WO2024007503A1 - 一种细胞调控设备 - Google Patents

一种细胞调控设备 Download PDF

Info

Publication number
WO2024007503A1
WO2024007503A1 PCT/CN2022/131027 CN2022131027W WO2024007503A1 WO 2024007503 A1 WO2024007503 A1 WO 2024007503A1 CN 2022131027 W CN2022131027 W CN 2022131027W WO 2024007503 A1 WO2024007503 A1 WO 2024007503A1
Authority
WO
WIPO (PCT)
Prior art keywords
cell
structured light
laser
light
optical fiber
Prior art date
Application number
PCT/CN2022/131027
Other languages
English (en)
French (fr)
Inventor
李西军
Original Assignee
西湖大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 西湖大学 filed Critical 西湖大学
Publication of WO2024007503A1 publication Critical patent/WO2024007503A1/zh

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M35/00Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M31/00Means for providing, directing, scattering or concentrating light
    • C12M31/02Means for providing, directing, scattering or concentrating light located outside the reactor
    • C12M31/06Lenses
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/34Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas

Definitions

  • the present disclosure relates to cell regulation biotechnology, and in particular to a cell regulation device.
  • Cell growth has a time cycle.
  • the unwinding of the double-stranded DNA in the cell nucleus is a very important control process. It controls the protein synthesis process in the cell by controlling the production of RNA. It also controls the cell division and nuclear replication process. If the unwinding of double-stranded DNA in the cell nucleus can be controlled, this is very important in biological research, and is also very important in pathological and even pharmacological research.
  • embodiments of the present disclosure propose a cell regulation device to solve the uncertainty or complexity of cell regulation in the prior art.
  • the present disclosure provides a cell regulating device, which includes a laser light source, an optical channel device and a culture device.
  • Cells to be regulated are arranged in the culture device.
  • the structured light with orbital angular momentum emitted by the laser light source passes through the optical channel device. is coupled to the cell to excite the DNA within the cell.
  • the laser light source includes a laser that emits the structured light with orbital angular momentum; or the laser light source includes a laser and a spatial modulation mechanism, and the Gaussian laser beam emitted by the laser passes through the The spatial modulation mechanism forms the structured light with orbital angular momentum.
  • the laser light source includes a spatial phase plate array and a plurality of lasers.
  • the Gaussian laser beams emitted by all the lasers constitute a Gaussian laser beam array.
  • the Gaussian laser beam array is formed after passing through the spatial phase plate array. Array distributed structured light with orbital angular momentum.
  • the spatial modulation mechanism includes a spatial phase plate or a spatial light modulator.
  • the optical channel device includes a single-mode or multi-mode optical fiber, and the exit end of the optical fiber is provided with a fiber lens; or the optical fiber is stretched to form a gradient optical fiber, and the exit end of the gradient optical fiber is Diameter range is 500nm to 2um.
  • the light channel device includes a hollow probe, a light channel is formed in the hollow probe, and a high-gloss medium layer is provided on the inner wall of the light channel; or, the inside of the light channel is filled with a regulating liquid or culture medium.
  • the material of the high-gloss medium layer includes at least one of SiO2 or CaF2.
  • the light channel device includes at least two lenses, and the structured light with orbital angular momentum passes through all the lenses in sequence and is coupled to the cell.
  • the culture device includes a temperature adjustment mechanism, the culture device is provided with a culture medium for cultivating cells, and the temperature adjustment mechanism can adjust the temperature of the culture medium; the culture device includes an atmosphere adjustment Mechanism, the atmosphere adjustment mechanism can adjust the atmosphere at the cell.
  • the wavelength range of the structured light emitted by the laser light source is 380nm to 3800nm, and the power range of the structured light is 10uW to 100mW.
  • Embodiments of the present disclosure are based on the scientific fact that the DNA double-stranded structure has a single chirality of a right-handed helix and orbital angular momentum.
  • the torque generated by structured light on the micro-nano structure has dual chirality of left-handed and right-handed helices. Structured light with orbital angular momentum is used. , directly stimulates the DNA in the cell nucleus. When the chirality of the torque generated by the structured light is consistent with the right-hand helix of DNA, it accelerates the unwinding of DNA. When the chirality of the moment generated by structured light is opposite to the right-hand helix of DNA, the unwinding of DNA is consistent, reaching Regulate cell growth or other physiological processes. This control is physical control, and the regulatory factors can act directly and only on the cell nucleus, minimizing influence on other physiological processes, and it is easy to operate.
