emboli (GME). A great deal of clinical evidence suggests that up to 80% of patients develop symptoms of psychotic disorders such as delirium, cognitive dysfunction, affective disorders, etc. shortly after CPB surgery, with a quarter of patients still persisting for 6 months. Studies have shown that one of the important causes of mental disorders in CPB post-operative patients is the gaseous micro-embolic (GME), which, through blood circulation, enters the capillaries of the brain, triggering diffuse cerebral ischemia, leading to post-operative nerve damage. The GME introduced during surgery undoubtedly adds to the pain and economic burden of the patient, as mental disorders and injuries to the nervous system are difficult to cure and the treatment costs are expensive.

In order to strictly prevent GME from entering human blood circulation, currently, common methods for detecting bubbles in a liquid path include an ultrasonic detection method, a capacitive detection method and a pressure sensor method. The ultrasonic detection method is the most widely used air plug detection method at present, and utilizes the principle that gaseous micro-emboli in blood and red blood cells have different acoustic impedances to enable ultrasonic beams to be reflected and scattered at the interface between the emboli and the blood at the same time, so that transient high-intensity signals are detected to judge the passing of bubbles. However, ultrasonic detection is costly, equipment is bulky, and sensitivity decreases with time, and is very prone to missed diagnosis for micron-sized bubbles. The capacitive detection method captures the change of the electric signal through the medium change between the two polar plates, can quantitatively detect the passing air bubbles, but increases the operation and maintenance difficulty of technicians with high calibration accuracy. The pressure sensor can sensitively capture the pressure change of the bubble passing through, but is limited by the liquid flow rate and the non-pressure pipeline, and cannot be widely applied to various fields. In order to solve the above problems, there is a need to develop a bubble detection system that has high sensitivity, high portability, and simple operation, and detects micro-scale bubbles in a liquid path in real time.

Disclosure of Invention

The application provides a new method for detecting gaseous micro-emboli generated in the extracorporeal circulation process, has high sensitivity, high stability and portability, and can detect the size and the number of the gaseous micro-emboli in real time by observing the mode change of the optical micro-bubble cavity.

The detection system comprises a laser, an echo wall mode microcavity sensing device, a photoelectric detector, a PDH laser frequency stabilizer and an oscilloscope;

further, the laser is a semiconductor laser, and can be used for emitting laser by rapidly adjusting the frequency of laser driving current and eliminating the long-term frequency drift phenomenon of the laser by controlling the temperature of the laser;

The whispering gallery mode microcavity sensing device is formed by coupling whispering gallery mode optical microcavities and tapered optical fibers and is used for forming a resonance mode, the two ends of the whispering gallery mode optical microcavities are connected with Teflon tubes, one Teflon tube is connected with an injector, the other Teflon tube is put into solution, the injector is pulled to enable the solution to be full of a microbubble cavity and the Teflon tube, and then the Teflon tube put into the solution alternates back and forth in air and the solution, so that bubbles are generated, when micron-sized bubbles enter a sensing area, the surrounding environment in the microcavities is changed, the originally stable environment is damaged, the whispering gallery mode is changed, namely mode deviation, mode broadening, mode splitting, mode intensity change and the like are caused;

further, the photodetector is used for optical signal conversion and displays the signal on the oscilloscope so as to observe the mode;

Further, the PDH laser frequency stabilizer comprises a function generator, a photoelectric modulator, a mixer and a filter, wherein the laser frequency is locked to the resonance of the WGM resonant cavity in real time by accurately adjusting parameters and settings of the photoelectric modulator, the signal generator, the mixer and the proportional-integral circuit, and external disturbance can be amplified by combining feedback control of an error signal, so that the detection precision and stability are improved, and the real-time monitoring of the change of the WGM resonant mode frequency is realized.

Compared with the prior art, the invention has the beneficial effects that:

The detection system can lock the laser frequency to the resonance of the WGM resonant cavity in real time, and can amplify external disturbance by combining with feedback control of an error signal, so that the detection precision and stability are improved, the real-time monitoring of the change of the WGM resonant mode frequency is realized, no additional mode fitting is needed, and the purpose of real-time observation of microbubbles is realized.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the application and together with the description, serve to explain the principles of the application.

