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FI.DESCRIPTIONTITLE OF INVENTIONA multi-core optical fiber cellular laser system with stretching function
TECHNICAL FIELD[0001] The present invention relates to a multi-core optical fiber cellular laser system with
stretching function, which can be used for cells trapping, cells laser spectrum measurement and
self-assembly of cellular lasers, particularly suitable for the technical field of single cell
manipulation, measurement and analysis.
BACKGROUND ART[0002] In 1960, physicist T.H. Maiman and others successfully created the world's first ruby
crystal laser. In 1961, A. Jia Wen and others successfully developed a helium-neon laser, and in
1962, R.N. Hall and others developed gallium arsenide semiconductor laser. The birth of the
laser marks people's ability to regulate the emission direction, phase, frequency, and polarization
of multiple photons, so that people's understanding and application of light have reached a higher
level. Lasers show unprecedented application value in the direction of miniaturization and
interdisciplinary, so the field of optical fluid lasers came into being. Optical fluid is a new
multidisciplinary research field formed by combining the unique advantages of optics and fluids.
The concept was proposed by the California Institute of Technology in 2003. The biological
body has a natural liquid environment. Sensory detection and imaging have very broad application prospects.
[0003] The cellular laser is a special optofluidic laser (Research Progress and Application of
Cellular lasers. Article in Laser & Optoelectronics Progress 55(12):120001), which can simulate
the liquid environment in which organisms live in vitro or directly in vivo , and under the
excitation of external energy to achieve the laser output of the cell. Compared with the current
fluorescent signal detection methods commonly used in various fields of biomedicine, the use of
laser signal detection has its own unique advantages. First, the laser signal is the spontaneous
radiation of stimulated radiation different from the fluorescent signal. The signal of the resonant
cavity will have good directivity after amplification and feedback; secondly, when the excitation
source laser signal is higher than the threshold, the signal energy output by the working particles
is much higher than the fluorescence signal, so the resolution and sensitivity of the laser signal
detection will also be higher than fluorescence detection, and the line width of the laser signal
output spectrum is extremely narrow compared with the fluorescence spectrum of the
luminescent material, which is conducive to timely response during the sample detection
process. The gain media commonly used in cellular lasers are generally fluorescent materials,
such as fluorescent proteins (Gather, M. C., & Yun, S. H. (2011). Single cell biological lasers.
Nature Photonics, 5(7), 406-410), fluorescent dyes (X. Zhang, et.al. Bio-switchable optofluidic
lasers based on DNA Holliday junctions. Lab on a Chip, 01 Oct 2012, 12(19):3673-3675),
fluorescein, quantum dots, vitamins, and fluorescence energy resonance transfer, etc., organically
integrate the gain medium with the cell, and the gain signal emitted after absorbing excitation
energy is continuously oscillated and feedback amplified by the optical resonant cavity, when the
gain is greater than the total loss in the cavity, a laser output is formed.
[0004] In June, 2001, Gather et.al. of Harvard University allowed human fetal kidney cells to
emit laser signals (Gather, M. C., & Yun, S. H. (2011). Single cell biological lasers. Nature
Photonics, 5(7), 406-410). The excitation light of the device need to pass the focus of the
imaging amplifying systems which reduces the light spot to the size of a single cell, and uses two
high-reflection mirrors to bond a Fabry-Perot cavity with a space slightly larger than the cell size to limit the cells in the position of the excitation light. The device is bulky, and the direction and position of the spatial excitation light are not easy to adjust for single cells, and the cells can only be trapped by means of external space limitations. In 2015, Humar et.al. of Harvard Medical School developed a variety of cellular lasers based on whispering-wall mode microcavities (Humar, M.; Yun, S. H. Intracellular microlasers, Nature Photonics, 2015, 9:572-576), which proved to be achievable in natural cells. Laser output, which artificially inserts a regular circular lipid droplet into the cell as the echo wall mode. The output signal is coupled to the spectral detector through a multimode fiber with a core diameter of 200m, but the device is large and the fiber used to receive the signal is thicker and since it does not have micro-operational functions such as precisely trapping the cells, which makes the operation of the excitation beam irradiating the cells less precise. The slight displacement of the cells in the liquid will cause the excitation beam to not be accurately coupled into the fat drops, which makes the gain signal unable to be continuously enhanced, and also increases the difficulty of the experiment.