  • Figure 1 is a schematic structural diagram of a cell regulation device according to an embodiment of the present disclosure
  • Figure 2 is a schematic structural diagram of a laser light source according to an embodiment of the present disclosure
  • Figure 3 is another structural schematic diagram of a laser light source according to an embodiment of the present disclosure.
  • Figure 4 is another structural schematic diagram of a laser light source according to an embodiment of the present disclosure.
  • Figure 5 is a schematic structural diagram of a light beam according to an embodiment of the present disclosure.
  • Figure 6 is a schematic structural diagram of a hollow probe according to an embodiment of the present disclosure.
  • the embodiment of the present disclosure relates to a cell regulation device, including a laser light source 1, a light channel device 2 and a culture device 3.
  • Cells to be regulated are arranged in the culture device 3.
  • the laser light source The structured light with orbital angular momentum emitted by 1 is coupled to the cell through the optical channel device 2 to excite the DNA in the cell.
  • Based on the scientific fact that the DNA double-stranded structure has single chirality with a right-handed helix and orbital angular momentum structured light exerts dual chirality on the micro-nano structure, using structured light with orbital angular momentum to directly stimulate the cell nucleus.
  • At least one base ACGT on DNA or some other molecule generates a chiral moment after absorbing part or all of the structured light energy.
  • structured light with right-handed or left-handed chiral orbital angular momentum is selected to inhibit the unwinding of double-stranded DNA and accelerate the unwinding of double-stranded DNA respectively.
  • the laser light source 1 includes a laser 11, which emits the structured light with orbital angular momentum directly to free space or through light coupling; or, as shown in Figure 3, the The laser light source 1 includes a laser 11 and a spatial modulation mechanism 12.
  • the Gaussian laser beam emitted by the laser 11 passes through the spatial modulation mechanism 12 to form the structured light with orbital angular momentum.
  • the laser 11 may be a semiconductor laser.
  • the structured light emitted by the laser light source 1 is a continuous laser or a real pulse laser.
  • the wavelength range of the structured light is 380nm to 3800nm, and the power range of the structured light is 10uW to 100mW.
  • the laser light source 1 includes a spatial phase plate array 13 and a plurality of lasers 11.
  • the Gaussian laser beams emitted by all the lasers 11 constitute a Gaussian laser beam array.
  • the Gaussian laser beam array passes through
  • the spatial phase plate array 13 forms structured light with orbital angular momentum distributed in the array.
  • the laser 11 may be a semiconductor laser or other laser.
  • the spatial modulation mechanism 12 includes a spatial phase plate or a spatial light modulator.
  • the Gaussian laser beam without orbital angular momentum is modulated into structured light with orbital angular momentum under the action of a spatial phase plate or an air-conditioning light modulator, thereby achieving the control of cells, and the air-conditioning modulation mechanism can adjust the structured light according to actual needs.
  • the direction of the orbital angular momentum thereby achieving reliable regulation of the cell.
  • the optical channel device 2 includes a single-mode or multi-mode optical fiber, and the exit end of the optical fiber is provided with an optical fiber lens. Structured light with orbital angular momentum is coupled into the optical fiber from the light source and passes through the optical fiber. The lens is focused and coupled to the cells to be regulated.
  • the Gaussian beams output by the laser 11 are coupled into optical fibers respectively, and then the optical fibers are arranged in an array to output a Gaussian beam array; on one side of a glass or other transparent base half, micro-nano processing technology is used to process a spiral phase plate array On the corresponding side, MEMs technology is used to process the corresponding microlens array; the Gaussian beam fiber array and the spiral phase plate array are aligned, each microlens in the microlens array is aligned with the coupling fiber behind it, and the coupling fiber end face is located at the corresponding lens. 22 focus.
  • the Gaussian laser beam output by each fiber passes through the spiral phase plate and becomes structured light with orbital angular momentum, and is coupled into the corresponding output fiber through the lens 22 .
