CN103682966B - A kind of living cells biolaser based on hollow-core photonic crystal fiber carrier - Google Patents
A kind of living cells biolaser based on hollow-core photonic crystal fiber carrier Download PDFInfo
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- CN103682966B CN103682966B CN201310633590.7A CN201310633590A CN103682966B CN 103682966 B CN103682966 B CN 103682966B CN 201310633590 A CN201310633590 A CN 201310633590A CN 103682966 B CN103682966 B CN 103682966B
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- 239000000835 fiber Substances 0.000 title claims abstract description 54
- 239000004038 photonic crystal Substances 0.000 title claims abstract description 52
- 230000003287 optical effect Effects 0.000 claims abstract description 53
- 108091006047 fluorescent proteins Proteins 0.000 claims abstract description 35
- 102000034287 fluorescent proteins Human genes 0.000 claims abstract description 35
- 238000005086 pumping Methods 0.000 claims abstract description 27
- 239000013307 optical fiber Substances 0.000 claims abstract description 9
- MURGITYSBWUQTI-UHFFFAOYSA-N fluorescin Chemical compound OC(=O)C1=CC=CC=C1C1C2=CC=C(O)C=C2OC2=CC(O)=CC=C21 MURGITYSBWUQTI-UHFFFAOYSA-N 0.000 claims description 34
- 230000010473 stable expression Effects 0.000 claims description 28
- 239000005090 green fluorescent protein Substances 0.000 claims description 12
- 108010043121 Green Fluorescent Proteins Proteins 0.000 claims description 6
- 102000004144 Green Fluorescent Proteins Human genes 0.000 claims description 6
- 230000001427 coherent effect Effects 0.000 claims description 5
- 230000002269 spontaneous effect Effects 0.000 claims description 5
- 230000003595 spectral effect Effects 0.000 claims description 4
- 230000000149 penetrating effect Effects 0.000 claims description 3
- 238000007747 plating Methods 0.000 claims description 3
- 230000010412 perfusion Effects 0.000 claims 1
- 238000005516 engineering process Methods 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 56
- 239000010408 film Substances 0.000 description 9
- 239000012788 optical film Substances 0.000 description 4
- 102000006830 Luminescent Proteins Human genes 0.000 description 3
- 108010047357 Luminescent Proteins Proteins 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 241001062009 Indigofera Species 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 108010054624 red fluorescent protein Proteins 0.000 description 2
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
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- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
Landscapes
- Optical Modulation, Optical Deflection, Nonlinear Optics, Optical Demodulation, Optical Logic Elements (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Lasers (AREA)
Abstract
The invention discloses a kind of living cells biolaser based on hollow-core photonic crystal fiber carrier, belong to laser technology and bio-photon field.This laser instrument includes pumping source, optical alignment system, living cells gain medium, hollow-core photonic crystal fiber and optical element；Pump light enters optical alignment system collimation, focus on gain media, gain media is the living cells of express fluorescent protein, by the photonic crystal fiber two ends of filling living cells plus high plane of reflection reflecting mirror, makes optical fiber form optical resonator between two minute surfaces.The present invention applies novel photonic crystal fiber optical resonator to make living cells produce laser, utilizes photonic crystal fiber simultaneously, can accommodate multiple cell in resonator cavity, and the fluorescence intensity of generation is greatly enhanced, and the laser sent is easy to detect record.
Description
Technical field
The invention discloses living cells biolaser, belong to laser technology and lead with bio-photon
Territory, particularly relates to a kind of living cells biolaser based on hollow-core photonic crystal fiber carrier.
Background technology
The concept of unicellular organism laser instrument (single-cell biological laser) be initially by
MalteC.Gather and the Seok Hyun Yun of Harvard University's medical college was at 2011 6
Propose on moon Nature Photonics.Cell biological laser instrument is mainly by green glimmering
The stimulated radiation principle of photoprotein (GFP).These two American scientist profits of Gather and Yun
With Gene transfer techniques, make the human kidney cell can spontaneous synthesis GFP molecule.Then,
The living cells expressing GFP is placed in their distance between the mirror of two sides only just correspond to
The width of one cell, i.e. only has about 20 μm.Subsequently, by the about 1 low-yield indigo plant receiving joule
Light pulse, as exciting light, carrys out the GFP in activated cell.Under normal circumstances, blue light can make
GFP sends green fluorescence in cell, but the fluorescence sent dissipates to all directions randomly.
