CN110071417A - Three core fibre cell laser of coaxial Crossed Circle with stretch function - Google Patents
Three core fibre cell laser of coaxial Crossed Circle with stretch function Download PDFInfo
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Abstract
The present invention is to provide a kind of three core fibre cell Optical Maser System of coaxial Crossed Circle with stretch function.It is somebody's turn to do " optical fiber-cell " laser to be mainly made of following four part: (1) there is new structural coaxial three core fibre of Crossed Circle, which, at the multi-angle cone truncated cone-shaped of rotational symmetry, is prepared into optical fiber optical tweezers by rubbing down；(2) microspheroidal optical resonator, the intracavitary gain media for optical amplifier function；(3) the photodynamic light source of cell capture and gain media excitation light source be can provide；(4) the detecting light spectrum instrument of cell output laser.The output spectrum of cell interior microsphere optical resonant cavity is very sensitive to the variation that the environmental physics parameter such as cell interior cytosol is faint, can be measured by the amplification laser signal that multicore tapered optical fiber exports.The present invention can be used for unicellular capture, the measurement of cell laser spectrum, can be widely used for Manipulation of single cells, sensing, measurement and analysis technical field.
Description
(1) technical field
The present invention relates to a kind of three core fibre cell Optical Maser System of coaxial Crossed Circle with stretch function, can use
In cell capture, the measurement of cell laser spectrum and cell laser self assembly, it is particularly suitable for Manipulation of single cells, measurement and analysis
Technical field.
(2) background technique
Nineteen sixty American scientist T.H. plum is graceful et al. successfully to create First ruby crystal laser in the world,
A. Jia Wen in 1961 et al. successfully develops He-Ne laser, and R.N. Hall in 1962 et al. develops gallium arsenide semiconductor laser
Device.The birth of laser indicates the direction of the launch, phase, frequency and the polarization etc. of the capable multiple photons of regulation of people, makes one
Higher level has been reached to the understanding of light and application.Laser shows beyond imagination in micromation and cross discipline direction
Application value, therefore this field of light stream body laser is just come into being.Light fluid is respectively unique in conjunction with optics and fluid
Advantage and the novel research field of a multi-crossed disciplines that is formed, concept mentioned in 2003 by university, California Institute of Technology
Out, living organism has very wide because there are natural liquid environments in fields such as biomedical diagnostics, sensor measuring and imagings
General application prospect.
Cell laser is a kind of special light stream body laser (laser and optoelectronics progress, cell Laser Study
Progress and application summary, 2018,55:120001), the liquid environment of organism existence can be simulated in vitro or directly in life
In object, the laser output of cell is realized under the excitation of outside energy.It is common compared in current biomedical every field
The fluorescence signal detection method arrived has its own unique advantage by the way of laser signal detection.Firstly, laser signal
It is the spontaneous emission light that excited radiation light is different from fluorescence signal, it is good being had after the signal of resonant cavity amplification feedback
Directionality；Secondly, the signal energy of work particle output is much higher than fluorescence signal when driving source laser signal is higher than threshold value,
So the resolution ratio of laser signal detection and sensitivity can also be much higher than fluorescence detection, also, laser signal output spectrum line width
Spectrum width is extremely narrow compared with the fluorescence spectrum of luminescent material, is conducive to be timely responded in sample detection process in this way.Cell swashs
Common gain media is generally fluorescent material in light device, such as fluorescin (NATURE PHOTONICS, Single-cell
Biological lasers, 2011,5:406-410), fluorescent dye (Bio-switchable optofluidic lasers
Based on DNA Holliday junctions, 2012,12 (19): 3673-3675), fluorescein, quantum dot, vitamin,
And fluorescence resonance energy transfer equity, gain media and cell are subjected to organic combination, absorb the increasing emitted after excitation energy
Beneficial signal amplifies through the continuous oscillatory feedback of optical resonator, when gain is greater than intracavitary total losses, will form laser output.