  • Each fiber in the coupling fiber array outputs a structured light with orbital angular momentum, thus realizing a structured light array.
  • the structured light output by each optical fiber can regulate a cell in a cell culture microwell, achieving large-scale regulation.
  • the optical fiber is stretched to form a graded optical fiber, and the diameter of the exit end of the graded optical fiber ranges from 500nm to 2um.
  • the structured light beam with orbital angular momentum is coupled to one end of the optical fiber.
  • the other end of the optical fiber is removed from the cladding and then corroded to form a fiber lens or stretched at high temperature to become a gradient optical fiber. Its core diameter changes from the original 8um. After a few millimeters to 10um, it becomes between 500nm and 2um, with focusing function.
  • the coupled structured light with orbital angular momentum can be focused onto the cells that need to be controlled by utilizing the focusing lens 22 on the optical fiber and the rear gradient optical fiber. If it is a graded optical fiber, its tip can be inserted into the cell with the cooperation of the microscope and machinery, and the structured light can be directly applied to the cell nucleus.
  • the transmission optical fiber includes an optical fiber core 211 for transmitting light beams, and an optical fiber cladding 212 is provided around the outside of the optical fiber core 211;
  • the optical fiber core 211 and the optical fiber cladding 212 can be It is made of any suitable material with a small absorption coefficient for light beams in the wavelength range of 193nm-2um, for example.
  • the optical fiber core 211 here can be made of doped quartz material.
  • the optical fiber core 211 is made of CaF2 or doped CaF2.
  • the optical fiber cladding 212 here can be non-doped. It is made of quartz material.
  • the optical fiber cladding 212 is made of quartz or CaF2 material.
  • a lens structure 213 is provided outside the exit end of the fiber cladding 212.
  • the lens structure 213 may have an arc-shaped convex structure.
  • the lens structure 213 is used for The exposure laser is caused to form a Gaussian beam spot of a highly focused photolithography beam on the focal plane 214 of the lens structure 213 .
  • the lens structure 213 here may be, for example, a focusing lens 22 for optical fiber exposure; specifically, the lens structure 213 may be a fiber lens formed on the end surface of the optical fiber core 211 using chemical etching or the like, or may be It is a metasurface lens 22 formed on the end surface of the optical fiber cladding 212 using micro-nano processing technology, for example.
  • the optical channel device 2 includes a hollow probe 24, an optical channel is formed in the hollow probe 24, and a high-gloss medium layer is provided on the inner wall of the optical channel; Or, the inside of the light channel is filled with regulating fluid or culture fluid.
  • the light channel device 2 is a hollow scanning probe microscope, and the hollow probe 24 can pierce the cell membrane and cell nucleus and directly enter the cell nucleus with the cooperation of the microscope and control software.
  • a structured beam or light pulse with orbital angular momentum is coupled to the probe channel and propagates directly into the cell nucleus to achieve cell regulation.
  • the material of the high-gloss medium layer includes at least one of SiO2 or CaF2.
  • the light channel device 2 includes at least two lenses 22 , and the structured light with orbital angular momentum passes through all the lenses 22 in sequence and is coupled to the cell.
  • the last lens 22 is the objective lens of the microscope, which is capable of coupling structured light with orbital angular momentum to the cells.
  • the culture device 3 includes a temperature adjustment mechanism.
  • the culture device 3 is provided with a culture medium for cultivating cells.
  • the temperature adjustment mechanism can adjust the temperature of the culture medium; the culture device 3
  • An atmosphere adjustment mechanism is included, and the atmosphere adjustment mechanism is capable of adjusting the atmosphere at the cell.
  • the culture device 3 is used to provide appropriate temperature and/or gas atmosphere for cell culture. Specifically, the temperature adjustment mechanism can adjust the culture medium of the cells, and the culture medium can be renewed.
  • the atmosphere adjustment mechanism can maintain the cells at a mixture of 5% carbon dioxide and air.
  • the culture device 3 also includes a microscope to facilitate monitoring and observing the production and regulation of cells.
  • the cells can be cultured in a Chuangtong culture dish or in a microfluidic flow channel.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Sustainable Development (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Thermal Sciences (AREA)
  • Cell Biology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

