CN110137792B - Multi-core optical fiber cell laser with stretching function - Google Patents

Multi-core optical fiber cell laser with stretching function Download PDF

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CN110137792B
CN110137792B CN201910396363.4A CN201910396363A CN110137792B CN 110137792 B CN110137792 B CN 110137792B CN 201910396363 A CN201910396363 A CN 201910396363A CN 110137792 B CN110137792 B CN 110137792B
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CN110137792A (en
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苑婷婷
张晓彤
苑立波
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Guilin University of Electronic Technology
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    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B6/00—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings
    • G02B6/02—Optical fibres with cladding with or without a coating
    • G02B6/02042—Multicore optical fibres
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B6/00—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings
    • G02B6/24—Coupling light guides
    • G02B6/26—Optical coupling means
    • G02B6/262—Optical details of coupling light into, or out of, or between fibre ends, e.g. special fibre end shapes or associated optical elements
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B6/00—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings
    • G02B6/24—Coupling light guides
    • G02B6/26—Optical coupling means
    • G02B6/264—Optical coupling means with optical elements between opposed fibre ends which perform a function other than beam splitting
    • G02B6/266—Optical coupling means with optical elements between opposed fibre ends which perform a function other than beam splitting the optical element being an attenuator
    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21K—TECHNIQUES FOR HANDLING PARTICLES OR IONISING RADIATION NOT OTHERWISE PROVIDED FOR; IRRADIATION DEVICES; GAMMA RAY OR X-RAY MICROSCOPES
    • G21K1/00—Arrangements for handling particles or ionising radiation, e.g. focusing or moderating
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01S—DEVICES USING THE PROCESS OF LIGHT AMPLIFICATION BY STIMULATED EMISSION OF RADIATION [LASER] TO AMPLIFY OR GENERATE LIGHT; DEVICES USING STIMULATED EMISSION OF ELECTROMAGNETIC RADIATION IN WAVE RANGES OTHER THAN OPTICAL
    • H01S3/00—Lasers, i.e. devices using stimulated emission of electromagnetic radiation in the infrared, visible or ultraviolet wave range
    • H01S3/05—Construction or shape of optical resonators; Accommodation of active medium therein; Shape of active medium
    • H01S3/08—Construction or shape of optical resonators or components thereof
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01S—DEVICES USING THE PROCESS OF LIGHT AMPLIFICATION BY STIMULATED EMISSION OF RADIATION [LASER] TO AMPLIFY OR GENERATE LIGHT; DEVICES USING STIMULATED EMISSION OF ELECTROMAGNETIC RADIATION IN WAVE RANGES OTHER THAN OPTICAL
    • H01S3/00—Lasers, i.e. devices using stimulated emission of electromagnetic radiation in the infrared, visible or ultraviolet wave range
    • H01S3/09—Processes or apparatus for excitation, e.g. pumping
    • H01S3/091—Processes or apparatus for excitation, e.g. pumping using optical pumping

Abstract

The invention provides a multi-core optical fiber cell laser system with a stretching function. The optical fiber-cell laser mainly comprises the following four parts: (1) the end of the multi-core optical fiber with a novel structure is polished into a rotationally symmetrical double-angle cone frustum shape to prepare the optical fiber optical tweezers; (2) the micro optical resonant cavity is internally provided with a gain medium with an optical amplification function; (3) a light source capable of providing cell capture photodynamic and a gain medium excitation light source; (4) a cell output laser detection spectrometer. The output spectrum of the microsphere optical resonant cavity in the cell is very sensitive to the weak change of environmental physical parameters such as cytosol in the cell, and can be measured through an amplified laser signal output by the multi-core cone optical fiber. The invention can be used for single cell capture and cell laser spectrum measurement, and can be widely applied to the technical fields of single cell manipulation, sensing, measurement and analysis.

Description

Multi-core optical fiber cell laser with stretching function
(I) technical field
The invention relates to a multi-core optical fiber cell laser system with a stretching function, which can be used for cell capture, cell laser spectrum measurement and cell laser self-assembly, and is particularly suitable for the technical field of single cell manipulation, measurement and analysis.
