CN109870431A - Multi-core optical fiber cell sensor with cone rotary table fibre end structure - Google Patents
Multi-core optical fiber cell sensor with cone rotary table fibre end structure Download PDFInfo
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Abstract
The present invention is to provide a kind of multi-core optical fiber cell sensor systems with cone rotary table fibre end structure.It is somebody's turn to do " optical fiber-cell " sensing system to be mainly made of following three parts: (1) there is new structural multi-core optical fiber, which, at the cone truncated cone-shaped of rotational symmetry, is prepared into optical tweezer by rubbing down；(2) microspheroidal optical resonator, the intracavitary gain media with enlarging function can be distributed in ball, outside ball or spherical shell surface layer, which, which can be, is also possible to be phagocytized by cells by the oil droplet of injection cell internal microballoon；(3) Living single cell to be measured being placed in liquid.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 cell liquid is faint, can obtain measurement by magnification by the laser output signal of multicore tapered optical fiber.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 multi-core optical fiber cell sensors with cone rotary table fibre end structure, can be used for slender
Born of the same parents' capture, the measurement of cell laser spectrum, belong to 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 sensor 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
Microcobjective focusing makes hot spot be contracted to individual cells size, and bonds out a space slightly larger than thin using two panels high reflection mirror
The Fabry-Perot cavity of born of the same parents' size, to limit cell in the position of excitation light, so the device volume is huge, it is empty
Between excitation light direction and position be not easy to adjust to unicellular, can only be captured by the method that free surrounding space limits thin
Born of the same parents.2015, the Humar et al. of medical college, Harvard University had developed a plurality of cell lasers based on Whispering-gallery-mode microcavity
(NATURE PHOTONICS, Intracellular microlasers, 2015,9:572-576), it was demonstrated that natural thin
It is intracellular to realize that laser exports, it is artificially placed in a regular circle shapes fat drips in the cell as Whispering-gallery-mode, output letter
Number it is coupled to spectral detector through 200 μm of core diameter of multimode fibre, but the device volume is larger, and receives used in signal
Optical fiber is thicker, does not also have and precisely captures to cell and micro- manipulation functions such as regulating cell ambient temperature, so that excitation beam shines
The inaccurate of cell this operation change is penetrated, the micro-displacement of cell in a liquid will lead to excitation light beam and can not accurately couple
Entering fat drop, enhance gain signal can not continuously, while also increasing the operation difficulty of experiment.
The patent of invention of Patent No. CN201510295509.8 proposes a kind of tunable liquid microsphere laser device, the patent
It is middle that two optical fiber optical tweezers is needed to carry out capture operation to microballoon 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 in the patent that optical coupling will be inputted in such a way that single mode optical fiber and annular core fibre hot melt draw cone
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, but apparatus structure and light
Fine type and central core function are had nothing in common with each other, and the present invention not only enriches the structure of optical fiber, also increase a variety of new of optical fiber
Type function, while the processing structure of optical fiber optical tweezers optical fiber end is optimized again, and then optimizes the capture light field to cell, with side throwing
The method of coupling is compared, and the coupled modes of incident light and fibre core are improved, and keeps the operability of experiment stronger.It is special with the above invention
Benefit is compared, the multicore fiber cell sensor proposed by the present invention with cone rotary table fibre end structure, the new structure of optical fiber
Multiple fibre cores including three or three or more different distributions, by the temperature of cell capture, cell posture micro-control, cell peripheral
Multiple functions such as regulation, the excitation of gain substance and optical signal reception are integrated in the same optical fiber, and optimize optical fiber optical tweezers
To the capture light field of cell, the invention is by the analysis and detection to Living single cell and to the essence and rule for disclosing vital movement
Rule, provides more reliable scientific basis.