In June, 2001, Gather of Harvard University et al. allow human embryonic kidney cells to launch laser signal (NATURE
PHOTONICS, Single-cell biological lasers, 2011,5:406-410), in device excitation light source need by
Image enhancement system focusing makes hot spot be contracted to individual cells size, and it is bigger using two panels high reflection mirror to bond out a space
In the Fabry-Perot cavity of cell size, to limit cell in the position of excitation light, so the device volume is huge
Greatly, the direction and position of spatial excitation light are not easy to adjust to unicellular, and the method that can only be limited by free surrounding space is come
Capture cell.2015, the Humar et al. of medical college, Harvard University had developed a plurality of cells based on Whispering-gallery-mode microcavity and swashs
Light device (NATUREPHOTONICS, Intracellular microlasers, 2015,9:572-576), it was demonstrated that natural
It can also realize that laser exports into the cell, artificially be placed in a regular circle shapes fat drips in the cell as Whispering-gallery-mode, output
Signal is coupled to spectral detector through 200 μm of core diameter of multimode fibre, but the device volume is larger, and receives signal and used
Optical fiber it is thicker, due to micro- manipulation function such as can not precisely capture to cell, so that excitation beam irradiating cell this operation
What is become is inaccurate, and the micro-displacement of cell in a liquid, which will lead to excitation light beam, can not accurately be coupled into fat drips, makes gain
Signal can not continuously enhance, while also increase the operation difficulty of experiment.
Surface force about optical induction leads to the capture and stretching of cell, and the common method to cell tensile has, and leads to
Crossing the transmitting of optics stretcher combination microfluid can be such that single suspension cell deforms by the surface force of optical induction, pass through two beams
Contrary spatial light, allow cell in microfluidic channel captured and deformed by divergent laser beam (Biophys,
The optical stretcher:a novel laser tool to micromanipulate cells,81:767–784,
2001).Other methods are connect in addition, passing through the processed silicon oxide pellets of protein coating with two by erythrocyte,
In bead it is fixed on a glass, another bead is captured by optical tweezer, and in the moving process of ligh trap, bead is with optical tweezer
Movement and move, to achieve the effect that erythrocyte is stretched (Acta Mater, Large deformation of
living cells using laser traps,52,1837–1845,2004).In addition to this also have directly using glass or
The tip of metal and cell contact are measured the viscosity of cell by the stretching of the distance between two tips and curvature, equally may be used
To carry out stretched operation (Biophysical Journal, Creep Function of a Single Living to cell
Cell,88:2224-2233,2005).These methods include the equipment of two opposite directions, including photodynamic and machinery moves
Power, contact or non-contacting stretched operation are carried out to the two sides of cell, wherein can also require micro-fluidic due to light source etc.
The other equipment such as channel guarantee that the cell being stretched can only be passed through always in the environment easily survived by spatial light
Microfluidic channel operates, it is proposed by the invention based on the cell laser of novel optical fiber structure by cell capture, stretching, swash
The functions such as hair and reception integrate, and greatly reduce the number and size of required instrument, reduce experimental procedure,
Reduce experiment difficulty.
The patent of invention of Patent No. CN201510295509.8 proposes a kind of tunable liquid cell laser, the patent
It is middle that two optical fiber optical tweezers is needed to carry out capture operation to cell simultaneously, and received using one end optical fiber output opposite direction other end optical fiber
Mode collecting signal light；The patent of invention of Patent No. CN201510267391.8 proposes a kind of drop Whispering-gallery-mode laser
Device and preparation method thereof needs that optical coupling will be inputted by way of single mode optical fiber and toroidal cores optical fiber fused tapering in the patent
Into in toroidal cores, drop, which also needs to contact with micro-nano fiber, to go out signal optical transport；Patent No.
The patent of invention of CN201510271055.0 proposes a kind of multi-wavelength drop laser, due to needing to multiple drops in the patent
Excitation-detection is carried out, identical with a upper patent, each drop is required to contact output, this method with a micro-nano fiber
Undoubtedly increase the difficulty of device, it is well known that the size of micro-nano fiber only has several microns, is highly prone to the shadow of external environment
It rings, and is difficult to keep the cleaning of optical fiber surface for a long time, and need multiple drops linearly to arrange in the patent, also just mean
Need multiple micro-nano fiber linear distributions, since the size of drop is smaller, this also proposes high requirement to experimental implementation.