(II) background of the invention
U.S. scientists t.h. meiman, et al, in 1960, successfully created the first ruby crystal laser in the world, he-ne, et al, in 1961, successfully developed he-ne lasers, and r.n. hall, et al, in 1962, developed gaas semiconductor lasers. The birth of the laser device indicates that people have the ability to regulate and control the emission direction, the phase, the frequency, the polarization and the like of a plurality of photons, so that the understanding and the application of the light reach a higher level. The laser shows more than imaginable application value in the miniaturization and cross discipline direction, so the field of optical flow laser is produced. The optical fluid is a novel research field with multidisciplinary intersection formed by combining the unique advantages of optics and fluids, the concept of the optical fluid is proposed by the university of California Ringschen in 2003, and biological organisms have very wide application prospects in the fields of biomedical diagnosis, sensing detection, imaging and the like due to the existence of natural liquid environment.
The cell laser is a special optical flow laser (advances in laser and optoelectronics, and research and application reviews of cell lasers, 2018,55:120001), and can realize laser output of cells under excitation of external energy in a liquid environment for living of organisms in vitro or directly in organisms. Compared with the fluorescence signal detection method commonly used in various fields of biomedicine at present, the laser signal detection method has unique advantages. Firstly, the laser signal is spontaneous radiation light of which stimulated radiation light is different from a fluorescence signal, and has good directivity after signal amplification and feedback of a resonant cavity; secondly, when the laser signal of the excitation source is higher than the threshold value, the signal energy output by the working particles is far higher than that of the fluorescent signal, so that the resolution and the sensitivity of the laser signal detection are also far higher than those of the fluorescent signal detection, and the spectral width of the laser signal output spectral line width is extremely narrow compared with that of the fluorescent spectrum of the luminescent material, thereby being beneficial to timely response in the sample detection process. The commonly used gain medium in cell lasers is typically a fluorescent material, such as fluorescent protein (nano phosphor, Single-cell biological lasers,2011,5: 406-.
In 6.2001, Gather et al, harvard university, made human embryonic kidney cells emit laser signals (natural PHOTONICS, Single-cell biological lasers,2011,5: 406-. In 2015, Humar et al, of medical institute of Harvard university, developed multiple cell lasers (NATURE PHOTONICS, Intracellular microloasters, 2015,9: 572-.
With respect to optically induced surface forces resulting in cell trapping and stretching, a common method of stretching cells is to deform a single suspended cell by optically induced surface forces via optical stretchers in combination with microfluidic delivery, and to propagate light through two oppositely directed spaces so that cells within a microfluidic channel can be trapped and deformed by a diverging laser beam (biophysis, The optical stretcher: a novel laser to micromanipulate cells,81: 767-. Other methods are also known, in which red blood cells are connected to two silica beads treated with a protein coating, one of the beads is fixed to a glass plate and the other bead is captured by an optical tweezer, and the beads move with the movement of the optical tweezer during the movement of the optical trap, thereby achieving the effect that the red blood cells are stretched (Acta Mater, Large deformation of living cells using laser tracks, 52, 1837; 1845, 2004). In addition, the Cell may be stretched by directly adhering a glass or metal tip to the Cell and measuring the viscosity of the Cell by stretching and bending the distance between the tips (Biophysical Journal, deep Function of a Single Living Cell,88: 2224-. The cell laser based on the novel optical fiber structure integrates the functions of cell capture, stretching, excitation, receiving and the like, greatly reduces the number and size of required instruments, reduces experiment steps and reduces experiment difficulty.