[0005] Regarding the trapping and stretching of cells due to optically induced surface forces, common approaches to cell stretching are that individual suspended cells can be deformed by optically induced surface forces through optical stretchers combined with microfluidic delivery, through two beams of spatial light oriented in opposite directions so that cells within the microfluidic channels can be trapped and deformed by the divergent laser beam (Guck, J., et.al. The optical stretcher: a novel laser tool to micromanipulate cells, Biophysical Journal, 2011, 81:767-784). Other methods include, through the connection of red blood cells to two protein coated silicon dioxide pellets, one of the pellets is fixed to a glass plate and the other pellet is trapped by the optical tweezers, where the pellet moves with the movement of the optical tweezers during the movement of the optical trap, and this achieves the effect of stretching the red blood cells (Lim. C. T., et.al., Large deformation of living cells using laser traps, Acta Materialia, 2004, V52, 7:1837-1845). In addition, there are also direct adhesions to cells using glass or metal tips, and the viscosity of the cells is measured by the stretching and bending of the distance between the two tips, this can also stretch the cells. (Desprat, N.., et.al., Creep Function of a Single Living Cell, Biophysical Journal, 2005, 88: 2224-2233). These methods all contain devices in two opposing directions, including optically powered and mechanically powered, to perform contact or non-contact stretching operations on both sides of the cells, in which due to light sources and other reasons, other devices such as microfluidic channels will also be required to ensure that the stretched cells can always be in an easy-to-survive environment, and can only be operated by passing spatial light through the microfluidic channels. The proposed cellular laser based on a new fiber structure integrates the functions of cells trapping, stretching, exciting and receiving, largely reduces the number and size of the required devices, reduces the experimental steps, and reduces the experimental difficulty.
[0006] The invention patent with patent number CN201510295509.8 proposes a tunable liquid
cellular laser. In this patent, two optical fiber tweezers are required to trap the cells at the same
time, and use the method of using one optical fiber to output and another optical fiber to receive
to collect signal lights; the invention patent with patent number CN201510267391.8 proposes a
droplet whispering wall mode laser and its fabrication method. In this patent, the input light
needs to be coupled into the ring core by means of melting tapering of the single-mode optical
fiber and the ring core fiber. The droplet also needs to contact the micro-nano fiber to transmit
the signal light. The invention patent with the patent number CN201510271055.0 proposes a
multi-wavelength droplet laser. In this patent, since multiple droplets need to be excited and
detected, the same as the previous patent, each droplet needs contact with a micro-nano fiber and
output, this method undoubtedly increases the difficulty of the device. As we all know, the size
of the micro-nano fiber is only a few microns, which is easily affected by the external
environment, and it is difficult to keep the surface of the fiber clean for a long time. The linear
arrangement of the droplets means that multiple micro-nano fibers are required for linear
distribution. Due to the small size of the droplets, this also places extremely high requirements
on the experimental operation. The invention patent with the patent number 201810169543.4
proposes a living single cell multifunctional spectrograph based on coaxial dual-waveguide
optical fiber. The cell micro-optical "hand" mentioned in this patent is similar to the principle of
optical fiber trapping cells used in this patent, also uses multiple cores to trap, but the device
structure and the function of the central core are different. The present invention not only
enriches the structure of the optical fiber, but also adds a variety of new functions of the optical
fiber, and at the same time changes the processing structure of the optical fiber end of the optical fiber tweezers, thereby changing the position of field of light for trapping of the cells, making the experiment more operable. Compared with the above invention patents, the present invention proposes a multi-core optical fiber cellular laser system with stretching function. The new structure of the optical fiber includes one central core and multiple cores of different core distributions, which can integrates multiple functions such as cells trapping, cells attitude stretching, gain medium exciting and optical signals receiving in the same optical fiber, and the optical field of optical fiber tweezers for cells is optimized. This invention will provide a more reliable scientific basis for the analysis detection of living single cells and for revealing the essential laws of life activities.