The patent of invention of Patent No. 201810169543.4 proposes the multi-functional spectrometer of Living single cell based on coaxial double wave guiding fiber,
The cell glimmer hand being previously mentioned in the patent is close with the capture cell principle of optical fiber used in this patent, is equally to use toroidal cores
It is captured, but apparatus structure and central core function are had nothing in common with each other, the present invention not only enriches the structure of optical fiber, also increases
The various new function of optical fiber, while the processing structure of optical fiber optical tweezers optical fiber end is changed again, and then is changed and caught to cell
The position for obtaining light field improves the coupled modes of incident light and toroidal cores compared with the method for side throwing coupling, makes grasping for experiment
The property made is stronger.It is proposed by the present invention based on novel three core of coaxial Crossed Circle with stretch function compared with the above patent of invention
Optical fiber cell Optical Maser System, the new structure of optical fiber include a middle fiber core and two coaxial toroidal cores, and cell is caught
Obtain, cell posture stretches, the excitation of gain substance and optical signal receive etc., and multiple functions are integrated in the same optical fiber, and optimize
Capture light fields of the optical fiber optical tweezers to cell, the invention is by the analysis detection to Living single cell and to disclosing vital movement
Essential laws provide more reliable scientific basis.
The present invention proposes a kind of novel three core fibre cell of coaxial Crossed Circle with stretch function under background above
Optical Maser System.On the one hand it can transmit different optical bands by annular fibre core, to complete the capture of cell, operation light
The distribution of field and the excitation of cell laser, therefore have the characteristic of light field regulation and excitation；On the other hand, light is captured by regulation
Intensity, adjustable ligh trap distribution intensity keep excitation light path and resonance microballoon complete so as to control the degree that microballoon is stretched
At accurate docking.This device uses three core fibre of novel coaxial Crossed Circle, has the characteristics of multi-pass Highgrade integration, has
The volume of very little and flexible flexible nature, for the Living single cell similar to microballoon life science problem exploration with grind
Study carefully and provide important multi-purpose tool, the present invention is a kind of new laser under subject crossing fusion development trend, therefore
It has a very important significance and is worth.
(3) summary of the invention
The purpose of the present invention is to provide a kind of three core fibre cell laser system of coaxial Crossed Circle with stretch function
System can be used for unicellular capture, the measurement of cell laser spectrum.
A kind of three core fibre cell Optical Maser System of coaxial Crossed Circle with stretch function, should " optical fiber-cell " laser
Device is mainly made of following four part: (1) having new structural coaxial three core fibre of Crossed Circle, the optical fiber end is by rubbing down
At the cone truncated cone-shaped of rotational symmetry, it is prepared into optical fiber optical tweezers；(2) microspheroidal optical resonator, it is intracavitary that there is optical amplifier function
The gain media of energy can be distributed in ball, ball is outer or spherical shell surface layer；It (3) include that can provide the cell capture that wavelength is 980nm
The gain media excitation light source of photodynamic light source and wavelength in 460-670nm；(4) the detecting light spectrum instrument of cell output laser.
In the Optical Maser System: capture light beam is drawn by standard single-mode fiber 6 from capture light source 2, and being divided to via 1 × 2 coupler 3 is two
Lu Guang, respectively by respectively enteing coaxial three core fibre 9 of Crossed Circle again after 4-2 and 4-3 attenuator and multi-core optical fiber splitter 8
Two of them annular fibre core 9-1 and 9-2 in.Excitation light beam is drawn by standard single-mode fiber 6 from excitation light source 1, through overdamping
Device 4-1 and circulator 5 enter multi-core optical fiber splitter 8, subsequently into the middle fiber core 9-3 of coaxial three core fibre 9 of Crossed Circle.