The invention patent with the patent number of CN201510295509.8 provides a tunable liquid cell laser, wherein two optical fiber tweezers are needed to capture cells simultaneously, and signal light is collected by adopting a mode that one end of an optical fiber outputs light and the other end of the optical fiber receives light; the invention patent with the patent number of CN201510267391.8 provides a liquid drop whispering gallery mode laser and a manufacturing method thereof, wherein input light needs to be coupled into an annular core in a mode of single-mode fiber and annular core fiber fused tapering, and liquid drops can transmit signal light only by contacting with micro-nano fiber; the invention patent with the patent number of CN201510271055.0 provides a multi-wavelength droplet laser, wherein, as the same as the previous patent, each droplet needs to be contacted and output with a micro-nano optical fiber, the method undoubtedly increases the difficulty of the device, as is known, the size of the micro-nano optical fiber is only a few micrometers, the micro-nano optical fiber is very easily influenced by the external environment, and the cleanness of the surface of the optical fiber is difficult to keep for a long time, and the patent needs a plurality of droplets to be linearly arranged, which means that the micro-nano optical fibers need to be linearly distributed, and because the size of the droplets is smaller, the method also provides a very high requirement for experimental operation. The invention patent with patent number 201810169543.4 proposes a living body single cell multifunctional spectrometer based on coaxial double waveguide fiber, the cell glimmer hand mentioned in the patent is similar to the principle of capturing cells by the fiber used in the patent, and also captures by multi-core, but the device structure and the function of the central fiber core are different, the invention not only enriches the structure of the fiber, but also increases various novel functions of the fiber, and simultaneously changes the processing structure of the fiber end of the fiber optical tweezers, thereby changing the position of capturing the optical field of the cell, and making the operability of the experiment stronger. Compared with the invention, the novel multi-core optical fiber cell laser system with the stretching function, which is provided by the invention, has the advantages that the novel structure of the optical fiber comprises a middle fiber core and a plurality of fiber cores distributed in different structures, a plurality of functions of cell capture, cell posture stretching, gain material excitation, optical signal receiving and the like are integrated in the same optical fiber, and the capture optical field of the optical fiber tweezers on the cells is optimized.
Under the above background, the present invention provides a novel multi-core fiber laser system with stretching function. On one hand, the optical fiber can transmit different optical wave bands through a plurality of fiber cores, so that the capture of cells, the distribution of an operating optical field and the excitation of cell laser are completed, and the optical fiber has the characteristics of optical field regulation and excitation; on the other hand, the distribution intensity of the optical trap can be adjusted by regulating and controlling the intensity of the captured light, so that the stretching degree can be controlled, and the excitation light path and the micro resonator can be accurately butted. The device adopts the novel multi-core optical fiber, has the characteristic of multi-optical-path high integration, has the characteristics of small volume and flexibility, provides an important multifunctional tool for the exploration and research of life science problems of living unicells similar to 7, is a novel laser under the development trend of interdisciplinary fusion, and has very important significance and value.
Disclosure of the invention
The invention aims to provide a multi-core optical fiber cell laser system with a stretching function, which can be used for single cell capture and cell laser spectrum measurement.
A multi-core optical fiber cell laser system with stretching function, the 'optical fiber-cell' laser is mainly composed of the following four parts: (1) the end of the multi-core optical fiber with a novel structure is polished into a rotationally symmetrical double-angle cone frustum shape to prepare the optical fiber optical tweezers; (2) the micro optical resonant cavity is internally provided with a gain medium with an optical amplification function and can be distributed in a sphere, outside the sphere or on the surface layer of a spherical shell; (3) comprises a light source which can provide cell capture photodynamic with the wavelength of 980nm and a gain medium excitation light source with the wavelength of 460-670 nm; (4) a cell output laser detection spectrometer. In the laser system: the capture light beam is led out from the capture light source 2 by the standard single-mode fiber 6, is divided into two paths of light by the 1 xN coupler 3, and respectively enters other fiber cores of the multi-core fiber 9 except the middle core after passing through 4-2 to 4-N attenuators and the multi-core fiber splitter 8. The excitation beam is directed from the excitation source 1 by a standard single mode fibre 6, through an attenuator 4-1 and a circulator 5 into a multi-core fibre splitter 8 and then into the intermediate core of a multi-core fibre 9.