本申请提出一种细胞调控设备,包括激光光源、光通道装置和培养装置,所述培养装置内设置有待调控的细胞。本申请依据DNA 双链结构的具有右手螺旋的单一手性、轨道角动量结构光对微纳结构产生的力矩具有左手和右手螺旋双重手性的科学事实,利用具有轨道角动量的结构光,直接刺激细胞核的DNA,结构光产生的力矩的手性与DNA 右手螺旋一致时,加速DNA的解链,结构光产生的力矩的手性与DNA 右手螺旋相反时,抑制DNA的解链,达到调控细胞的生长或其它生理过程。这一调控是物理调控,调控因子可以直接且只作用在细胞核上,实现最大限度地不影响其它生理过程,操作简便。

Description

一种细胞调控设备 技术领域
本公开涉及细胞调控生物技术,尤其涉及一种细胞调控设备。
背景技术
细胞的生长是有时间周期的。在细胞的生长周期内,细胞核内双链结构的DNA的解链是非常重要的控制过程,它通过控制了RNA的生成控制细胞内蛋白质的合成过程,同时也是控制细胞的分裂核复制过程。如果能调控细胞核内双链DNA的解链,这在生物学研究中是非常重要的,在病理甚至药理研究中也是非常重要的。
现在的细胞调控法通常是采用生物或化学分子来调控,但是这些分子需要透过细胞壁才能激励细胞的生理过程,而分子透过细胞壁本身就是一个难把控的生理过程。这个研究带来不确定性或操作的复杂性。
发明内容
有鉴于此,本公开实施例提出了一种细胞调控设备,以解决现有技术中细胞调控所存在的不确定性或复杂性。
本公开提供一种细胞调控设备,包括激光光源、光通道装置和培养装置,所述培养装置内设置有待调控的细胞,所述激光光源发出的具有轨道角动量的结构光通过所述光通道装置的耦合至所述细胞上以激励所述细胞内的DNA。
在一些实施例中,所述激光光源包括激光器,所述激光器发出所述具有轨道角动量的结构光;或,所述激光光源包括激光器和空间调制机构,所述激光器发出的高斯激光束经过所述空间调制机构后形成所述具有轨道角动量的结构光。
在一些实施例中,所述激光光源包括空间相位板阵列和复数个激光器,所有所述激光器发出的高斯激光束构成高斯激光束阵列,所述高斯激光束阵列经过所述空间相位板阵列后形成阵列分布的具有轨道角动量的结构光。
在一些实施例中,所述空间调制机构包括空间相位板或空间光调制器。
在一些实施例中,所述光通道装置包括单模或多模光纤,且所述光纤的出射端设置有光纤透镜头;或,所述光纤拉伸形成渐变光纤,所述渐变光纤的出射端的直径范围为500nm至2um。
在一些实施例中,所述光通道装置包括中空探针,所述中空探针内形成有光通道,所述光通道的内壁上设置有高光介质层;或,所述光通道内部填充有调控液或培养液。
在一些实施例中,所述高光介质层的材料包括SiO2或CaF2中的至少一种。
在一些实施例中,所述光通道装置包括至少两个透镜,所述具有轨道角动量的结构光依次经过所有所述透镜后耦合于所述细胞上。
在一些实施例中,所述培养装置包括温度调节机构,所述培养装置内设置有用于培养细胞的培养液,所述温度调节机构能够调节所述培养液的温度;所述培养装置包括气氛调节机构,所述气氛调节机构能够调节所述细胞处的气氛。
在一些实施例中,所述激光光源发出的所述结构光的波长范围为380nm至3800nm,所述结构光的功率范围为10uW到100mW。
本公开实施例依据DNA双链结构的具有右手螺旋的单一手性、轨道角动量结构光对微纳结构产生的力矩具有左手和右手螺旋双重手性的科学事实,利用具有轨道角动量的结构光,直接刺激细胞核的DNA,结构光产生的力矩的手性与DNA右手螺旋一致时,加速DNA的解链,结构光产生的力矩的手性与DNA右手螺旋相反时,一致DNA的解链,达到调控细胞的生长或其它生理过程。这一调控是物理调控,调控因子可以直接且只作用在细胞核上,实现最大限度地不影响其它生理过程,操作简便。
附图说明
为了更清楚地说明本公开实施例或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本公开中记载的一些实施例,对于本领域普通技术人员 来讲,在不付出创造性劳动性的前提下,还可以根据这些附图获得其他的附图。
图1为本公开实施例的细胞调控设备的结构示意图;
图2为本公开实施例的激光光源的一种结构示意图;
图3为本公开实施例的激光光源的另一种结构示意图;
图4为本公开实施例的激光光源的另一种结构示意图;
图5为本公开实施例的光线的结构示意图;