Liquid containing cell is filled in sample cell and is stablized on objective table 11, the sample cell that optical fiber optical tweezers 10 are immersed in
In, for realizing coaxial three core fibre probe of Crossed Circle to cell capture and manipulation, accurate displacement operation process passes through image
The image-forming module that amplification system 12, CCD13 and computer 14 form carries out real time imagery.At the same time, the cell detected swashs
Optical signal enters spectrometer 7 by three end circulators 5 and receives.Cell in liquid is by with rotational symmetry cone truncated cone-shaped optical fiber
The optical fiber optical tweezers 10 at end capture, and combine manipulation by the force trapping of optical fiber optical tweezers toroidal cores 9-1 and 9-2, realize to cell position
Adjustment and posture stretching so that the exciting light that is emitted of middle fiber core 9-3 is accurately docked with the completion of resonance microballoon, satisfaction
Excitation light source is provided to microsphere resonator and exports the condition of resonance enhancing fluorescence signal to be detected, so that being self-assembled into is one
A novel " optical fiber-cell " laser.In the system structure of above-mentioned " optical fiber-cell " laser, two of them cone circle
Ring waveguide plays the role of carrying out the capture of light power and stretching to cell, and middle fiber core waveguide provides captured cell
One exciting light, the exciting light of sending is coupled with the microballoon after intracellular be stretched, to realize the resonance to microballoon
Sensing and measurement to parameters such as cell interior cytosol refractive index minor changes, such as Fig. 1 are completed in the output of excitation and laser signal
It is shown.
Three core fibre 9 of coaxial Crossed Circle of the present invention has a middle fiber core waveguide 9-3 and two coaxial point
The annular core wave guide 9-1 and 9-2 of cloth, the distance between two toroidal cores are related with the diameter of toroidal cores.Two of them toroidal cores wave
It leads and is used for transmission capture light beam and precisely manipulation adjustment cell posture, intermediate core is then to be used for transmission excitation beam, as shown in Figure 2
It is the class of be passed through light in the structure and index distribution schematic diagram and each core waveguide of coaxial three core fibre of Crossed Circle
Not.
Capture light beam injects two annulars of coaxial three core fibre 9 of Crossed Circle by coupler 3 and attenuator 4-2 and 4-3
In core 9-1 box 9-2.The wave band light beam is used for the capture of cell, and method is the optical fiber end system using coaxial three core fibre of Crossed Circle
The reflection multi-angle frustum structure of the standby rotational symmetry as made of fine gtinding, as optical fiber optical tweezers 10, for being passed in toroidal cores
The refraction for losing beam is assembled, and is formed light and is captured potential well.The capture light beam energy transmitted in the toroidal cores of three core fibre of coaxial Crossed Circle
Reflection focusing enough is carried out by the frustum cone structure, to realize deeper capture potential well, is used for cell capture.In order to realize to thin
Born of the same parents' stablizes capture and excitation, optical fiber optical tweezers can be prepared by optical fiber end rubbing down technology, such as the multi-angle cone of rotational symmetry
Frustum cone structure, as shown in Figure 4.It is assembled to meet refraction, frustum base angle needs to meet: α < arcsin (n1/n2), n1For cell institute
Locate liquid environment refractive index, n2For toroidal cores refractive index.In order to increase the distance between focus, the range for making cell that can be stretched
It is bigger, for this purpose, can be realized by the method for the cone frustum cone structure of change rotational symmetry.By section cone frustum cone structure
(Fig. 3 (a)) is processed into multi-angle cone frustum cone structure (Fig. 3 (b)), by the structure change of section, can further increase two
The spacing of focus point, what this can increase cell can opereating specification.
The optical gradient forces gesture issued using the optical fiber optical tweezers (shown in Fig. 4) of the multi-angle cone frustum cone structure after processing
During trap captures cell, each waveguide can regulate and control light intensity by attenuator independent, can not only capture thin
Born of the same parents, and can be realized stretching manipulation of the cell on the radial Z of position (X, Y, Z), the process of this manipulation can be by aobvious
The ccd image of micro mirror is observed to feed back its adjustment effect roughly, when optical power becomes larger, the position of nearly two beam focus of cell
Stress becomes larger, and cell is integrally stretched deformation, to further change the optical power size of each light beam according to deformation.Quilt
The stress condition of the cell of capture as shown in figure 5, the focus of the capture light beam in toroidal cores corresponds to the bottom of gradient force potential well,
F on X/Y plane1-F4Reach equilibrium state, and the F issued with toroidal cores5And F6Mutually balance is drawn to complete stablizing for cell
It stretches.