[0007] The present invention presents, in the above context, a multi-core optical fiber cellular
laser system with stretching function. On the one hand, it is capable of transmitting different
optical wavelengths through multiple cores, thus completing the trapping of cells, the
distribution of the operational optical fields and the excitation of cellular lasers, thus possessing
the characteristics of optical field control and excitation. On the other hand, through regulating
the trapped light intensity to adjust the optical trap distribution intensity, and the degrees of
stretching can be controlled so that the excitation light path can be precisely docked with the
micro resonator. The device uses a new multi-core optical fiber, it has a characteristics of highly
integrated multiple optical paths, a small size and bendable flexibility, providing an important
multifunctional tool for the exploration and study of life science problems in living single cells,
the present invention is a new type of laser under the trend of interdisciplinary fusion, so it has a
very important significance and value.
SUMMARY OF INVENTION[0008] The purpose of the present invention is to provide a multi-core optical fiber cellular laser
system with stretching function that can be used for single cell trapping and cellular laser
spectroscopy measurements.
[0009] A multi-core optical fiber cellular laser system with stretching function, the "fiber-cell" laser comprises of the following four parts: (1) A multi-core optical fiber with a new structure, where the fiber end is polished into a rotationally symmetrical dual-angle cone-frustum-shape to prepare fiber optical tweezers; (2) A micro optical resonant cavity with a gain medium for optical amplification function, can be distributed in the sphere, outside the sphere or on the surface of the sphere; (3) A light source that can provide trapping photodynamic for cells with a wavelength of 980nm, and a gain medium excitation light source with a wavelength of 460-670nm; (4) A cell output laser detection spectrograph. In the laser system: the trapping beam is extracted from the trapping light source 2 by a standard single-mode optical fiber 6, divided into N paths of light via a 1xN coupler 3, respectively passing through the attenuators 4-2 to 4-N and the multi-core optical fiber fan in/out device 8, then into any core but the central core of the multi-core optical fiber 9. The excitation light beam is extracted from the excitation light source 1 by the standard single-mode optical fiber 6, enters the multi-core optical fiber fan in/out device 8 through the attenuator 4-1 and circulator 5, and then enters the central core of the multi-core optical fiber 9.
[0010] The sample pool filled with liquid with cells is stabilized on the stage 11, and the fiber optical tweezers 10 are immersed in the sample pool, which is used to achieve the trapping and manipulation of the cell by a multi-core optical fiber probe, and the precise displacement operation process is carried out through the real-time imaging by the imaging module composed of a imaging amplifying system 12, a CCD 13 and a computer 14. At the same time, the detected cellular laser signal is received by the spectrograph 7 via a triple-end circulator 5. The cells in the liquid are trapped by the fiber optical tweezers 10 with a rotationally symmetrical cone frustum-shaped fiber end, through the joint manipulation of the trapping forces of the fiber optical tweezers, achieving position adjustment and the stretching of the attitude of the cells, making the excitation light emitted by the central core and the resonant cell precisely dock, which satisfies the conditions of providing an excitation light source to the cell resonant cavity and outputting the resonance enhanced fluorescence signal to be detected, thereby self assembling into a new type of "fiber-cell" laser. In the "fiber-cell" laser system structure, multiple waveguides play a role in the photodynamic trapping and stretching of the cells, and the central core waveguide provides an excitation light to the trapped cells. This enables emitted excitation late to couple with the stretched microspheres in the cells, thereby achieving resonant excitation of the microspheres and the output of laser signals, completing the sensing and measurement of small changes in the refractive index of the cytosol inside the cells and other parameters, as shown in FIG. 1.
[0011] The multi-core optical fiber 9 of the invention has one central core waveguide and
multiple side-core waveguides of different shapes of distributions. In which the multiple core
waveguides are used to transmit the trapped beam and precisely control and adjust the cells'
attitude the other and the central core is used to transmit the excitation beam. FIG. 2 shows the
structure and refractive index distribution of a multi-core optical fiber, as well as the type of light
passing through the waveguide in each fiber core.