图6为本公开实施例的中空探针的结构示意图。
具体实施方式
为了使得本公开实施例的目的、技术方案和优点更加清楚,下面将结合本公开实施例的附图,对本公开实施例的技术方案进行清楚、完整地描述。显然,所描述的实施例是本公开的一部分实施例,而不是全部的实施例。基于所描述的本公开的实施例,本领域普通技术人员在无需创造性劳动的前提下所获得的所有其他实施例,都属于本公开保护的范围。
除非另外定义,本公开使用的技术术语或者科学术语应当为本公开所属领域内具有一般技能的人士所理解的通常意义。本公开中使用的“第一”、“第二”以及类似的词语并不表示任何顺序、数量或者重要性,而只是用来区分不同的组成部分。“包括”或者“包含”等类似的词语意指出现该词前面的元件或者物件涵盖出现在该词后面列举的元件或者物件及其等同,而不排除其他元件或者物件。“连接”或者“相连”等类似的词语并非限定于物理的或者机械的连接,而是可以包括电性的连接,不管是直接的还是间接的。“上”、“下”、“左”、“右”等仅用于表示相对位置关系,当被描述对象的绝对位置改变后,则该相对位置关系也可能相应地改变。
为了保持本公开实施例的以下说明清楚且简明,本公开省略了已知功能和已知部件的详细说明。
如图1至图6所示,本公开实施例涉及一种细胞调控设备,包括激光光源1、光通道装置2和培养装置3,所述培养装置3内设置有待调控的细胞,所述激光光源1发出的具有轨道角动量的结构光通过所述光通道装置2的耦合至所述细胞上以激励所述细胞内的DNA。依据DNA双链结构的具有右手螺 旋的单一手性、轨道角动量结构光对微纳结构产生的力矩具有左手和右手螺旋双重手性的科学事实,利用具有轨道角动量的结构光,直接刺激细胞核的DNA,结构光产生的力矩的手性与DNA右手螺旋一致时,加速DNA的解链,结构光产生的力矩的手性与DNA右手螺旋相反时,一致DNA的解链,达到调控细胞的生长或其它生理过程。这一调控是物理调控,调控因子可以直接且只作用在细胞核上,实现最大限度地不影响其它生理过程,操作简便。
DNA上的至少一个碱基ACGT或其它某个分子在部分或全部吸收结构光能量后产生具有手性的力矩。依据调控的需要,抑制双链DNA解链和加速双链DNA解链分别选用具有右手或左手手性轨道角动量的结构光。
优选的,所述激光光源1包括激光器11,所述激光器11发出所述具有轨道角动量的结构光,直接向自由空间发出,也可以经过光线耦合发出;或,如图3所示,所述激光光源1包括激光器11和空间调制机构12,所述激光器11发出的高斯激光束经过所述空间调制机构12后形成所述具有轨道角动量的结构光。激光器11可以为半导体激光器。
所述激光光源1发出的所述结构光是连续激光,也可以实脉冲激光。结构光的波长范围为380nm至3800nm,所述结构光的功率范围为10uW到100mW。
更进一步的,如图4所示,所述激光光源1包括空间相位板阵列13和复数个激光器11,所有所述激光器11发出的高斯激光束构成高斯激光束阵列,所述高斯激光束阵列经过所述空间相位板阵列13后形成阵列分布的具有轨道角动量的结构光。其中,激光器11可以为半导体激光器或其他激光器。
在一些实施例中,所述空间调制机构12包括空间相位板或空间光调制器。通过空间相位板或空调光调制器的作用下将不具有轨道角动量的高斯激光束调制成具有轨道角动量的结构光,从而实现对细胞的调控,并且空调调制机构能够根据实际需求调节结构光的轨道角动量的方向,从而实现对细胞的调节可靠。
在一些实施例中,所述光通道装置2包括单模或多模光纤,且所述光纤的出射端设置有光纤透镜头,具有轨道角动量的结构光从光源耦合到光纤中,经光纤透镜头的聚焦后耦合到要调控的细胞上。
具体的,激光器11输出的高斯光束分别耦合到光纤中,再把光纤排成阵列输出高斯光束阵列;在一个玻璃或其它透明基半的一侧,利用微纳加工技术,加工一个螺旋相位板阵列对应的一侧,利用MEMs技术加工出对应的微透 镜阵列;高斯束光纤阵列和螺旋相位板阵列对准,微透镜阵列中每个微透镜和后面的耦合光纤对准且耦合光纤端面位于对应透镜22的焦点。这样每根光纤输出的高斯激光束经过螺旋相位板变成具有轨道角动量的结构光,经过透镜22耦合到对应的输出光纤中。耦合光纤阵列中每根光纤都输出一个具有轨道角动量的结构光,这样就实现结构光阵列。每根光纤输出的结构光可以调控细胞培养microwell中的一个细胞,实现规模化的调控。