The sample cell is filled with liquid of cells and is stabilized on the object stage 11, the optical fiber tweezers 10 are immersed in the sample cell for realizing the cell capture and control of the multi-core optical fiber probe, and the precise displacement operation process is carried out real-time imaging through an imaging module consisting of the image amplification system 12, the CCD13 and the computer 14. Meanwhile, the detected cell laser signal enters the spectrometer 7 through the three-terminal circulator 5 to be received. The cells in the liquid are captured by the optical fiber tweezers 10 with the rotationally symmetric cone frustum-shaped optical fiber ends, the adjustment of the positions and the stretching of the postures of the cells are realized through the combined control of the capturing force of the multiple fiber cores of the optical fiber tweezers, so that the excitation light emitted by the middle fiber core and the resonant microspheres are accurately butted, the conditions of providing an excitation light source for the microsphere resonant cavity and outputting resonance enhanced fluorescent signals to be detected are met, and the self-assembly is realized to form a novel optical fiber-cell laser. In the system structure of the above "fiber-cell" laser, a plurality of waveguides perform the functions of photodynamic capturing and stretching of cells, and the middle fiber core waveguide provides an excitation light for the captured cells, and the emitted excitation light is coupled with the stretched microspheres in the cells, so as to realize the resonance excitation of the microspheres and the output of laser signals, and complete the sensing and measurement of parameters such as tiny change of refractive index of cytosol in the cells, as shown in fig. 1.
The multicore fiber 9 used in the present invention has a central core waveguide and a plurality of side core waveguides of different shape distributions. The multiple core waveguides are used for transmitting the capture light beam and accurately controlling and adjusting the cell posture, the middle core is used for transmitting the excitation light beam, and as shown in fig. 2, the structure and refractive index distribution schematic diagram of the multi-core fiber and the type of light introduced into each core waveguide are shown.
The trapping beam is injected into the cores of the multi-core fiber 9 through the coupler 3 and the attenuators 4-1 to 4-N. The method is that a rotationally symmetrical reflection multi-angle frustum structure formed by fine grinding is prepared at the fiber end of a multi-core fiber to serve as the optical tweezers 10, and the optical tweezers are used for refraction and convergence of transmitted light beams in the multi-core fiber to form an optical trapping potential well. The capture light beams transmitted in other fiber cores of the multi-core fiber except the middle fiber core can be reflected and focused through the circular truncated cone structure, so that a deeper capture potential well is realized for cell capture. In order to realize the stable capture and excitation of cells, the optical tweezers can be prepared by an optical fiber end polishing technology, such as a rotationally symmetric multi-angle cone frustum structure, as shown in fig. 4. In order to satisfy refractive convergence, the frustum base angle α needs to satisfy: alpha is alpha<arcsin(n1/n2)，n1Refractive index of the liquid environment in which the cell is located, n2Is the core index. In order to increase the distance between the foci, the range over which the cells can be stretched is made larger, which can be achieved by changing the rotationally symmetrical cone-frustum structure. The tangent cone frustum structure (fig. 3(a)) is processed into a multi-angle cone frustum structure (fig. 3(b)), and the distance between two focus points can be further increased through the structural change of the tangent plane, so that the operable range of the cell can be increased.
In the process of capturing cells by using an optical gradient force potential well emitted by the processed optical fiber tweezers (shown in fig. 4) with the multi-angle cone frustum structure, each waveguide can regulate and control light intensity through a respective independent attenuator, so that the cells can be captured, and the stretching operation of the cells in the radial direction Z of the position (X, Y, Z) can be realized. The force profile of the captured cell is shown in fig. 5, where the focal point of the capture beam in the core corresponds to the bottom of the gradient force well,on XY plane F1-F4Reach an equilibrium state and capture the force F with the light field emitted by each core5And F6Balance each other to accomplish stable stretching of the cells.