The present invention proposes a kind of multi-core optical fiber cell sensing with cone rotary table fibre end structure under background above
Device.On the one hand the optical band that it can be different by the beam Propagation in different fibre cores, 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, middle fiber core can pass
Defeated capture laser completes cell in the micro-displacement of radial position, and tool carries out high-precision posture and situation monitoring to cell, makes
Excitation light path is accurately docked with the completion of resonance microballoon, in addition, in order to realize the stable operation of system, which is also equipped with
It is able to carry out the monitoring to cell peripheral environment temperature and adjusting function.This device uses novel multi-core optical fiber, has multi-pass
The characteristics of Highgrade integration, volume and flexible flexible nature with very little are the life science problem of Living single cell
Exploration and research provide important multi-purpose tool, the present invention is a kind of novel biography under subject crossing fusion development trend
Sensor, therefore have a very important significance and be worth.
(3) summary of the invention
The purpose of the present invention is to provide a kind of multi-core optical fiber cell sensors with cone rotary table fibre end structure, can use
In unicellular capture, the measurement of cell laser spectrum.
The object of the present invention is achieved like this:
Multi-core optical fiber cell sensor with cone rotary table fibre end structure, should " optical fiber-cell " sensor mainly by
Three parts form below: (1) having new structural multi-core optical fiber, the optical fiber end is by rubbing down at the cone rotary table of rotational symmetry
Shape is prepared into optical tweezer；(2) microspheroidal optical resonator, the intracavitary gain media with enlarging function, can be distributed in ball,
Ball is outer or spherical shell surface layer, the microballoon can be the microballoon for being also possible to be phagocytized by cells inside by the oil droplet of injection cell；
(3) Living single cell to be measured being placed in liquid.In the system: capture light beam by standard single-mode fiber 17 from capture light source 2
It draws, divides via 1 × N coupler 5 for multichannel light, by entering back into multi-core optical fiber after attenuator 4 and multi-core optical fiber splitter 8
In 9 capturing function fibre core.Wherein there is a-road-through overdamping device 4-5 to enter in WDM7 together with temperature control light beam, enters back into multicore
In the middle fiber core of optical fiber splitter 8 and multi-core optical fiber 9.Excitation light beam is drawn by standard single-mode fiber 17 from excitation light source 1, is passed through
Overdamping device 4 enters multi-core optical fiber splitter 8, swashs subsequently into the cell in the arousal function fibre core of multi-core optical fiber 9, detected
Optical signal enters spectrometer 15 by three end circulator 6-1 and receives.Temperature control light beam is drawn by standard single-mode fiber 17 from temperature control light source 3
Out, multi-core optical fiber splitter 8 is entered back by circulator 6-2 and WDM7, finally entered in the middle fiber core of multi-core optical fiber, detected
To cell peripheral temperature environment feedback signal by three end circulator 6-2 enter spectrometer 16 receive.
Cell aqueous solution is filled in sample cell and is stablized on objective table 11, in the sample cell that optical fiber optical tweezers 10 are immersed in, is used
In realizing capture and manipulation of the multi-core optical fiber probe to cell, accurate displacement operation process by microcobjective 12, CCD13 and
The image-forming module that computer 14 forms carries out real time imagery.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 capture fibre core of optical fiber optical tweezers and the force trapping of middle fiber core
The posture of cell and position are accurately adjusted, so that exciting light and resonance cell that excitation fibre core 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 " sensor.In the system structure of above-mentioned " optical fiber-cell " sensor, liquid
In living body cell to be measured by being captured by the optical fiber end optical tweezer with cone truncated cone-shaped, by the force trapping of optical fiber optical tweezers and in
Between fiber cores light radiation thrust joint manipulation, realization the posture of cell and position are accurately adjusted so that excite
The exciting light that function fibre core is emitted and the laser by the output of microspheroidal resonant cavity meet coupling condition just.First fibre core
Waveguide series plays the role of carrying out cell the capture of light power, and intermediate core waveguide provides one to captured cell
The effect of light radiation thrust, by the light hydrodynamic regulation of these power, so that intracellular microballoon and second core waveguide system
Column realize accurately coupling, to realize to the resonant excitation of cell and the output of laser signal, as shown in Figure 1.