或者,所述光纤拉伸形成渐变光纤,所述渐变光纤的出射端的直径范围为500nm至2um。把具有轨道角动量的结构光光束耦合到光纤的一端,该光纤的另一端去掉包层后经过腐蚀形成光纤透镜或带包层在高温下拉伸成为渐变光纤,其芯径从原有的8um到10um经过数毫米后变成500nm到2um之间,具有聚焦功能。利用光纤上的聚焦透镜22后渐变光纤,可以把耦合来的具有轨道角动量的结构光聚焦到需要调控的细胞上。如果是渐变光纤,其针尖可以在显微镜和机械上的配合下插入细胞内,把结构光直接作用到细胞核。
如图5所示,所述传输光纤包括用于传输光束的光纤芯211,在所述光纤芯211的外侧包围设置光纤包层212;这里的所述光纤芯211和所述光纤包层212可以采用适合的例如对193nm-2um波长范围的光束的吸收系数小的任意材料制成。其中,这里的所述光纤芯211可以采用掺杂的石英材料制成,优选地,所述光纤芯211采用CaF2或掺杂的CaF2制成,这里的所述光纤包层212可以采用非掺杂的石英材料制成,优选地,所述光纤包层212采用石英或CaF2材料制成。
在所述光纤包层212的出射端的外侧设置透镜结构213,所述透镜结构213可以具有弧形外凸的结构,在所述透镜结构213的外侧具有焦平面214,所述透镜结构213用于使所述曝光激光在所述透镜结构213的所述焦平面214上形成高度聚焦的光刻光束的高斯束斑。这里的所述透镜结构213例如可以是用于光纤曝光的聚焦透镜22;具体地,所述透镜结构213可以是采用化学刻蚀法等在所述光纤芯211的端面上形成光纤透镜,也可以是采用例如微纳加工技术在所述光纤包层212的端面上形成的超表面透镜22。
如图6所示,作为另一种实施例,所述光通道装置2包括中空探针24,所述中空探针24内形成有光通道,所述光通道的内壁上设置有高光介质层;或,所述光通道内部填充有调控液或培养液。
具体的,光通道装置2为中空的扫描探针显微镜,中空探针24可以在显 微镜和控制软件的协同下刺破细胞膜和细胞核,直接进入细胞核。具有轨道角动量的结构光束或光脉冲耦合到探针通道,直接传播到细胞核内,实现对细胞的调控。
优选的,所述高光介质层的材料包括SiO2或CaF2中的至少一种。
在一些实施例中,所述光通道装置2包括至少两个透镜22,所述具有轨道角动量的结构光依次经过所有所述透镜22后耦合于所述细胞上。其中,最后一个透镜22是显微镜的物镜,该物镜能够将具有轨道角动量的结构光耦合到细胞上。
在一些实施例中,所述培养装置3包括温度调节机构,所述培养装置3内设置有用于培养细胞的培养液,所述温度调节机构能够调节所述培养液的温度;所述培养装置3包括气氛调节机构,所述气氛调节机构能够调节所述细胞处的气氛。利用培养装置3为细胞的培养提供合适的温度和/或气体气氛。具体的,温度调节机构能够调节细胞的培养液,其中培养液能更新。气氛调节机构能够保持细胞处于5%的二氧化碳和空气混合气等。
更为具体的是,培养装置3还包括显微镜,便于监控和观察细胞的生产和调控。
优选的,细胞可以培养在创通的培养皿中,也可以培养在微流控的流道中。
以上描述仅为本公开的较佳实施例以及对所运用技术原理的说明。本领域技术人员应当理解,本公开中所涉及的公开范围,并不限于上述技术特征的特定组合而成的技术方案,同时也应涵盖在不脱离上述公开构思的情况下,由上述技术特征或其等同特征进行任意组合而形成的其它技术方案。例如上述特征与本公开中公开的(但不限于)具有类似功能的技术特征进行互相替换而形成的技术方案。
此外,虽然采用特定次序描绘了各操作,但是这不应当理解为要求这些操作以所示出的特定次序或以顺序次序执行来执行。在一定环境下,多任务和并行处理可能是有利的。同样地,虽然在上面论述中包含了若干具体实现细节,但是这些不应当被解释为对本公开的范围的限制。在单独的实施例的上下文中描述的某些特征还可以组合地实现在单个实施例中。相反地,在单个实施例的上下文中描述的各种特征也可以单独地或以任何合适的子组合的方式实现在多个实施例中。
尽管已经采用特定于结构特征和/或方法逻辑动作的语言描述了本主题,但是应当理解所附权利要求书中所限定的主题未必局限于上面描述的特定特征或动作。相反,上面所描述的特定特征和动作仅仅是实现权利要求书的示例形式。
以上对本公开多个实施例进行了详细说明,但本公开不限于这些具体的实施例,本领域技术人员在本公开构思的基础上,能够做出多种变型和修改实施例,这些变型和修改都应落入本公开所要求保护的范围。