[0012] The trapping beam is injected into multiple cores of the multi-core optical fiber 9 through
a coupler 3 and attenuators 4-1 to 4-N. The beam is used for the trapping of cells by using the
fiber end of the multi-core optical fiber to prepare a rotationally symmetrical reflective cone
table structure by precisely polishing. This acts as the optical fiber optical tweezers 10, for
refractive convergence of the transmitted light beam in multiple cores to form an optical trapping
force. The trapped beam transmitted within the any core but the central core of the multi-core
optical fiber can also reflect and focus via the frustum structure, achieving a deeper trapping
potential well for trapping cells. To achieve stable trapping and excitation of cells, optical fiber
optical tweezers can be fabricated by fiber end polishing techniques, such as a rotationally
symmetric multi-angle cone-frustum structure, as shown in FIG. 4. In order to satisfy the
refractive convergence, the cone base angle a should satisfy: a arcsin(n/n)whereni is the refractive index of the liquid environment in which the cell is located, n2 is the refractive index
of the core. In order to increase the distance between the focuses so that the cells can be stretched
more widely, this can be achieved by the method of optimizing the rotationally symmetrical
cone-frustum structure. Process the faceted cone-frustum structure (FIG. 3(a)) into a multi-angle
cone-frustum structure (FIG. 3(b)). Through the change of the facet structure, this can further
increase the distance between the two focal points which increases the range of manipulation of cells.
[0013] The optical gradient force of cells carried out by using the processed optical fiber optical tweezers of a multi-angle cone-frustum structure (as shown in FIG. 4), every waveguide can regulate optical intensity through its own independent attenuators. This not only traps the cells, but also is able to achieve the stretching manipulation of the cells at the Z radial direction of position (X, Y, Z). The process of this manipulation can obtain rough feedback of the effects of the adjustments by observing the microscope CCD imaging. When the position of the cell near the two focal points of the beam becomes stressed and the cell as a whole is stretched and deformed, the optical power of each beam can be further varied according to the deformation. The forces on the trapped cells are shown in FIG. 5, and the focus of the trapped beam in the core corresponds to the bottom of the gradient force. Fi to F 4 on the XY plane is at equilibrium, which balances with the optical field trapping forces F5 and F6 from each core to complete the stable stretching of the cells.
[0014] The excitation beam is injected into the central core of the multi-core optical fiber 9 via the attenuator 4-1, the circulator 5, and the multi-core optical fiber fan in/out device 8. The excitation beam transmitted within the central core of the multi-core optical fiber is able to achieve the excitation of the trapped cell's laser via this frustum structure end face. The method is: after the cells are trapped by the beam emitted by the multi-core optical fiber, the microsphere is stretched into a microellipsoid shape by an unevenly distributed optical trap force, which is modulated by the adjustment of the two optical focal points' energy. When the excitation light is excited, the microellipsoid can act as an optical Fabry-Perot microcavity, where the excited laser signal is limited to be in the micro-nanometer level resonator cavity. It can also be understood that the two ends of the long axis of the microellipsoid correspond to the two parallel-placed high-reflective mirrors. Light signals are transmitted back and forth between the mirrors, and light propagating near the axis is reflected back and forth to form a standing wave, which is amplified by the feedback light to form a laser then output the cavity. But due to that generally in the experiment, the two parallel-placed mirrors are not absolutely stable, and is extremely sensitive to the small vibrations from the surrounding environment or other external conditions, if the resonant cavity has a small angle deflection, then after many reflections the light signal, which is transmitted back and forth in the resonant cavity, can easily overflow out of the cavity. Hence, a low-threshold laser such as a cellular laser requires a relatively stable Fabry-Perot microcavity. The microellipsoid is manipulated by a centrally symmetrical structured light field distribution, so it is stretched into a regular ellipsoidal shape, and the stability conditions can be theoretically calculated by means of an ABCD matrix.