Excitation light beam injects coaxial three core fibre 9 of Crossed Circle by attenuator 4-1, circulator 5 and multi-core optical fiber splitter 8
Middle fiber core 9-3 in.The excitation beam transmitted in the middle fiber core of three core fibre of coaxial Crossed Circle can directly pass through the circle
Realize the excitation of captured cell laser, method in platform structure end face are as follows: after the beam-capturing that cell is issued by toroidal cores is lived,
By the adjusting of two light focus point energy, microballoon is drawn into micro- elliposoidal, works as excitation light by uneven distribution trapping stiffness
When excitation, which can be used as an optics Fabry-Perot micro chamber, and the laser signal after excitation is limited in micro-nano amount
In the resonant cavity of grade.It can be appreciated that the both ends of micro- ellipsoid long axis are equivalent to the anti-hysteroscope of height that two sides is placed in parallel, optical signal
The round-trip transmission between hysteroscope, forms standing wave in the light roundtrip that near axis is propagated, and forms laser by feedback light amplification
Outside output cavity.But since generally two being placed in parallel for hysteroscope are not absolute stabilities in an experiment, to the small of ambient enviroment
Vibration or other external conditions are extremely sensitive, if small angular deflection occurs for resonant cavity, then the round-trip transmission in resonant cavity
Optical signal after multiple reflections easily outside spill cavity, so as this low threshold laser of cell laser need one it is opposite
Stable Fabry-Perot micro chamber, micro- ellipsoid is because the optical field distribution by centrosymmetric structure manipulates, after being stretched
The elliposoidal that can become rule, can carry out the theoretical calculation of stable condition by way of abcd matrix:
The stability condition for needing to meet is
Intracavitary in the cell laser resonator based on Fabry-Perot-type cavity, light will pass through hysteroscope and cell twice respectively,
It is in intracavitary incident ray transmission matrix M1For
Reflection light ability transmission matrix M2For
In above formula, R is the stability condition that cell radius calculates resonant cavity, ncellFor the effective refractive index of intracellular matter, n0
For cell external world ambient refractive index.Cell laser exports faint laser signal, and threshold value is lower than traditional laser, this
Meet the application demand in biologic medical field from now on, so threshold value is an important parameter for cell laser.Generally
The there is provided gain of unit length fluorescent material is
In formula, N is the molecular concentration of fluorescent material, and τ is fluorescence lifetime, and c is the spread speed of light in a vacuum, σssFor laser
Absorption cross-section corresponding to wavelength.Wherein,
In formula, n is the refractive index of laser medium, and J (z) is variation function of the pump intensity in z-axis direction, σ0For pump wavelength institute
Corresponding absorption cross-section, h υ are photon energy, and E (λ) is the linear function of spontaneous radiation, and
φ is quantum yield in formula.The primary signal light light intensity of intracavity round trip can pass through
It acquires.When reaching threshold value, light intensity when intracavity round trip primary light intensity is equal to initial calculates cell in this way
The threshold value of laser, but in an experiment often by the matched curve of measurement data come threshold value.Fig. 6 is that Fabry-Perot is humorous
The mode of vibration chamber microballoon operation principle schematic diagram, this limitation light field can make intracavitary luminous intensity very high, can effectively improve pumping
It transports efficiency and largely can satisfy the application demand in cell biology to greatly reduce laser threshold.
Multi-core optical fiber splitter 8 involved in it can be regarded as that outgoing beam can be assigned to multiple and different light splitting branches
In, and the device that can be coupled into each fibre core of multi-core optical fiber, wherein each light splitting branch again can be single by attenuator 4
Solely control.
The operation principle schematic diagram of three core fibre cell Optical Maser System of coaxial Crossed Circle with stretch function, such as Fig. 1
Shown, in order to meet the needs of various sensing measurements, the present invention can be replaced microballoon with single biological cell, so that base can be realized
In the cell laser of coaxial three core fibre of Crossed Circle.
The present invention at least has obvious advantage below:
(1) a kind of cell laser is proposed.Other slender cytoplasm lasers having proposed are compared to, it is proposed by the present invention
Laser have the characteristics that it is noninvasive, real time laser spectral detection may be implemented.