But at the close high q-factor optical resonance intracavity formed by two panels optical lens, light quilt
Rebound back and forth, the transmitting of GFP is enlarged into a branch of coherent green glow.Although this laser is very
Faint, but can be clearly detected, and still survive for generating this cell of laser.
Gather and Yun have employed spectrum physics company (Spectra Physics in their experiment
Lasers) a kind of optical parametric oscillator Quarta-Ray MOPO-700 series produced, it can be
The output linewidth laser less than 1cm in 400-2000nm tuning range, single pulse energy can be big
In 100mJ.The pumping wavelength of this optical parametric oscillator is 355nm, is by a Nd:YAG
The triple-frequency harmonics of laser instrument produces.
Summary of the invention
It is an object of the invention to there are provided a kind of based on hollow-core photonic crystal fiber carrier
Living cells biolaser, it is by the living cells of hollow-core photonic crystal fiber Yu express fluorescent protein
Combine, both can utilize the unique waveguiding structure of photonic crystal fiber and distinctive optical
Matter, it is also possible to utilize spectral characteristic that fluorescin is good and the high spy of fluorescent quantum efficiency
Point；The present invention uses blue light or green (light) laser as pumping source, will utilize air-core photonic simultaneously
The characteristic property of crystal optical fibre, by stable expression of fluorescent protein (green fluorescent protein or red glimmering
Photoprotein or other fluorescin) Cell infusion in hollow-core photonic crystal fiber chamber, then
Utilize blue light or green (light) laser that the cell in optical fiber is carried out pumping, be finally reached generation and live thin
The purpose of born of the same parents' biology laser；The special construction of hollow-core photonic crystal fiber is plus the high reflection at two ends
Rate plane mirror becomes an optical cavity preferably including multiple cell；Intracavity
After the cell of stable expression of fluorescent protein is irradiated by light source, at such optical resonance intracavity, light
Line is rebounded back and forth, and the spontaneous emission of fluorescin is enlarged into a branch of coherent laser.
The living cells laser instrument that the present invention develops compares with previously described unicellular laser instrument,
Difference is the difference of optical resonator significantly；It utilizes novel band gap type hollow photon crystal
The design of fiber resonance cavity, because multiple cell can be irrigated in optical fiber, fluorescent protein emission
Light will be further magnified, and form stronger laser emission, and in prior art, employing equal
It is the Resonator design of two sides mirror formation, a cell between mirror, can only be accommodated.
For achieving the above object, the technical solution used in the present invention is a kind of brilliant based on air-core photonic
The living cells biolaser of body optic fibre carrier, this laser instrument includes that laser pumping source, optics are accurate
Lineal system, gain medium, hollow-core photonic crystal fiber and optical element；Specifically,
Laser pumping source uses blue light or green glow pumping source, pumping source can export continuously or
Pulse exports；Optical alignment system is two or single lens, or graded index (GRIN)
Lens；Gain medium is stable expression of fluorescent protein (green fluorescent protein or red fluorescence
Albumen or other fluorescin) living cells, fluorescin has quasi-fore-lever structure, spectrum
Characteristic is good and fluorescent quantum efficiency is high；Hollow-core photonic crystal fiber irrigates laser gain
Medium i.e. can the living cells of stable expression of fluorescent protein, this living cells can be that human body is different
Tissue or the cell line of organ origin, as long as can expressing green fluorescent protein, red fluorescence egg
White or other fluorescin；Optical element includes that preposition plane mirror, rearmounted plane are anti-
Penetrate mirror, the preposition plane mirror at hollow-core photonic crystal fiber two ends and rearmounted plane mirror
The film of upper plating is the anti-reflection blooming of the pump light to laser pumping source or the total reflection light to laser
Learn film.
The pump light (blue light or green glow) of laser pumping source collimates through optical alignment system, gathers
Burnt on gain medium, the living cells of the i.e. stable expression of fluorescent protein of gain medium fills
Noting in the photonic crystal fiber cavity of hollow, photonic crystal fiber two ends add two high reflections
The most preposition plane mirror of plane mirror and rearmounted plane mirror, make optical fiber at two minute surfaces
Between formed optical resonator；Gain medium in the photonic crystal fiber cavity of hollow is the most steady
Determining after the living cells of express fluorescent protein irradiated by light source, at optical resonance intracavity, light is come
Return bounce-back, the spontaneous emission of fluorescin is enlarged into a branch of coherent laser light, thus realizes expressing
The living cells biology laser output of fluorescin.