Claims (10)

  1. 一种细胞调控设备,其特征在于,包括激光光源、光通道装置和培养装置,所述培养装置内设置有待调控的细胞,所述激光光源发出的具有轨道角动量的结构光通过所述光通道装置的耦合至所述细胞上以激励所述细胞内的DNA。
  2. 根据权利要求1所述的细胞调控设备,其特征在于,所述激光光源包括激光器,所述激光器发出所述具有轨道角动量的结构光;或,所述激光光源包括激光器和空间调制机构,所述激光器发出的高斯激光束经过所述空间调制机构后形成所述具有轨道角动量的结构光。
  3. 根据权利要求1所述的细胞调控设备,其特征在于,所述激光光源包括空间相位板阵列和复数个激光器,所有所述激光器发出的高斯激光束构成高斯激光束阵列,所述高斯激光束阵列经过所述空间相位板阵列后形成阵列分布的具有轨道角动量的结构光。
  4. 根据权利要求2所述的细胞调控设备,其特征在于,所述空间调制机构包括空间相位板或空间光调制器。
  5. 根据权利要求1所述的细胞调控设备,其特征在于,所述光通道装置包括单模或多模光纤,且所述光纤的出射端设置有光纤透镜头;或,所述光纤拉伸形成渐变光纤,所述渐变光纤的出射端的直径范围为500nm至2um。
  6. 根据权利要求1所述的细胞调控设备,其特征在于,所述光通道装置包括中空探针,所述中空探针内形成有光通道,所述光通道的内壁上设置有高光介质层;或,所述光通道内部填充有调控液或培养液。
  7. 根据权利要求6所述的细胞调控设备,其特征在于,所述高光介质层的材料包括SiO2或CaF2中的至少一种。
  8. 根据权利要求1所述的细胞调控设备,其特征在于,所述光通道装置包括至少两个透镜,所述具有轨道角动量的结构光依次经过所有所述透镜后耦合于所述细胞上。
  9. 根据权利要求1所述的细胞调控设备,其特征在于,所述培养装置包括温度调节机构,所述培养装置内设置有用于培养细胞的培养液,所述温度调节机构能够调节所述培养液的温度;所述培养装置包括气氛调节机构,所述气氛调节机构能够调节所述细胞处的气氛。
  10. 根据权利要求1所述的细胞调控设备,其特征在于,所述激光光源发 出的所述结构光的波长范围为380nm至3800nm,所述结构光的功率范围为10uW到100mW。
PCT/CN2022/131027 2022-07-08 2022-11-10 一种细胞调控设备 WO2024007503A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202210805812.8A CN115011463A (zh) 2022-07-08 2022-07-08 一种细胞调控设备
CN202210805812.8 2022-07-08

Publications (1)

Publication Number Publication Date
WO2024007503A1 true WO2024007503A1 (zh) 2024-01-11

Family

ID=83081396

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/131027 WO2024007503A1 (zh) 2022-07-08 2022-11-10 一种细胞调控设备

Country Status (2)