(2) unicellular capture technique, stretching and cell laser are integrated in coaxial three core of Crossed Circle of same root by the present invention
In optical fiber, eucaryotic cell structure and chemical composition information abundant can be provided.Therefore the present invention can realize comprehensive, multi-functionally
Single celled analysis.
(3) multiple operating functions are integrated within an optical fiber by optical fiber probe proposed by the invention, and optical fiber probe
Have the feature that integrated level is high, operating flexibility is high, can be realized quickly analyzing in body for Living single cell.
(4) Detailed description of the invention
Fig. 1 is the schematic device with the three core fibre cell Optical Maser System of coaxial Crossed Circle of stretch function.
Fig. 2 is institute in the structure and index distribution schematic diagram and each core waveguide of coaxial three core fibre of Crossed Circle
It is passed through the classification of light.
Fig. 3 is optical fiber cone truncated conical shape prioritization scheme: optical fiber cone rotary table before (a) optimizing；(b) optical fiber cone after optimizing
Rotary table.
Fig. 4 is the rotational symmetry multi-angle cone frustum cone structure schematic diagram at coaxial three core fibre fibre end of Crossed Circle.
Fig. 5 is microballoon stress diagram when coaxial three core fibre of Crossed Circle brings out the two light beams combination light field penetrated.
Fig. 6 is to receive laser signal map schematic diagram according to Fabry-Perot resonance microcavity working principle.
Fig. 7 is the operation principle schematic diagram with the three core fibre cell Optical Maser System of coaxial Crossed Circle of stretch function.
(5) specific embodiment
It is known that cell biology is still the important subject in life science, it is support biotech development
Basis.Although the working mechanism to cell on general levels does not obtain the mankind at present it was found that cell more than 300 years
One is obtained completely clearly to recognize.Cell biology be from the different structure level of cell come study cell vital movement base
This rule.With modern science and technology achievement and method, concept, the information of cell interior is disclosed on a cellular level, is cell
One of the important channel that biological information obtains.
Living single cell technology is the forward position of biology at present technology, and many new biology letters can be provided to scientist
Breath, can not only examine over the conclusion of classical way, but also it can be found that many new rules.For example, single cell technology is first
Scientist can be first allowed to check whether really there is cell average value index, that is to say, that whether past many cells research method
How is the levels of precision of genuine reliable and this tradition research technology.In addition, Single cell analysis method can provide it is very rich
Information, be sometimes not expect or information that the past is covered by statistical result.Unicellular research can not only make up
The important information for being blanked and omitting caused by due to group's cell sample is removed, keeps the result of " group is learned " research more objective
With it is comprehensive, and be possible to obtain still not found new phenomenon and new rule in life science, therefore, for life science
Research have especially important meaning.
For decades, researcher is mainly to cell mass deployment analysis.Carrying out the important prerequisite studied in this way is people
The individual cells for thinking to constitute these cell masses (such as normal tissue cell and tumour cell), are almost homogeneous or the same
, eligible result is all the average value of these cell group characters.It is recent years, slender with the announcement of cell heterogeneity phenomenon
Born of the same parents' analytical technology is gradually valued by people.However single cell analysis is faced with many problems.Most challenging is spirit
Sensitivity is difficult to meet demand, is either directed to single specificity macromolecular, or carry out analysis of molecules in group level, all deposits
It is few in unicellular extraction object amount and be difficult to analyze, even can be described as the difficulty that can not be completed.
Due to the limitation of sensitivity and sample volume etc., common life science is mainly with a large amount of cell
Research object.But there is significant microheterogeneity (heterogeneities) between the Different Individual of allogenic cell, based on a large amount of thin
The experimental result of born of the same parents is difficult to reflect the rule of the vital movement on individual cell level.Therefore, the analysis based on Living single cell will
The essence and rule that vital movement is disclosed on deeper level, provide more to probe into cause, development and the treatment of major disease
Reliable scientific basis.
By taking the three core fibre cell Optical Maser System of coaxial Crossed Circle with stretch function as an example, the present invention is carried out specific
Explanation.