Compared with prior art, the present invention has the advantages that.
1, the present invention utilizes the living cells of hollow-core photonic crystal fiber and express fluorescent protein to tie mutually
Close, both can utilize the waveguiding structure of photonic crystal fiber uniqueness and distinctive optical property, also
Spectral characteristic that fluorescin is good and the high feature of fluorescent quantum efficiency can be utilized；Will be steady
The living cells determining express fluorescent protein is poured in hollow-core photonic crystal fiber carrier, then utilizes
Blue light or green (light) laser carry out pumping to the cell in photonic crystal fiber, are finally reached product
The purpose of living cells biology laser.
2, the present invention uses photonic crystal fiber as the carrier of living cells, can also adopt simultaneously
With capillary tube or silicon waveguiding structure；Multiple stable expression of fluorescent protein can be accommodated in resonator cavity
Living cells, the fluorescence intensity of generation can be greatly enhanced, the laser sent be easy to detect record
Meanwhile, the present invention can utilize the cell line that human body different tissues (organ) is originated, and grinds
Study carefully result and can apply to cyto-architectural research, it is also possible to for human diseases diagnosis and
Treatment provides new method and thinking.
3, the cell of the stable expression of fluorescent protein that the present invention uses is real at the laser of long period
In testing, cell is still alive, it is possible to stably express biological activity；At the same time it can also be used for
The biomaterial optical component of research and development a new generation.
Accompanying drawing explanation
Fig. 1 is living cells biolaser structure chart based on hollow-core photonic crystal fiber carrier.
Fig. 2 is the structural representation of embodiment one.
Fig. 3 is the structural representation of embodiment two.
Fig. 4 is the structural representation of embodiment three.
In figure: 1, pumping source, 2, optical alignment system, 3, optical element, 4, photon brilliant
Body optical fiber, 5, the living cells of stable expression of fluorescent protein, 301, preposition plane mirror, 302,
Rearmounted plane mirror.
Detailed description of the invention
The invention will be further described with embodiment below in conjunction with the accompanying drawings.
It is illustrated in figure 1 living cells biolaser based on hollow-core photonic crystal fiber carrier
Structure chart, a kind of living cells biolaser based on hollow-core photonic crystal fiber carrier, this swashs
Light device includes laser pumping source 1, optical alignment system 2, gain medium 5, hollow light
Photonic crystal fiber 4 and optical element 3；Specifically, laser pumping source 1 uses indigo plant
Light or green glow pumping source, pumping source can export or pulse output continuously；Optical alignment system
System 2 is two or single lens, or graded index (GRIN) lens；Laser gain is situated between
Matter 5 is stable expression of fluorescent protein (green fluorescent protein or red fluorescent protein or other fluorescence
Albumen) living cells, fluorescin has quasi-fore-lever structure, and spectral characteristic is good and glimmering
Light quantum efficiency is high；Hollow-core photonic crystal fiber 4 irrigates gain medium 5 i.e. can
The living cells of stable expression of fluorescent protein, this living cells can be human body different tissues or organ
The cell line in source, as long as can expressing green fluorescent protein, red fluorescent protein or other is glimmering
Photoprotein；Optical element 3 includes preposition plane mirror 301, rearmounted plane mirror
302, the preposition plane mirror 301 at hollow-core photonic crystal fiber 4 two ends and rearmounted plane
On reflecting mirror 302, the film of plating is the anti-reflection blooming of the pump light to laser pumping source 1 or to laser
ATR Optical film.
The pump light (blue light or green glow) of laser pumping source 1 is accurate through optical alignment system 2
Directly, focus on gain medium 5, gain medium 5 i.e. stable expression of fluorescent protein
Living cells be poured in photonic crystal fiber 4 cavity of hollow, photonic crystal fiber 4 two ends
Plus two high the most preposition plane mirrors of plane of reflection reflecting mirror 301 and rearmounted plane reflection
Mirror 302, makes optical fiber form optical resonator between two minute surfaces；The photonic crystal fiber of hollow
The gain medium 5 i.e. living cells of stable expression of fluorescent protein in 4 cavitys is irradiated by light source
After, at optical resonance intracavity, light is rebounded back and forth, is amplified by the spontaneous emission of fluorescin
For a branch of coherent laser light.