The excitation beam is injected into the middle core of the multi-core fiber 9 through the attenuator 4-1, the circulator 5, and the multi-core fiber splitter 8. Excitation light beams transmitted in the middle fiber core of the multi-core fiber can directly pass through the end face of the truncated cone structure to realize the excitation of the captured cell laser, and the method comprises the following steps: after a cell is captured by a light beam emitted by the multi-core fiber, the energy of two light focusing points is adjusted, the microsphere is subjected to unevenly distributed optical trapping force and stretched into a micro-ellipsoid shape, when excitation light is excited, the micro-ellipsoid can be used as an optical Fabry-Perot microcavity, and an excited laser signal is limited in a micro-nano resonant cavity. The two ends of the long axis of the micro ellipsoid are equivalent to high-reflection cavity mirrors with two parallel surfaces, optical signals are transmitted back and forth between the cavity mirrors, light transmitted near the axis is reflected back and forth to form standing waves, and the standing waves are amplified through feedback light to form the laser output cavity. However, in general, in an experiment, the parallel arrangement of two cavity mirrors is not absolutely stable, and is extremely sensitive to the tiny vibration of the surrounding environment or other external conditions, if the resonant cavity deflects at a tiny angle, the optical signal transmitted back and forth in the resonant cavity is easily overflowed out of the resonant cavity after being reflected for many times, so that a low-threshold laser such as a cell laser needs a relatively stable fabry-perot microcavity, and a micro ellipsoid is controlled by the optical field distribution of a central symmetric structure, so that the stretched micro ellipsoid becomes a regular ellipsoid, and the theoretical calculation of the stable conditions can be performed in an ABCD matrix manner:
Figure BDA0002058277910000061
the stability condition to be satisfied is
Figure BDA0002058277910000062
At the baseIn the cell laser resonant cavity of the Fabry-Perot cavity, light respectively passes through the cavity mirror and the cell twice, and an incident light transmission matrix M in the cavity1Is composed of
Figure BDA0002058277910000063
Matrix M is transmitted to reflection ray2Is composed of
Figure BDA0002058277910000064
In the above formula, R is the stability condition of the resonant cavity calculated by the cell radius, ncellIs the effective refractive index of the intracellular material, n0Is the refractive index of the cell's external environment. The cell laser outputs weak laser signals, and the threshold value of the cell laser is lower than that of the traditional laser, so that the cell laser also meets the application requirements in the field of future biological medicine, and the threshold value is an important parameter for the cell laser. The typical gain provided by a unit length of phosphor material is
Figure BDA0002058277910000065
Where N is the molecular concentration of the fluorescent material, τ is the fluorescence lifetime, c is the propagation speed of light in vacuum, σ isssThe absorption cross section corresponding to the laser wavelength. Wherein the content of the first and second substances,
Figure BDA0002058277910000066
Figure BDA0002058277910000067
where n is the refractive index of the laser medium, J (z) is a function of the variation of the pump intensity in the z-axis direction, σ0For the absorption cross section corresponding to the pumping wavelength, h upsilon is photon energy, E (lambda) isLinear function of spontaneous emission, and
Figure BDA0002058277910000068
wherein phi is the quantum yield. The light intensity of the signal light which returns once in the cavity can pass through
Figure BDA0002058277910000069
And (6) obtaining. The threshold of the cell laser is calculated in such a way that the intensity of the light going back and forth in the cavity is equal to the initial intensity when the threshold is reached, but is usually determined experimentally by fitting a curve to the measured data. Fig. 6 is a schematic diagram of the operating principle of the fabry-perot resonator microsphere, and the mode of limiting the optical field can make the intensity of light in the cavity very high, and can effectively improve the pumping efficiency, thereby greatly reducing the laser threshold and meeting the application requirements in cell biology to a great extent.
The multicore fiber splitter 8 referred to therein is understood to be a device which is able to split an outgoing light beam into a plurality of different splitting branches, each of which in turn can be individually controlled by an attenuator 4, and which can be coupled into the individual cores of the multicore fiber.
As shown in FIG. 1, in order to meet the requirements of various sensing measurements, the invention can replace microspheres with single biological cells, thereby realizing the cell laser based on the multi-core optical fiber.
The invention has at least the following obvious advantages:
(1) a cell laser is provided. Compared with other single-cell mass lasers, the laser provided by the invention has the characteristics of no wound and capability of realizing real-time laser spectrum detection.
(2) The invention integrates single cell capture technology, stretching and cell laser into the same multi-core fiber, and can provide abundant cell structure and chemical composition information. Therefore, the invention can realize the analysis of single cells in all directions and multiple functions.