Embodiment: the laser measurement of monomer living cells:
Fig. 1 is the schematic device with the three core fibre cell Optical Maser System of coaxial Crossed Circle of stretch function, described
In Optical Maser System: capture light beam is drawn by standard single-mode fiber 6 from capture light source 2, is divided via 1 × 2 coupler 3 for two-way
Light, respectively by respectively enteing coaxial three core fibre 9 of Crossed Circle again after 4-2 and 4-3 attenuator and multi-core optical fiber splitter 8
In two of them annular fibre core 9-1 and 9-2.Excitation light beam is drawn by standard single-mode fiber 6 from excitation light source 1, by attenuator
4-1 and circulator 5 enter multi-core optical fiber splitter 8, subsequently into the middle fiber core 9-3 of coaxial three core fibre 9 of Crossed Circle.Sample
Liquid containing cell is filled in product pond and is stablized on objective table 11, in the sample cell that optical fiber optical tweezers 10 are immersed in, for realizing
Coaxial three core fibre probe of Crossed Circle passes through image enhancement system 12 to cell capture and manipulation, accurate displacement operation process,
The image-forming module that CCD13 and computer 14 form carries out real time imagery.At the same time, the cell laser signal detected passes through three
It holds circulator 5 to enter spectrometer 7 to receive.Cell in liquid passes through by the optical fiber end optical fiber with rotational symmetry cone truncated cone-shaped
Optical tweezer 10 captures, and combines manipulation by the force trapping of cone the toroidal cores 9-1 and 9-2 of optical fiber optical tweezers, realizes to cell position
The stretching of adjustment and posture so that the exciting light that is emitted of middle fiber core 9-3 is completed accurately to dock with resonance microballoon, meet to
Microsphere resonator provides excitation light source and exports the condition of resonance enhancing fluorescence signal to be detected, so that being self-assembled into is one
Novel " optical fiber-cell " laser.In the system structure of above-mentioned " optical fiber-cell " laser, two of them cone annulus
Waveguide is played the role of carrying out the capture of light power and stretching to cell, and middle fiber core waveguide provides one to captured cell
A exciting light, the exciting light of sending are coupled with the microballoon after intracellular be stretched, are swashed to realize to the resonance of microballoon
Sensing and measurement to parameters such as cell interior cytosol refractive index minor changes are completed in the output of hair and laser signal.
As shown in fig. 7, cell here selects HEK293 human embryonic kidney cells 15, this cell be commonly used in biology into
The mammalian cell of row transfection, cell dia are 13.8 μm, and gain media green fluorescent protein molecule is had with cell
Machine integration.When system works, the wavelength of capture light beam 17 uses 980nm, and excitation 18 wavelength of light beam uses 480nm, two-beam point
It is not passed through in two coaxial Crossed Circle core 9-1 and 9-2 and middle fiber core 9-3 of coaxial three core fibre 9 of Crossed Circle.980nm capture
Two toroidal cores light beams that light is passed through realize light reflection in centrum rotary table, are converged to ligh trap at from fiber end face a distance,
Cell posture is adjusted to precisely manipulation is carried out again with the cell of capture by adjusting the light intensity in toroidal cores respectively.Middle fiber core 9-
3 are passed through the excitation light 18 of 480nm, when the micro- ellipsoid 16 of gain substance in cell 15 and centre fibre are satisfied in the position that cell is adjusted
When the concussion condition of the issued exciting light of core waveguide 9-3, gain media is excited generated laser signal through microsphere resonator
Constantly amplification, when gain is greater than intracavitary total losses, to form laser output, laser signal 19 passes through where excitation light beam
Middle fiber core 9-3 return is received, then is transmitted to circulator 5, completes feedback path finally by spectrometer 7, is obtained cell and is swashed
Light spectrogram.
Claims (7)
1. a kind of three core fibre cell Optical Maser System of coaxial Crossed Circle with stretch function, should " optical fiber-cell " laser
Mainly be made of following four part: (1) have new structural coaxial three core fibre of Crossed Circle, the optical fiber end by rubbing down at
The cone truncated cone-shaped of rotational symmetry, is prepared into optical fiber optical tweezers；(2) miniature optical resonant cavity, it is intracavitary with optical amplifier function
Gain media can be distributed in ball, ball is outer or spherical shell surface layer；It (3) include that can provide the photodynamic light source of cell capture and increasing
Beneficial medium excitation light source；(4) the detecting light spectrum instrument of cell output laser.