M [A BI C DIThe stability condition to be met is:
-1 < _<A+D <1j<~c (2) (2 )
[0015] In the resonant cavity of the Fabry-Perot cavity based cellular laser, the light has to pass twice through the mirror and the cell, respectively, and its incident light transmission matrix M1 in the cavity is
Mi= L 1lL-2R]F nel -no 1 2R]F 0 ncell I[ 0to 1)no-ncell no (3) Rno no Rncell ncel
The reflected light transmission matrix M 2 is
M2 F1 Lncell-no 0 ncell 1F 0 2R 1 no-ncell no 1 0 L-2R] 1 (4) Rno no Rnel neeII
In the above equation, R is the stability conditions for the cell radius to calculate resonant cavity, ncel is the effective refractive index of the substances in the cell, and no is the refractive index of the cell's external environment. The cellular laser outputs a weak laser signal with a lower threshold than conventional lasers, which is in line with future applications in biomedicine. So the threshold is an important parameter for cellular lasers. The gain provided by a regular unit length of fluorescent material is g(z)=N W(z)r -+us U-SS (5)
Where N is the molecular concentration of the fluorescent material, r is the fluorescence lifetime,
c is the speed of light propagation in vacuum, and uss is the absorption cross-section
corresponding to the laser wavelength. Among them
B= E (6)
W(z) = J(z)UO (7) ho
Where n is the refractive index of the laser medium, J(z) is the varying function of the pumping
intensity in the Z-axis direction, Uo is the absorption cross-section corresponding to the
pumping wavelength, ho is the photon energy, E() is the linear function of spontaneous
radiation, and
fE( Ad A =# (8) 0
Where # is the quantum yield. The signal light intensity of one round-trip in the cavity can be
measured by
dI -= I(z)g(z) (9) dz
When the threshold is reached, the light intensity of one round-trip within the cavity is equal to
the initial light intensity, and this method is used to calculate the threshold of the cellular laser,
but in experiments the threshold is often determined by the fitting curve of the measured data.
FIG. 6 is a schematic diagram of the working principle of the Fabry-Perot resonant cavity
microspheres, which limits the light field in such a way that the light intensity in the cavity is
very high, and this can effectively improve the pumping efficiency, thus greatly reducing the
laser threshold, and can largely meet the needs of applications in cell biology.
[0016] The multi-core optical fiber fan in/out device 8 can be understood as a device capable of
splitting the emitting beam into a plurality of different splitting branches that can be coupled into each of the fiber cores of the multi-core optical fiber, wherein each of the splitting branches can in turn be individually controlled by the attenuator 4.
[0017] The schematic diagram of the working principle of a multi-core optical fiber cellular laser system with stretching function is shown in FIG. 1. In order to meet the needs of various sensing measurements, the present invention can replace the microsphere with a single biological cell so that a cellular laser based on a multi-core optical fiber can be achieved.
[0018] The invention has at least the following distinct advantages.
[0019] (1) A cellular laser is proposed. Compared to other single cell plasma lasers that have been proposed, the proposed laser of this invention has the characteristics of non-invasive and the achievement of real-time laser spectral detection.
[0020] (2) The present invention combines single cell trapping techniques, stretching function and a cellular laser to apply to the same multi-core optical fiber. It can provide a wealth of information on cell structure and chemical composition. Thus, the present invention enables the analysis of single cells in a comprehensive and multifunctional manner.
[0021] (3) The proposed optical fiber probe integrates a plurality of operational functions within a single fiber, and the optical fiber probe has the characteristics of high integration and operational flexibility, and this enables quick analysis of living single cells.
BRIEF DESCRIPTION OF DRAWINGS[0022] FIG. 1 is a schematic diagram of a multi-core optical fiber cellular laser system device
with stretching function.
[0023] FIG. 2 is a schematic diagram of the structure and refractive index distribution of a multi
core optical fiber, and the types of light passing through the waveguide in each fiber core.
[0024] FIG. 3 shows a shape optimization scheme of an optical fiber cone-frustum: (a) pre
optimized optical fiber cone-frustum; (b) post-optimized optical fiber cone-frustum.