Multi-core optical fiber 8 of the present invention can be a kind of three core fibres or five core fibres with linear distribution,
As shown in Fig. 2 (a)-(b), it is also possible to a kind of five core fibres with cross distribution, seven core fibres or nine core fibres, such as schemes
Shown in 2 (c)-(e), it can also be a kind of nine core fibres with square lattice distribution, as shown in Fig. 2 (f).It is one of fine
Core waveguide series is used for transmission capture light beam, another core waveguide series is in transmission excitation beam, to realize to microballoon
Resonant excitation exports collected laser signal again to spectrometer, and intermediate core channel is then thin for assisting precisely to manipulate
Born of the same parents' pose adjustment, while also having the function of being able to carry out monitoring and regulation to cell peripheral environment temperature, in each fibre core
The possibility of light classification is passed through as shown in fibre core in Fig. 2.
Light beam is captured to inject in the capture fibre core of multi-core optical fiber 9 by coupler 5 and attenuator 4.The wave band light beam is used for
The capture of cell, method are to have the reflection frustum multi-core optical fiber end structure of rotational symmetry as made of fine gtinding as optical fiber
Optical tweezer 10, the refraction for transmitting beam in fibre core are assembled, and are formed light and are captured potential well.It is transmitted in the capture fibre core of multi-core optical fiber
Capture light beam can carry out reflection focusing by the frustum cone structure, to realize deeper capture potential well, be used for cell capture.For
It realizes and capture and excitation is stablized to cell, optical fiber optical tweezers can be prepared by optical fiber end rubbing down technology, such as rotational symmetry
Cone frustum cone structure, as shown in Figure 5.
In order to meet refraction convergence, frustum base angle needs to meet: α < arcsin (n1/n2), n1For liquid environment locating for cell
Refractive index, n2For toroidal cores refractive index.In order to reduce optical power and improve light power to the precision of the cell of capture manipulation, need
Keep light field smaller in the three dimension scale of dimensional energy focus point, improves tapered optical fiber end to light field focus characteristics, so that optical fiber end
Intersection light field convergence focal spot it is smaller, for this purpose, can be realized by optimizing the method for the cone frustum cone structure of rotational symmetry.
Radian cone frustum cone structure (Fig. 3 (b)) is processed into section cone frustum cone structure (Fig. 3 (a)), is optimized by the arc of section,
The waist spot scale of fibre core outgoing beam can be further compressed, so that energy be made more to concentrate, this can enhance force trapping, and
Total optical power can preferably be reduced.The method calculated using numerical simulation, compares two kinds of typical optical fiber ends in arc
It is preceding and excellent to compare roughly optimization in the case where the total optical power of input is constant for the optical field distribution strength conditions for optimizing front and back
After change at 1/e field strength hot spot width, the results showed that, the former is the latter more than 2 times, as shown in Figure 4.
The optical gradient forces potential well issued using the optical fiber optical tweezers (shown in Fig. 5) of the radian cone frustum cone structure after optimization
During capturing cell, each waveguide can regulate and control light intensity by attenuator independent, can not only capture cell,
And can be realized the whole manipulation of cell position (X, Y, Z), the process of this manipulation can be seen by microscopical ccd image
It surveys to feed back its adjustment effect roughly, to further change the optical power size of each light beam.With five core fibre of linear distribution
For, the stress condition of captured cell is as shown in fig. 6, the focus of the capture light beam in capture fibre core corresponds to gradient force gesture
The bottom of trap only provides a radiation thrust F by middle fiber core to realize in Z-direction compared with change in displacement0, thus with
Capture the F that fibre core issues1-F4It mutually balances to complete the capture of cell.
Middle fiber core is passed through two kinds of light beams of capture light source and temperature control light source by WDM7, in addition to providing cell pose adjustment
Power light source outside, and increase a function to ambient temperature measurement and monitoring.After cell is captured by optical fiber optical tweezers,
The intensity of the capture light beam issued in capture fibre core and middle fiber core is adjusted by attenuator 4, thus it is possible to vary optical gradient forces
The distribution of potential well, to make cell that can radially obtain a small-scale displacement change.In order to realize that middle fiber core can
Measurement and monitoring system environment temperature, middle fiber core will be written into the fiber grating (as shown in Figure 7) of 1550nm wave band, a side
Face can be realized the ambient temperature measurement of sensing system by means of the response characteristic of this fiber grating pair temperature；Another party
It face can be in cell external environment temperature due to using the light (aqueous solution absorption coefficient is larger) of 1550nm infrared band
In the case that degree reduces, by providing light energy come the liquid (photo-thermal effect) around heating cells, to reach promotion cell
The method of environment temperature realizes the regulation of sensor microsystems environment temperature, this open system is made to be in the perseverance of dynamic equilibrium
Temperature state is in sensor under stable temperature constant state and works to keep the stabilization of system ambient temperature.There is also the need to
Consider the problems of exist including the emergent light of weaker 1550nm wave band is able to maintain that cell peripheral liquid is in one dynamically
Equilibrium temperature is also smaller to the active force of the cell in dynamic force balanced state since optical power is smaller；When needing light
When thermal power is larger, can mechanical balance state to cell have an impact, can make by adjusting the method for capture light beam power
It realizes rebalancing.