Embodiment one
Fig. 2 is the structural representation of embodiment one, and in figure, pumping source is blue light or green glow, can
Select output continuously or pulse output；Optical alignment system 2 includes two lens, to light beam
Carry out collimation focusing；Optical element 3 is the preposition plane mirror 301 of plated film and rearmounted plane
Reflecting mirror 302, plated film is the anti-reflection blooming to pump light or the ATR Optical film to laser；
Gain medium 5 is the living cells of stable expression of fluorescent protein；Preposition plane mirror 301
Constitute plane-parallel resonator with rearmounted plane mirror 302, and the photonic crystal fiber 4 of hollow is empty
The gain medium 5 i.e. living cells of stable expression of fluorescent protein of intracavity is in two reflecting mirrors
Centre, and then form laserresonator.
Pump light sequentially passes through optical alignment system 2 and collimates, focuses on gain medium 5 i.e.
On the living cells 5 of stable expression of fluorescent protein, and gain medium 5 the most stably expresses fluorescence
The living cells of albumen is poured in hollow-core photonic crystal fiber 4, and the laser of generation is at laser resonance
After intracavity multiple reflections, exported by rearmounted plane mirror 302.
Embodiment two
Fig. 3 is the structural representation of embodiment two, and in figure, pumping source is blue light or green glow, can
Select output continuously or pulse output；Optical alignment system 2 is lens, enters light beam
Row collimation focusing；Optical element 3 be the preposition plane mirror 301 of plated film and rearmounted plane anti-
Penetrating mirror 302, plated film is the anti-reflection blooming to pump light or the ATR Optical film to laser；
Gain medium 5 is the living cells of stable expression of fluorescent protein；Preposition plane mirror 301
Constitute plane-parallel resonator with rearmounted plane mirror 302, and the photonic crystal fiber 4 of hollow is empty
The gain medium 5 i.e. living cells of stable expression of fluorescent protein of intracavity is in two reflecting mirrors
Centre, and then form laserresonator.
Pump light sequentially passes through optical alignment system 2 and collimates, focuses on gain medium 5 i.e.
On the living cells 5 of stable expression of fluorescent protein, and gain medium 5 the most stably expresses fluorescence
The living cells of albumen is poured in hollow-core photonic crystal fiber 4, and the laser of generation is at laser resonance
After intracavity multiple reflections, exported by rearmounted plane mirror 302.
Embodiment three
Fig. 4 is the structural representation of embodiment three, and in figure, pumping source is blue light or green glow, can
Select output continuously or pulse output；Optical alignment system 2 is graded index (GRIN)
Lens, carry out collimation focusing to light beam；Optical element 3 is the preposition plane mirror of plated film
301 and rearmounted plane mirror 302, plated film is the anti-reflection blooming to pump light or to laser
ATR Optical film；Gain medium 5 is the living cells of stable expression of fluorescent protein；Before
Put plane mirror 301 and rearmounted plane mirror 302 constitutes plane-parallel resonator, and hollow
The gain medium 5 i.e. work of stable expression of fluorescent protein in photonic crystal fiber 4 cavity is thin
Born of the same parents are in the middle of two reflecting mirrors, and then form laserresonator.
Pump light sequentially passes through optical alignment system 2 and collimates, focuses on gain medium 5 i.e.
On the living cells 5 of stable expression of fluorescent protein, and gain medium 5 the most stably expresses fluorescence
The living cells of albumen is poured in hollow-core photonic crystal fiber 4, and the laser of generation is at laser resonance
After intracavity multiple reflections, exported by rearmounted plane mirror 302.