(3) The optical fiber probe provided by the invention integrates a plurality of operation functions into one optical fiber, has the characteristics of high integration level and high operation flexibility, and can realize in-vivo rapid analysis of living unicells.
(IV) description of the drawings
FIG. 1 is a schematic diagram of an apparatus for a multi-core fiber laser system with stretching function.
Fig. 2 is a schematic diagram of the structure and refractive index profile of a multicore fiber, and the type of light passing through each core waveguide.
FIG. 3 is a schematic diagram of the optimization of the shape of the optical fiber taper: (a) optimizing a front optical fiber cone round table; (b) and optimizing the cone frustum of the rear optical fiber.
FIG. 4 is a schematic view of a rotationally symmetric multi-angle cone frustum structure of a multi-core fiber end.
FIG. 5 is a schematic diagram of the force applied to the microsphere when two light beams emitted from the end of the multi-core fiber are combined into an optical field.
FIG. 6 is a diagram of a laser signal spectrum received according to the Fabry-Perot resonant microcavity operating principle.
Fig. 7 is a schematic diagram of an apparatus of a five-core fiber-optic cell laser system with a stretching function.
FIG. 8 is a schematic diagram of the working principle of laser measurement of single living cells by a five-core fiber laser based on linear distribution.
FIG. 9 is a schematic diagram of the working principle of laser measurement of single living cells by a seven-core fiber laser based on triangular distribution.
(V) detailed description of the preferred embodiments
Cell biology is known to remain an important discipline in the life sciences field, and is the foundation supporting the development of biotechnology. Although cells have been found for over 300 years, human beings do not currently gain a complete and clear understanding of the mechanism by which cells operate at the global level. Cell biology is the fundamental rule for studying the life activities of cells from their different structural levels. The method and the concept of the modern scientific and technical achievement are applied to reveal the information in the cell on the cell level, and the method and the concept are one of important ways for acquiring the biological information of the cell.
The living single cell technology is the leading edge of the current biological technology, can provide scientists with a lot of new biological information, can not only check the conclusion of the past classical method, but also can discover a lot of new rules. For example, single cell technology first allows scientists to test whether there is really a cell mean indicator, i.e., whether past multi-cell research methods are really reliable, and how accurate such traditional research techniques are. In addition, single cell detection methods can provide very rich information, sometimes unanticipated, or historically masked by statistical results. The single cell research can not only make up for the hidden and omitted important information caused by the group cell sampling in the past, so that the result of the omics research is more objective and comprehensive, but also can possibly obtain new phenomena and new rules which are not discovered in the life science research, thereby having particularly important significance for the life science research.
For decades, researchers have mainly developed analyses of cell populations. An important prerequisite for carrying out such studies is that the individual cells that make up these cell populations (e.g., normal tissue cells and tumor cells) are considered to be more or less homogeneous or identical, with the results obtained being an average of the characteristics of these cell populations. In recent years, single cell analysis techniques have been increasingly highlighted as the phenomenon of cellular heterogeneity has been revealed. However, single cell analysis faces a number of problems. The most challenging is the difficulty of sensitivity to meet the requirements, both for monospecific macromolecules and for molecular analysis at the omics level, with the difficulty that single cell extracts are of low quality and difficult, if not impossible, to analyze.
Due to limitations in sensitivity, sample volume, etc., a large number of cells are mainly used as research objects in general life science research. However, there is a significant microscopic heterogeneity (heterogeneity) between different individuals of the same cell, and it is difficult to reflect the life activity rule at a single cell level based on the experimental results of a large number of cells. Therefore, the analysis based on living single cells can reveal the nature and the rule of life activities at a deeper level, and provide more reliable scientific basis for exploring the cause, development and treatment of serious diseases.
The present invention will be specifically described below by taking a multicore fiber cell laser system having a stretching function as an example.