In order to form " optical fiber-cell " sensor, need to carry out active somatic cell to be measured microballoon insertion pretreatment, so as to
Cell interior building has the microspheroidal optical resonator of signal gain.There are two types of the embedding grammar of intracellular microballoon is general: one
Kind is that fluid oil is instilled into cell interior by way of injection, has stronger surface tension using liquid, can be with shape
At smooth boundary, natural optical microcavity is generated, for example, Humar et al. extracts fat from fresh porcine skin tissue, gain is situated between
Matter is Nile red dye, and being uniformly mixed into refractive index with polyphenyl ether oil is 1.69, nontoxic low-viscosity liquid of the diameter at 4~20 μm
Drop, it is intracellular to be injected into HeLa using microinjector；Another kind is to use the microballoon of polymerizable material as resonant cavity, benefit
Make microballoon enter cell interior with endocytosis to form microcavity, reach for example, HeLa and NIH3T3 cell can swallow diameter
20 μm of microballoon.
Light beam is motivated to inject the excitation fibre core of multi-core optical fiber 9 by attenuator 4, circulator 6-1 and multi-core optical fiber splitter 8
It is interior.The excitation beam transmitted in excitation fibre core can carry out reflection focusing by the frustum cone structure, the light beam of focusing have compared with
Strong energy density is able to achieve the excitation of captured cell laser, method are as follows: cell be captured fibre core sending beam-capturing
It after firmly, is excited by excitation light, microballoon intracellular at this time can be used as an optics Echo Wall microcavity, the laser signal after excitation
It is limited in the resonant cavity of micro-nano magnitude, it is understood that be the light of round-trip transmission in Fabry-Perot-type cavity along circular rail
Mark moves ahead around chamber, and Whispering-gallery-mode light should meet two primary conditions and can realize stable transmission intracavitary, one of them is
Total internal reflection condition, when angle of incidence of light is greater than a certain critical angle, according to refractive index leaded light principle, light can be limited in
Transmission in high refractive index medium, without reflecting；Another condition is phase-matching condition, and the calculation formula of resonance wavelength is
The π of λ=2 Rneff/ m, R are the radius of microballoon microcavity, neffFor the effective refractive index of microsphere medium, m is integer.Fig. 8 is that the Echo Wall 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 present invention at least has obvious advantage below:
(1) a kind of cell sensor is proposed.Other slender cytoplasm sensors having proposed are compared to, it is proposed by the present invention
Sensor have the characteristics that it is noninvasive, real time laser spectral detection may be implemented.
(2) unicellular capture technique and cell sensor are integrated in same root multi-core optical fiber by the present invention, can be provided
Eucaryotic cell structure and chemical composition information abundant.Therefore the present invention can realize single celled analysis comprehensive, multi-functionally.
(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 multi-core optical fiber cell sensor system of cone rotary table fibre end structure: (a) device
In capture systems and excitation system；(b) temperature-controlling system in device.
Fig. 2 is new construction multi-core optical fiber schematic diagram, and (a) is that three core fibres (b) of linear distribution are five cores of linear distribution
It is seven core fibres (e) of cross distribution is nine core fibres (f) of cross distribution that optical fiber, which is (c) five core fibres (d) of cross distribution,
It is square the classification of be passed through light in nine core fibres and each core waveguide of grid distribution.