[0025] FIG. 4 is a schematic diagram of a rotationally symmetrical multi-angle cone-frustum
structure of a multi-core optical fiber end.
[0026]FIG. 5 is a schematic diagram of the microspheres receiving forces when the two light
beams emitted from the multi-core optical fiber is combining a light field.
[0027] FIG. 6 is a schematic diagram of the atlas of the laser signal received according to the
Fabry-Perot resonant microcavity working principle.
[0028] FIG. 7 is a schematic diagram of a five-core optical fiber cellular laser system device with
stretching function.
[0029] FIG. 8 is a schematic diagram of the working principle of a linearly-distributed five-core
optical fiber cellular laser measuring the laser of a single living cell.
[0030] FIG. 9 is a schematic diagram of the working principle of a triangularly-distributed seven-core optical fiber cellular laser measuring the laser of a single living cell.
DESCRIPTION OF EMBODIMENTS[0031] As we know, cell biology remains an important discipline in the life sciences field, underpinning the development of biotechnology foundation. Although cells have been discovered for over 300 years, humans currently do not have a complete and clear understanding of the working mechanisms by which the cell works at an overall level. Cell biology is the study of the basic laws of cellular life activity from the different structural levels of the cell. The use of modern scientific and technological achievements, methods, and concepts, at the cellular level to reveal the information inside the cell, is one of the important ways to acquire cell biological information.
[0032] Living single cell technology is at the forefront of current biological technology and can provide scientists with much new biological information. Not only can the conclusions of past classical methods be tested, but many new patterns can be discovered. For example, the single cell technique first allows scientists to test whether there really is an indicator of cellular mean, which means that the reliability of the multicellularity research methodology of the past can be tested, and how accurate this traditional research technique is. In addition, single cell assays can be very informative, sometimes unanticipated, or information that was previously obscured by statistical results. Not only can single cell studies compensate for the previously obscured and omitted important information as a result from population sampling of cells, but they also enable "histological" results of the research to be more objective and comprehensive. Also, it is possible to discover new phenomena and patterns that have not yet been discovered in life sciences research, thus, it is of particular importance for research in the life sciences.
[0033] For decades, researchers have focused on the analysis of cell populations. An important
premise for conducting such studies is that the individual cells that are thought to make up these
cell populations (e.g., normal tissue cells and tumor cells) are more or less homogeneous or
identical, the results obtained are the average of these cell populations' characteristics. In recent
years, single cell analysis techniques have received increasing attention as the phenomenon of
cellular heterogeneity has been revealed. However, single cell analysis faces many problems.
The most challenging one is the difficulty in meeting the demand for sensitivity, whether it is for
a single specific macromolecule or to conduct molecular analysis at the histological level, all of
which suffer from the difficulty with small amounts of single cell extracts that are difficult, if not
impossible, to analyze.
[0034] Due to limitations in sensitivity and sample volume, the usual life science research is
focused on large numbers of cells. However, there is significant microscopic inhomogeneity
(heterogeneity) between different individuals of the same cell species, and experimental results
based on a large number of cells hardly reflect the patterns of life activity at the single cell level.
Therefore, analysis based on living single cells will be able to reveal the nature and laws of life
activities at a deeper level, and provide a more reliable scientific basis for investigating the
causes, development and treatment of major diseases.
[0035] A multi-core optical fiber cellular laser system with stretching function is used as an
example to illustrate the invention in detail.