Example 1: laser measurement of single living cells by a cell laser based on a linearly distributed five-core optical fiber:
fig. 7 is a schematic diagram of an apparatus for a multi-core fiber-optic cell laser system with stretching, in which: the capture light beam is led out from the capture light source 2 by the standard single-mode fiber 6, is divided into two paths of light by the 1 xN coupler 3, and respectively enters other fiber cores of the multi-core fiber 9 except the middle core after passing through 4-2 to 4-N attenuators and the multi-core fiber splitter 8. The excitation beam is directed from the excitation source 1 by a standard single mode fibre 6, through an attenuator 4-1 and a circulator 5 into a multi-core fibre splitter 8 and then into the intermediate core of a multi-core fibre 9. The sample cell is filled with liquid containing cells and is stabilized on the object stage 11, the optical fiber tweezers 10 are immersed in the sample cell for realizing the capture and control of the multi-core optical fiber probe on the cells, and the precise displacement operation process is carried out real-time imaging through an imaging module consisting of the image amplification system 12, the CCD13 and the computer 14. Meanwhile, the detected cell laser signal enters the spectrometer 7 through the three-terminal circulator 5 to be received. The cells in the liquid are captured by the optical fiber end optical tweezers 10 with the rotationally symmetrical cone frustum shape, and the cell position adjustment and posture stretching are realized through the combined control of the capturing force of the cone multi-fiber core of the optical fiber optical tweezers, so that the excitation light emitted by the middle fiber core and the resonant microspheres are accurately butted, the conditions of providing an excitation light source for the microsphere resonant cavity and outputting a resonance enhanced fluorescent signal to be detected are met, and the self-assembly becomes a novel optical fiber-cell laser. In the system structure of the optical fiber-cell laser, a plurality of waveguides play roles in performing photodynamic capturing and stretching on cells, the middle fiber core waveguide provides exciting light for the captured cells, and the emitted exciting light is coupled with the stretched microspheres in the cells, so that resonance excitation of the microspheres and output of laser signals are realized, and sensing and measurement of parameters such as tiny change of refractive index of cytosol in the cells are completed.
As shown in FIG. 8, HEK293 human embryonic kidney 15 was used as the cell, which is a mammalian cell commonly used for transfection in biology and has a diameter of 13.8 μm, and the gain medium green fluorescent protein molecule was organically integrated with the cell. When the system works, the wavelength of the capture light beam 17 is 980nm, the wavelength of the excitation light beam 18 is 480nm, and the two light beams are respectively introduced into the middle fiber core and other fiber cores of the multi-core optical fiber 9. The 980nm trapped light enters the fiber core light beam to realize light reflection on the cone frustum, the light beam is converged into a light trap at a distance from the end face of the optical fiber, and the cell posture is adjusted by respectively adjusting the light intensity in the fiber core to accurately control the trapped cells. 480nm of excitation light 18 is introduced into the middle fiber core, when the position adjusted by the cell meets the oscillation condition of excitation light emitted by the gain material micro ellipsoid 16 and the middle fiber core waveguide in the cell 15, a laser signal generated by excitation of the gain medium is continuously amplified through the microsphere resonant cavity, when the gain is larger than the total loss in the cavity, laser output is formed, the laser signal 19 returns through the middle fiber core where the excitation beam is located and is received, then is transmitted to the circulator 5, and finally, a feedback path is completed through the spectrometer 7, so that a cell laser spectrogram is obtained.
Example 2: laser measurement of single living cells by a cell sensor based on a triangular distribution seven-core optical fiber:
the system is the same as the cell sensor device of the linearly distributed five-core optical fiber in composition, and as the number and the distribution of the fiber cores are changed, a capture beam 17 and an excitation beam 18 in the system respectively enter a multi-core optical fiber branching unit 8 through a 1 x 6 coupler 3 and are respectively injected into the corresponding fiber cores, wherein the fiber core bcdefg is a capture function fiber core, the injected capture beam 17 is the capture beam, the fiber core a is the excitation function fiber core, and the injected excitation beam 18 is the excitation beam. The cell is HEK293 human embryonic kidney cell 15, when the system works, the wavelength of the captured light beam 17 is 980nm, the wavelength of the excitation light beam 18 is 480nm, the other fiber cores except the middle fiber core can achieve the function of accurately controlling and adjusting the cell posture of the captured cell through independently controlling the attenuator 4, and meanwhile, the middle fiber core is used for exciting cell signal light. Laser signals 19 in the cell are returned and received through the middle fiber core where the exciting light beams are located, then transmitted to the circulator 5, and finally a feedback path is completed through the spectrometer 7, so that a cell laser spectrogram is obtained, as shown in fig. 9.