Fig. 3 is optical fiber cone rotary table arc prioritization scheme: optical fiber cone rotary table before (a) optimizing；(b) optical fiber cone after optimizing
Rotary table.
Fig. 4 is to have carried out quantization for the focal beam spot of fine end structure arc optimization both front and back situation to compare figure, the former
Compared with the latter, spot diameter is smaller, and energy density is higher.
Fig. 5 is the arc-shaped cone frustum cone structure schematic diagram of rotational symmetry at five core fibre ends of collinearity distribution.
Fig. 6 is that five core fibres of linear distribution bring out the multiple beam combination light field schematic diagram penetrated.
Fig. 7 is the fiber grating temperature monitoring sensor schematic positioned at fine end.
Fig. 8 is Echo Wall resonant cavity microballoon operation principle schematic diagram.
Fig. 9 is that there is the intact device of the five core fibre cell sensor system of linear distribution of cone rotary table fibre end structure to show
It is intended to.
Figure 10 is the nine core fibre cell sensor systems pair with the square lattice distribution of cone rotary table fibre end structure
Cell captured, temperature control, excitation and detection operation schematic diagram.
(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.
Below by taking the cell sensor system of multi-core optical fiber as an example, the present invention is specifically described.
Embodiment 1: laser measurement of the cell sensor of five core fibres based on linear distribution to monomer living cells.
Fig. 9 is the intact device schematic diagram with the multi-core optical fiber cell sensor system of cone rotary table fibre end structure, it
By excitation light source 1, light source 2, temperature control light source 3, attenuator 4, coupler 5, circulator 6, wavelength division multiplexer (WDM) 7, multicore are captured
Optical fiber splitter 8, five core fibres 9, optical fiber optical tweezers 10, objective table 11, microcobjective 12, CCD13, computer 14 and 350nm~
1750nm spectrometer 15 and 16 and standard single-mode fiber 17 form.In the system: capture light beam is by standard single-mode fiber 17
Draw from capture light source 2, divide via 1 × N coupler 5 for multichannel light, by after attenuator 4 and multi-core optical fiber splitter 8 again
Into in the capturing function fibre core of multi-core optical fiber 9.Wherein there is a-road-through overdamping device 4-5 to enter WDM7 together with temperature control light beam
In, it enters back into the middle fiber core of multi-core optical fiber splitter 8 and multi-core optical fiber 9.Motivate light beam by standard single-mode fiber 17 from swash
The extraction of light source 1 is encouraged, enters multi-core optical fiber splitter 8 by attenuator 4, subsequently into the arousal function fibre core of multi-core optical fiber 9,
The cell laser signal detected enters spectrometer 15 by three end circulator 6-1 and receives.Temperature control light beam is by standard single-mode fiber
17 draw from temperature control light source 3, enter back into multi-core optical fiber splitter 8 by circulator 6-2 and WDM7, finally enter multi-core optical fiber
In middle fiber core, the feedback signal of the cell peripheral temperature environment detected enters spectrometer 16 by three end circulator 6-2 and connects
It receives.Cell aqueous solution is filled in sample cell and is stablized on objective table 11, in the sample cell that optical fiber optical tweezers 10 are immersed in, for realizing
Capture and manipulation of the multi-core optical fiber probe to cell, accurate displacement operation process pass through microcobjective 12, CCD13 and computer
The image-forming module of 14 compositions carries out real time imagery, as shown in Figure 9.
Here cell selects HEK293 human embryonic kidney cells 18, and this cell is the food in one's mouth for being commonly used to be transfected in biology
Newborn zooblast, cell dia are 13.8 μm, and gain media green fluorescent protein molecule and cell are carried out organic combination.System
When work, the wavelength of capture light beam 20 uses 980nm, and excitation 21 wavelength of light beam uses 480nm, and two kinds of light each lead into multi-core optical
In the capture fibre core series and excitation fibre core series of fibre 9.Two wave band light beams being passed through realize light reflection in cone rotary table, and
Ligh trap is pooled at from fiber end face a distance.Middle fiber core is equally passed through the capture light 20 of 980nm, to the thin of capture
Born of the same parents carry out precisely manipulating adjustment cell posture again, while being also passed into the wide range temperature control light 22 that central wavelength is 1550nm, to cell
Ambient temperature is monitored and is regulated and controled in real time.When gain substance microballoon in cell 18 is satisfied in the position that cell is adjusted
19 with the coupling condition of the issued exciting light of excitation core waveguide series when, the gain media generated laser signal that is excited passes through
Microsphere resonator constantly amplifies, and when gain is greater than intracavitary total losses, to form laser output, laser signal 23 is by swashing
It encourages to return in the fibre core where light beam and be received, then be transmitted to circulator 6-1, complete feedback path finally by spectrometer 15,
Obtain cell laser light spectrogram.