[0036] Embodiment 1: a linearly-distributed five-core optical fiber cellular laser measuring the
laser of a single living cell:
[0037] FIG. 7 is a schematic diagram of a multi-core optical fiber cellular laser system device
with stretching function, in the laser system: the trapping beam is extracted from the trapping light source 2 by a standard single-mode optical fiber 6, divided into N paths of light via a 1xN coupler 3, respectively passing through attenuators 4-2 to 4-N and the multi-core optical fiber fan in/out device 8, then into any core but the central core of the multi-core optical fiber 9. The excitation light beam is extracted from the excitation light source 1 by the standard single-mode optical fiber 6, enters the multi-core optical fiber fan in/out device 8 through the attenuator 4-1 and circulator 5, and then enters the central core of the multi-core optical fiber 9. The sample pool filled with liquid with cells is stabilized on the stage 11, and the fiber optical tweezers 10 are immersed in the sample pool, which is used to achieve the trapping and manipulation of the cell by a multi-core optical fiber probe, and the precise displacement operation process is carried out through the real-time imaging by the imaging module composed of a imaging amplifying system 12, a CCD 13 and a computer 14. At the same time, the detected cellular laser signal is received by the spectrograph 7 via a triple-end circulator 5. The cells in the liquid are trapped by the fiber optical tweezers 10 with a rotationally symmetrical cone-frustum-shaped fiber end, through the joint manipulation of the trapping forces of the fiber optical tweezers, achieving position adjustment and the stretching of the attitude of the cells, making the excitation light emitted by the central core and the resonant cell precisely dock, which satisfies the conditions of providing an excitation light source to the cell resonant cavity and outputting the resonance enhanced fluorescence signal to be detected, thereby self-assembling into a new type of "fiber cell" laser. In the "fiber-cell" laser system structure, multiple waveguides play a role in the photodynamic trapping and stretching of the cells, and the central core waveguide provides an excitation light to the trapped cells. This enables emitted excitation late to couple with the stretched microspheres in the cells, thereby achieving resonant excitation of the microspheres and the output of laser signals, completing the sensing and measurement of small changes in the refractive index of the cytosol inside the cells and other parameters.
[0038] As shown in FIG. 8, the cell used here is the HEK293 Human Embryonic Kidney Cells
15, which are commonly used in biology to perform transfected mammalian cells. The cell
diameter is 13.8[tm, which is organically integrated from the gain medium: green fluorescent
protein molecules into cells. When the system is operating, the wavelength of the trapping beam
17 is 980nm, the wavelength of the excitation beam 18 is 480nm, and the two light beams are admitted into the central core and other cores of the multi-core optical fiber 9, respectively. The fiber core light beam admitted by the 980nm trapping light achieves optical reflection at the cone-frustum, and converges to form an optical trap at a distance from the end face of the fiber, to precisely manipulate and regulate the cell attitude of the trapped cells through respectively adjusting the light intensity in the cores. The 480nm excitation light 18 is admitted to the central core, when the position adjusted by the cell satisfies the oscillation conditions of the excitation light emitted by the gain medium microellipsoid 16 in the cell 15 and the central core waveguide, the laser signal generated by the excitation of the gain medium is continuously amplified by the microsphere resonant cavity, when the gain is greater than the total loss of the cavity, a laser output is formed, the laser signal 19 is received through the return of the central core where the excitation beam is located at and then transmitted to the circulator 5; finally the feedback path is completed by the spectrograph 7 to obtain the cellular laser spectrogram.
[0039] Embodiment 2: A triangularly-distributed seven-core optical fiber cellular laser measuring the laser of a single living cell.
[0040] This system has the same device composition as the linearly-distributed five-core optical fiber cellular biosensor, since the number and distribution of the fiber cores have changed, the trapping light 17 and excitation light 18 in the system enters the multi-core optical fiber fan in/out device 8 via a 1x6 coupler 3, respectively. Then they are injected into the corresponding fiber core, in which fiber core bcdefg are fiber cores with trapping functions, and the trapping light 17 is injected; fiber core a is thefiber core with excitation function, and the excitation light 18 is injected. The cell used here is the HEK293 Human Embryonic Kidney Cells 15, when the system is working, the wavelength of the trapping light 17 is chosen as 980nm, and the wavelength of the excitation light 18 is chosen to be 480nm. All cores but the central core can achieve the function of precisely controlling and regulating the cellular attitude of the trapped cells by individually control the attenuator 4, and in the meantime, the central core is used to excite the cell laser light. The laser signal 19 in the cell is received through the return of the central core where the excitation beam is located at and then transmitted to the circulator 5; finally the feedback path is completed by the spectrograph 7 to obtain the cellular laser spectrogram, as shown in FIG. 9.