Claims (5)

1. A multi-core optical fiber cell laser with stretching function is characterized in that: the laser is an optical fiber-cell laser system and mainly comprises the following four parts: (1) the end of the multi-core optical fiber with a novel structure is polished into a rotationally symmetrical double-angle cone frustum shape to prepare the double-optical-trap optical fiber optical tweezers; (2) the micro optical resonant cavity is internally provided with a gain medium with an optical amplification function; (3) a light source capable of providing cell capture photodynamic and a gain medium excitation light source; (4) a detection spectrometer for outputting laser to the cell;
in the "fiber-cell" laser system: the capture light beam is led out from a capture light source (2) by a standard single-mode fiber, is divided into N paths of light by a 1 xN coupler (3), and respectively enters other fiber cores of the multi-core fiber (9) except the middle core after passing through a second attenuator (4-2) to an Nth attenuator (4-N) and a multi-core fiber splitter (8); the excitation light beam is led out from an excitation light source (1) by a standard single mode fiber, enters a multi-core fiber splitter (8) through a first attenuator (4-1) and a three-terminal circulator (5), and then enters a middle fiber core of a multi-core fiber (9); the sample cell is filled with liquid of cells and is stabilized on an object stage (11), the double-optical-trap optical fiber optical tweezers (10) are arranged in the sample cell, and the multi-core optical fiber probe is used for capturing the cells and controlling the stretching deformation by adjusting the two optical traps; the precise displacement operation process is carried out real-time imaging through an imaging module consisting of an image amplifying system (12), an imaging system CCD (13) and a computer (14); meanwhile, the detected cell laser signals enter a spectrometer (7) through a three-terminal circulator (5) for receiving; the cells in the liquid are captured by the end fiber optical tweezers (10), and the combined control of the capturing force of the multi-fiber cores of the double-optical trap fiber optical tweezers is adopted to realize the adjustment of the position and the stretching of the posture of the cells, so that the excitation light emitted by the middle fiber core is accurately butted with the micro optical resonant cavity, the conditions of providing an excitation light source for the micro optical resonant cavity and outputting a resonance enhanced fluorescence signal to be detected are met, and the cells are self-assembled into a novel fiber-cell laser; in the system structure of the fiber-cell laser, the double-optical trap optical tweezers play a role in performing photodynamic capturing and stretching on cells; the middle fiber core waveguide provides an exciting light for the captured cell, and the emitted exciting light is coupled with the stretched micro optical resonant cavity in the cell, so that the resonance excitation of the micro optical resonant cavity and the output of a laser signal are realized, and the sensing and the measurement of parameters such as the tiny change of the refractive index of cytosol in the cell are completed.
2. The multi-core fiber laser with stretching function as claimed in claim 1, wherein: the multi-core optical fiber is any one of a five-core optical fiber with linear distribution, a seven-core optical fiber or a thirteen-core optical fiber with triangular distribution, a nine-core optical fiber or a thirteen-core optical fiber with square rhombus distribution, and a thirteen-core optical fiber or a seventeen-core optical fiber with annular distribution.
3. The multi-core fiber laser with stretching function as claimed in claim 1, wherein: the geometric shape of the micro optical resonant cavity is a central symmetric body, has elasticity and is easy to deform under stress, and a certain gain medium is contained in the micro optical resonant cavity.
4. The multi-core fiber laser with stretching function as claimed in claim 1, wherein: the micro optical resonant cavity is a spherical single cell, a biological particle existing in a cell or a regular elastic spherical particle placed in a cell.
5. The multi-core fiber laser with stretching function as claimed in claim 1, wherein: two focuses formed by a plurality of fiber cores of the multi-core fiber form two optical traps, and the micro optical resonant cavity is stretched under stress and is changed into an ellipsoid from a spherical shape.
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