Country Link
CN (1) CN115011463A (zh)
WO (1) WO2024007503A1 (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115011463A (zh) * 2022-07-08 2022-09-06 西湖大学 一种细胞调控设备

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102414555A (zh) * 2009-03-26 2012-04-11 波士顿大学董事会 在两液体间的薄固态界面上成像的方法
CN103392008A (zh) * 2010-09-07 2013-11-13 加利福尼亚大学董事会 通过持续性酶以一个核苷酸的精度控制dna在纳米孔中的移动
CN112002454A (zh) * 2020-09-14 2020-11-27 桂林电子科技大学 全光纤可调微粒搅拌装置
CN114486687A (zh) * 2022-01-27 2022-05-13 北京理工大学 飞秒激光加工细胞的多尺度连续观测反馈方法及装置
CN115011463A (zh) * 2022-07-08 2022-09-06 西湖大学 一种细胞调控设备

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102414555A (zh) * 2009-03-26 2012-04-11 波士顿大学董事会 在两液体间的薄固态界面上成像的方法
CN103392008A (zh) * 2010-09-07 2013-11-13 加利福尼亚大学董事会 通过持续性酶以一个核苷酸的精度控制dna在纳米孔中的移动
CN112002454A (zh) * 2020-09-14 2020-11-27 桂林电子科技大学 全光纤可调微粒搅拌装置
CN114486687A (zh) * 2022-01-27 2022-05-13 北京理工大学 飞秒激光加工细胞的多尺度连续观测反馈方法及装置
CN115011463A (zh) * 2022-07-08 2022-09-06 西湖大学 一种细胞调控设备

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"Master’s Theses", 1 May 2019, WUHAN UNIVERSITY, China, article SONG, CHONGYANG: " Real-Time DNA Detection Based on Optical Tweezers and Upconversion Luminescent Labeling", pages: 1 - 68, XP009551620, DOI: 10.27379/d.cnki.gwhdu.2019.001437 *

Also Published As

Publication number Publication date
CN115011463A (zh) 2022-09-06

Similar Documents

Publication Publication Date Title
WO2024007503A1 (zh) 一种细胞调控设备
US6346101B1 (en) Photon-mediated introduction of biological materials into cells and/or cellular components
Waleed et al. Single-cell optoporation and transfection using femtosecond laser and optical tweezers
Paterson et al. Photoporation and cell transfection using a violet diode laser
US8076632B2 (en) Device and method for the contactless manipulation and alignment of sample particles in a measurement volume using a nonhomogeneous electric alternating field
CN109641468A (zh) 用于激光诱导的材料分配的套件和系统
Chen et al. Laser-induced fusion of human embryonic stem cells with optical tweezers
Ma et al. Integrated optical transfection system using a microlens fiber combined with microfluidic gene delivery
Stevenson et al. Optically guided neuronal growth at near infrared wavelengths
CN104678546A (zh) 一种光纤光开关
Yashunin et al. Fabrication of microchannels in fused silica using femtosecond Bessel beams
CN109799571A (zh) 基于环形芯同轴螺旋波导光纤的粒子光操纵器件
EP2580337B1 (en) Optical transfection
Wu et al. Multifunctional single-fiber optical tweezers for particle trapping and transport
US9249385B1 (en) System and method for fusing cells
US8318494B2 (en) Genetic material and chromosomal processing and manipulation methods
RU2495932C1 (ru) Способ лазерного слияния бластомеров внутри ранних доимплантационных эмбрионов млекопитающих без нарушения их целостности
CN103033920B (zh) 远红外温度跃升显微镜
CN115182046B (zh) 一种制备倍半氧化物单晶光纤包层的方法
Berns et al. Micromanipulation of chromosomes and the mitotic spindle using laser microsurgery (laser scissors) and laser-induced optical forces (laser tweezers)
CN112711132B (zh) 一种单细胞手术装置
Torres-Mapa et al. Femtosecond optical transfection as a tool for genetic manipulation of human embryonic stem cells
Shakhbazyan et al. Obtainment of chimeric blastocysts of mice by methods of laser nanosurgery
CN113534340B (zh) 光子集成芯片上的手性轨道角动量发射器
CN113528343B (zh) 一种用于太赫兹波辐照的贴壁细胞培养器

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22950061

Country of ref document: EP

Kind code of ref document: A1