FIG. 1 is a schematic diagram of the structure of the present application;

FIG. 2 is a schematic diagram of the whispering gallery mode optical microcavity before and after deionized water is introduced;

FIG. 3 is a graph of voltage signal change as the flow rate of water in a whispering gallery mode optical microcavity increases;

FIG. 4 is a graph of voltage signal change as the flow rate of water in a whispering gallery mode optical microcavity slows;

FIG. 5 is a graph of pulse signal variation for six bubbles of approximately 1.2 μL in a whispering gallery mode optical microcavity filled with deionized water;

FIG. 6 is a graph of pulse signal variation through a bubble having a volume of about 2.5. Mu.L in a whispering gallery mode optical microcavity filled with serum;

FIG. 7 is a graph of pulse signal variation through a bubble having a volume of about 2.5. Mu.L in another set of serum-filled whispering gallery mode optical microcavities;

Fig. 8 is a graph of pulse signal variation through micron-sized bubbles in a whispering gallery mode optical microcavity filled with serum.

Detailed Description

For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

Specifically, an electric spark is generated by using an electrode of an optical fiber fusion splicer, the capillary is heated to reach the melting temperature, pressurization is carried out while the quartz capillary is heated in the fusion splicer, the capillary can expand, microbubbles with certain specification can be obtained, the optical fiber is tapered by using a tapering device, the tapered optical fiber with the taper area as thin as 2 mu m is obtained, and the tapered optical fiber and the manufactured microbubbles are coupled under an optical platform to obtain the whispering gallery mode microcavity sensing device.

On the basis of a whispering gallery mode type microcavity sensing device, a PDH-WGM microcavity sensing system is built, as shown in fig. 1, 780 nm single-frequency DFB laser is modulated by an electro-optical modulator and then is coupled into a microbubble WGM cavity by a tapering optical fiber, then transmitted light is divided into two paths by a 1X 2 coupler, the first path enters a photoelectric detector to be converted into an electric signal and then is input into an oscilloscope to monitor the coupling mode in real time, a second path of photoelectric signal is mixed with a channel 2 signal channel of a function generator to generate an error signal, the channel 2 signal frequency is kept consistent with the modulation frequency (channel 1) applied to an EOM, the error signal generated by the mixer is input into a high-speed ratio example integrating controller by a low-pass filter, and the controller generates a control signal to rapidly adjust the laser frequency so as to maintain the laser frequency on the resonance frequency of the WGM microbubble cavity in real time.

The system carries out the verification step of sensing the environmental change in real time:

In this embodiment, teflon tubes are connected to two ends of the whispering gallery mode optical microcavity, one teflon tube is connected to the syringe, the other teflon tube is placed in deionized water, the syringe is pulled to fill the microbubble cavity and the teflon tube with deionized water, as shown in fig. 2, it can be observed that the Q value of the mode is locked by PDH from 2.09×10 ⁶ before water is introduced to 1.90×10 ⁶ after water is introduced, when the flow rate of water increases, a voltage change graph as shown in fig. 3 is observed, the voltage value gradually decreases with the increase of the flow rate, and when the flow rate of water slows down, a voltage change graph as shown in fig. 4 is observed, and the voltage value gradually increases with the decrease of the flow rate.