Embodiment 2: Laser Measuring of the cell sensor of nine core fibres based on square lattice distribution to monomer living cells
Amount.
The system is identical as the cell sensor device composition of five core fibre of linear distribution, due to the quantity and distribution of fibre core
It changes, the capture light beam 20 and excitation beam 21 in system enter multi-core optical fiber splitter 8 by 1 × 4 coupler 5 respectively
In, it is injected into corresponding fibre core respectively, wherein fibre core a b c d i is capturing function fibre core, and what is injected is capture
Light beam 20, fibre core e f g h are arousal function fibre core, and what is injected is excitation beam 21, and middle fiber core e is also equipped with temperature here
The function of monitoring, so again by injection temperature control light beam 22.
Here cell selects HEK293 human embryonic kidney cells 18, and when system works, the wavelength of capture light beam 20 is used
980nm, excitation 21 wavelength of light beam use 480nm, and middle fiber core carries out the cell captured precisely to manipulate adjustment cell appearance again
State, while also cell peripheral environment temperature is monitored and regulated and controled in real time.Intracellular laser signal 23 passes through excitation light
It returns and is received in fibre core where beam, then be transmitted to circulator 6-1, complete feedback path finally by spectrometer 15, obtain
Cell laser light spectrogram, as shown in Figure 10.
Claims (6)
1. with cone rotary table fibre end structure multi-core optical fiber cell sensor, should " optical fiber-cell " sensor mainly by with
Lower three parts form: (1) having new structural multi-core optical fiber, the optical fiber end is by rubbing down at the cone rotary table of rotational symmetry
Shape is prepared into optical tweezer；(2) microspheroidal optical resonator, the intracavitary gain media with enlarging function, can be distributed in ball,
Ball is outer or spherical shell surface layer, the microballoon can be the microballoon for being also possible to be phagocytized by cells inside by the oil droplet of injection cell；
(3) Living single cell to be measured being placed in liquid.In the sensor-based system: capture light beam by standard single-mode fiber 17 from capture light
Source 2 is drawn, and is divided via 1 × N coupler 5 for multichannel light, respectively by distinguishing again after attenuator 4 and multi-core optical fiber splitter 8
Into in the capturing function fibre core of multi-core optical fiber 9.Excitation light beam is drawn by standard single-mode fiber 17 from excitation light source 1, by declining
Subtract device 4 and enter multi-core optical fiber splitter 8, subsequently into the arousal function fibre core of multi-core optical fiber 9.Cellular water is filled in sample cell
Solution is simultaneously stablized on objective table 11, in the sample cell that optical fiber optical tweezers 10 are immersed in, for realizing multi-core optical fiber probe to cell
Capture and manipulation, accurate displacement operation process are carried out by the image-forming module that microcobjective 12, CCD13 and computer 14 form
Real time imagery.At the same time, the cell laser signal detected enters spectrometer 15 by three end circulator 6-1 and receives.Liquid
In cell by being captured by the optical fiber optical tweezers 10 with rotational symmetry cone truncated cone-shaped, captured by the cones of optical fiber optical tweezers fine
The force trapping of core combines manipulation, and realization accurately adjusts the posture of cell and position, so that excitation fibre core was emitted
Exciting light is accurately docked with the completion of resonance microballoon, is met and is provided excitation light source to microsphere resonator and export resonance to be detected
The condition for enhancing fluorescence signal, to be self-assembled into as novel " optical fiber-cell " sensor." optical fiber-is thin above-mentioned
In the system structure of born of the same parents " sensor, wherein a series of core waveguides play the role of carrying out the capture of light power to cell, and it is intermediate
Core waveguide provides the effect of a light radiation thrust to captured cell, by multiple smooth hydrodynamic regulations, so that cell
With the exciting light that another serial core waveguide issues can be realized it is accurate couple, to realize the resonant excitation to cell and swash
Sensing and measurement to parameters such as cell interior cytosol refractive index minor changes are completed in the output of optical signal.