2. the coaxial Crossed Circle three core fibre cell Optical Maser System according to claim 1 with stretch function, described
In Optical Maser System: capture light beam is drawn by standard single-mode fiber 6 from capture light source 2, is divided via 1 × 2 coupler 3 for two-way
Light, respectively by respectively enteing coaxial three optical fiber 9 of Crossed Circle core again after 4-2 and 4-3 attenuator and multi-core optical fiber splitter 8
In two of them annular fibre core 9-1 and 9-2.Excitation light beam is drawn by standard single-mode fiber 6 from excitation light source 1, by attenuator
4-1 and circulator 5 enter multi-core optical fiber splitter 8, subsequently into the middle fiber core 9-3 of coaxial three core fibre 9 of Crossed Circle.Sample
Liquid containing cell is filled in product pond and is stablized on objective table 11, in the sample cell that optical fiber optical tweezers 10 are immersed in, for realizing
Coaxial three core fibre probe of Crossed Circle passes through image enhancement system 12 to cell capture and manipulation, accurate displacement operation process,
The image-forming module that imaging system (CCD) 13 and computer 14 form carries out real time imagery.At the same time, the cell laser detected
Signal enters spectrometer 7 by three end circulators 5 and receives.Cell in liquid passes through by with rotational symmetry cone truncated cone-shaped
Optical fiber end optical fiber optical tweezers 10 capture, and combine manipulation, realization pair by the force trapping of cone the toroidal cores 9-1 and 9-2 of optical fiber optical tweezers
The adjustment of cell position and the stretching of posture, so that exciting light and resonance microballoon that middle fiber core 9-3 is emitted are completed accurately
Docking meets and provides excitation light source to microsphere resonator and export the condition of resonance enhancing fluorescence signal to be detected, thus from
It is assembled into novel " optical fiber-cell " laser.In the system structure of above-mentioned " optical fiber-cell " laser, wherein
Two cone annulus waveguides are played the role of carrying out the capture of light power and stretching to cell, and middle fiber core waveguide is to captured
Cell provides an exciting light, and the exciting light of sending is coupled with the microballoon after intracellular be stretched, to realize pair
The resonant excitation of microballoon and the output of laser signal, complete to the sensings of the parameters such as cell interior cytosol refractive index minor change with
Measurement.
3. the coaxial Crossed Circle three core fibre cell laser according to claim 2 with stretch function.Institute in system
The one kind being related to has three core fibre of annular coaxial Crossed Circle, it is characterized in that: the optical fiber has an intermediate core and two same
The toroidal core structure composition of axis distribution, the distance between two toroidal cores are related with the diameter of toroidal cores.
4. the coaxial Crossed Circle three core fibre cell Optical Maser System according to claim 2 with stretch function.System
Involved in a kind of optical resonance microballoon, it is characterized in that: the geometry of the resonator be center symmetric body, have elasticity,
Stress is easily-deformable, and certain gain media is contained in inside.Micro- shape resonator shape is preferential selection with microspheroidal.
5. the coaxial Crossed Circle three core fibre cell Optical Maser System according to claim 2 with stretch function.System
Involved in microballoon can be certain unicellular spherical shape, intracellular existing certain biomone or the intracellular rule of merging
Elastic ball particle.
6. the coaxial Crossed Circle three core fibre cell Optical Maser System according to claim 2 with stretch function.System
In two focuses being formed of involved two toroidal cores form two ligh traps, microballoon stress is stretched, and becomes elliposoidal from spherical shape.
7. a kind of novel " optical fiber-cell " laser self-assembling method, it is characterized in that:
(1) static capture is carried out to cell using two cone annulus waveguides；
(2) the light force trapping that microballoon is issued by two toroidal cores stretches, and keeps equilibrium state, is deformed into ellipsoid from spherical shape
Shape forms a Fabry-Perot micro chamber.
(3) microballoon is accurately coupled with the exciting light that middle fiber core waveguide issues, according to Fabry-Perot micro chamber principle, realization pair
The resonant excitation of microballoon and the output of laser signal.
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