The system carries out real-time sensing on bubbles:

The teflon tube ends placed in the water were removed, briefly exposed to air and quickly replaced, allowing a small amount of gas to enter the lumen. The operation is repeated, bubbles with different distribution sizes in the pipeline can be obtained, and quantitative analysis can be carried out on the bubbles by measuring the length of the bubbles occupying the lumen. 6 bubbles with similar sizes and similar intervals are sequentially introduced, the average volume of the bubbles is calculated to be about 1.25 mu L through measurement, and in a PDH-WGM microcavity sensing system, the change condition of signals when the bubbles pass through a microbubble cavity is observed, and as shown in figure 5, the whole pulse is slightly upward moving due to the slowing of the flow rate in the cavity. When the bubbles pass through the micro-bubble cavity, the mode is changed rapidly, the originally stable signal spectral line on the oscilloscope is changed into a high-level pulse wave, and the stable state is restored after the bubbles pass through. By testing that the pulse wave waveforms of bubbles with different sizes pass through the microbubble cavity are all rising and falling, the method has certain regularity. Through multiple experimental observations, a conclusion is obtained that when no strong external interference exists, the system which is filled with deionized water can always keep a locking state without losing the lock. During the period, when the system is instantaneously interfered by external high frequency, the system can quickly react and be locked again. It has been found that the flow of bubbles through the WGM cavity causes a change in the pressure at the surface of the microbubbles, thereby altering the resonant frequency of the WGM cavity.

The deionized water is replaced by serum, bubbles with the average volume of about 2.5 mu L are introduced by the same method, and a high Q value mode is locked, so that pulse signal graphs shown in fig. 6 and 7 are obtained. The conditions such as turbulence generated in the micro-bubble cavity, uneven distribution of biological macromolecules in the cavity wall, and larger flow velocity in the center of the viscous liquid tube than the flow velocity close to the tube wall, gravity, friction force, and the influence on the tube wall pressure and other acting forces can be considered. However, the irregularity of the pulse signal does not affect the sensitivity of the system for detecting the passage of bubbles, even if micro-sized bubbles which are difficult to be found by naked eyes pass, the high-Q mode can still generate obvious offset, and the pulse signal diagram is shown in fig. 8, namely the change of the pulse signal when the micro-sized bubbles pass.

Research shows that when the flow rate of solution passing through the micro-bubble cavity is changed, the corresponding voltage signal is changed, when bubbles pass through the micro-bubble cavity, the regular pulse signal is changed, and even if the micro-bubbles pass through, the mode is shifted, so that the pulse signal is generated.

The foregoing is merely illustrative of the present invention, and the present invention is not limited thereto, and any person skilled in the art will readily recognize that variations or substitutions are within the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Finally, the foregoing description of the preferred embodiment of the invention is provided for the purpose of illustration only, and is not intended to limit the invention to the particular form disclosed, but on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention.

Claims (6)

1. A gaseous microembolus detection system, comprising: A laser is used to emit laser; a whispering gallery mode microcavity sensor device is connected to the laser and is used to form a resonance mode; a photodetector is connected to the whispering gallery mode microcavity sensor device and is used to convert the optical signal transmitted from the whispering gallery mode microcavity sensor device into an electrical signal; an oscilloscope is connected to the photodetector and is used to display the change of the electrical signal in real time; a PDH laser frequency stabilizer is connected to the laser and the photodetector and is used to realize the real-time detection of biological molecules with a high signal-to-noise ratio. 2. A gaseous microemboli detection system according to claim 1, characterized in that the laser is a semiconductor laser, and laser scanning can be achieved by quickly adjusting the frequency of the laser driving current. 3. A gaseous microemboli detection system according to claim 1, characterized in that the whispering gallery mode microcavity sensing device is composed of a whispering gallery mode optical microcavity coupled with a tapered optical fiber. When gaseous microemboli enter the sensing area, they will cause changes in the surrounding environment in the microcavity, thereby destroying the originally stable environment and inducing changes in the whispering gallery resonance mode, namely, mode shift, mode broadening and mode splitting changes. 4. A gaseous microemboli detection system according to claim 1, characterized in that the photoelectric detector receives light signals and converts the light signals into electrical signals, and when the light field pattern changes, the output electrical signal also changes accordingly. 5. A gaseous microemboli detection system according to claim 1, characterized in that the oscilloscope receives the electrical signal converted by the photoelectric detector and presents the change of the signal in real time. 6 . The gaseous microemboli detection system according to claim 1 , wherein the PDH laser frequency stabilizer comprises: a function generator, an optoelectronic modulator, a mixer and a filter.