2. a kind of temperature-controlling system applied to the multi-core optical fiber cell sensor with cone rotary table fibre end structure, the system have
Monitoring and adjusting function to the cell peripheral environment temperature captured, make system be in the temperature constant state of dynamic equilibrium, thus
The stabilization of system ambient temperature is kept, to achieve the purpose that the viability environment constant temperature to cell maintains.Temperature control light beam is by standard list
Mode fiber 17 is drawn from temperature control light source 3, is entered multi-core optical fiber splitter 8 by circulator 6-2, is finally entered corresponding multi-core optical fiber
Middle fiber core in, the feedback signal of the cell peripheral temperature environment detected enters spectrometer 16 by three end circulator 6-2
It receives.
3. the multi-core optical fiber cell sensor according to claim 1 with cone rotary table fibre end structure.It is involved in system
And multi-core optical fiber can also it is characterized in that: the optical fiber can be a kind of three core fibres or five core fibres with linear distribution
To be a kind of five core fibres with crossing distribution, seven core fibres or nine core fibres, more can be a kind of has square
Nine core fibres of grid distribution.
4. the multi-core optical fiber cell sensor according to claim 1 with cone rotary table fibre end structure.It is involved in system
And a kind of optical resonance microballoon, it is characterized in that: the microballoon is that single rule is spherical, and microballoon contains certain gain media,
Microballoon can be injected into cell interior by way of injection, microballoon can also be made to enter in such a way that cell actively swallows
Cell interior.
5. according to claim 2 a kind of applied to the multi-core optical fiber cell sensor with cone rotary table fibre end structure
Temperature-controlling system.Related temperature-controlling system, it is characterized in that: in the middle fiber core of multi-core optical fiber, nearly 10 end of optical fiber optical tweezers write-in one
The fiber grating of a 1550nm wave band realizes the ambient temperature measurement of system by the response characteristic of fiber grating pair temperature, again
Because aqueous solution is larger to the absorption coefficient of light of 1550nm infrared band, so as to promote cell peripheral environment temperature, thus
Realize regulation of the heating system of sensor to temperature.
6. a kind of method that multi-core optical fiber and cell are combined into " optical fiber-cell " sensor.Living body cell to be measured in liquid is logical
It crosses by the optical fiber end optical tweezer capture with cone truncated cone-shaped, is pushed away by the light radiation of the force trapping and intermediate fibres core of optical fiber optical tweezers
The joint of power manipulates, and realization accurately adjusts the posture of cell and position so that arousal function fibre core emitted it is sharp
It shines and the laser by the output of microspheroidal resonant cavity meets coupling condition just, to be self-assembled into as a novel " light
Fibre-cell " sensor.In the system structure of above-mentioned " optical fiber-cell " sensor, first core waveguide series is played to thin
Born of the same parents carry out the effect of light power capture, and intermediate core waveguide provides the work of a light radiation thrust to captured cell
With by the light hydrodynamic regulation of these power, so that intracellular microballoon and second core waveguide series realize accurate coupling
It closes, to realize to the resonant excitation of cell and the output of laser signal.
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| CN110993141A (en) * | 2019-11-15 | 2020-04-10 | 桂林电子科技大学 | Multi-core optical fiber suspension type optical motor system |
| CN111117860A (en) * | 2019-11-04 | 2020-05-08 | 桂林电子科技大学 | Cell micro-scalpel based on optical fiber glimmer hand and preparation method thereof |
| CN113219581A (en) * | 2020-11-24 | 2021-08-06 | 桂林电子科技大学 | Single-fiber-core beak-shaped optical fiber tweezers with sorting function and preparation method thereof |
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Application publication date: 20190611 |