Claims (5)
1. a living cells biolaser based on hollow-core photonic crystal fiber carrier, its feature exists
In: this laser instrument includes laser pumping source (1), optical alignment system (2), gain medium
(5), hollow-core photonic crystal fiber (4) and optical element (3)；Specifically, laser pump (ing)
Source (1) uses blue light pumping source or green glow pumping source, pumping source can export continuously or
Pulse exports；Optical alignment system (2) is two or single lens, or gradient-index lens；
Gain medium (5) is the living cells of stable expression of fluorescent protein, and fluorescin has accurate four energy
Level structure, spectral characteristic is good and fluorescent quantum efficiency is high；Hollow-core photonic crystal fiber (4)
Middle perfusion gain medium (5) i.e. can the living cells of stable expression of fluorescent protein；Optical element
(3) including preposition plane mirror (301), rearmounted plane mirror (302), air-core photonic is brilliant
The preposition plane mirror (301) at body optical fiber (4) two ends and rearmounted plane mirror (302)
The film of upper plating is to the anti-reflection blooming of pump light of laser pumping source (1) or the total reflection light to laser
Learn film；
The pump light of laser pumping source (1) collimates through optical alignment system (2), it is sharp to focus on
In optical gain medium (5), the living cells of gain medium (5) i.e. stable expression of fluorescent protein
Being poured in photonic crystal fiber (4) cavity of hollow, photonic crystal fiber (4) two ends add
Two the most preposition plane mirror of high plane of reflection reflecting mirrors (301) and rearmounted plane mirror
(302) optical fiber, is made to form optical resonator between two minute surfaces；The photonic crystal fiber (4) of hollow
After the living cells of gain medium (5) the i.e. stable expression of fluorescent protein in cavity is irradiated by light source,
At optical resonance intracavity, light is rebounded back and forth, is enlarged into a branch of by the spontaneous emission of fluorescin
Coherent laser light.
A kind of living cells based on hollow-core photonic crystal fiber carrier the most according to claim 1
Biolaser, it is characterised in that: the fluorescin that living cells is expressed is green fluorescent protein or red
Color fluorescin.
A kind of living cells based on hollow-core photonic crystal fiber carrier the most according to claim 1
Biolaser, it is characterised in that: when optical alignment system (2) is two lens, pump light depends on
Secondary collimate through optical alignment system (2), focus on that gain medium (5) is i.e. stable expresses
On the living cells of fluorescin, and the work of gain medium (5) i.e. stable expression of fluorescent protein is thin
Born of the same parents are poured in hollow-core photonic crystal fiber (4), and the laser of generation is the most anti-at laser resonance intracavity
After penetrating, exported by rearmounted plane mirror (302).
A kind of living cells based on hollow-core photonic crystal fiber carrier the most according to claim 1
Biolaser, it is characterised in that: when optical alignment system (2) is lens, pump light depends on
Secondary collimate through optical alignment system (2), focus on that gain medium (5) is i.e. stable expresses
On the living cells of fluorescin, and the work of gain medium (5) i.e. stable expression of fluorescent protein is thin
Born of the same parents are poured in hollow-core photonic crystal fiber (4), and the laser of generation is the most anti-at laser resonance intracavity
After penetrating, exported by rearmounted plane mirror (302).
A kind of living cells based on hollow-core photonic crystal fiber carrier the most according to claim 1
Biolaser, it is characterised in that: when optical alignment system (2) is gradient-index lens, pump
Pu light sequentially passes through optical alignment system (2) and collimates, focuses on gain medium (5) i.e. surely
Determine on the living cells of express fluorescent protein, and gain medium (5) i.e. stable expression of fluorescent protein
Living cells be poured in hollow-core photonic crystal fiber (4), the laser of generation is at laser resonance intracavity
After multiple reflections, exported by rearmounted plane mirror (302).
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| DE102013014277A1 (en) * | 2013-08-27 | 2015-03-05 | Rosenberger Hochfrequenztechnik Gmbh & Co. Kg | Device for coupling pumping light into a fiber and method for producing such a device |
| WO2018125925A1 (en) * | 2016-12-27 | 2018-07-05 | The Regents Of The University Of Michigan | Laser emission based microscope |
| CN112378889B (en) * | 2020-10-12 | 2022-11-25 | 南京师范大学 | Photonic crystal microsphere capillary column for detecting ochratoxin A and preparation method and application thereof |
| CN112152060B (en) * | 2020-10-30 | 2024-06-07 | 电子科技大学 | Photonic crystal micro laser resonant cavity based on Brewster angle |
| CN117554349B (en) * | 2024-01-11 | 2024-03-19 | 中国科学院苏州生物医学工程技术研究所 | Nano integrated optical chip for single molecule sensing and fluorescence detection method |
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