CN115011463A

CN115011463A - Cell regulation and control equipment

Info

Publication number: CN115011463A
Application number: CN202210805812.8A
Authority: CN
Inventors: 李西军
Original assignee: Westlake University
Current assignee: Westlake University
Priority date: 2022-07-08
Filing date: 2022-07-08
Publication date: 2022-09-06
Also published as: WO2024007503A1

Abstract

The embodiment of the disclosure provides a cell regulation and control device, which comprises a laser light source, a light channel device and a culture device, wherein cells to be regulated and controlled are arranged in the culture device. According to the scientific fact that the single chirality of the right-handed helix of the DNA double-chain structure and the orbital angular momentum structural light have the double chirality of the left-handed helix and the right-handed helix to the moment generated by the micro-nano structure, the structural light with the orbital angular momentum is utilized to directly stimulate the DNA of the cell nucleus, when the chirality of the moment generated by the structural light is consistent with the right-handed helix of the DNA, the unzipping of the DNA is accelerated, and when the chirality of the moment generated by the structural light is opposite to the right-handed helix of the DNA, the unzipping of the consistent DNA is realized, so that the growth of cells or other physiological processes are regulated and controlled. The regulation is physical regulation, the regulation factor can directly act on the cell nucleus only, other physiological processes are not influenced to the maximum extent, and the operation is simple and convenient.

Description

Cell regulation and control equipment

Technical Field

The present disclosure relates to cell regulation biotechnology, and in particular, to a cell regulation apparatus.

Background

The cells are grown with a time cycle. The melting of DNA in the nucleus double-stranded structure is a very important control process during the cell growth cycle, which controls the synthesis of intracellular proteins by controlling the production of RNA, and controls the replication of the dividing nucleus of the cell. This is important in biological studies, and in pathological and even pharmacological studies, if the melting of double-stranded DNA in the nucleus can be controlled.

The current cell regulation method usually adopts biological or chemical molecules for regulation, but the molecules need to penetrate through a cell wall to stimulate the physiological process of cells, and the molecules penetrate through the cell wall to be a physiological process which is difficult to control. This study introduces uncertainty or operational complexity.

Disclosure of Invention

In view of the above, the embodiments of the present disclosure provide a cell regulating device to solve the uncertainty or complexity of cell regulation in the prior art.

The present disclosure provides a cell regulating apparatus, including a laser light source, a light channel device and a culture device, wherein a cell to be regulated is arranged in the culture device, and structured light with orbital angular momentum emitted by the laser light source is coupled to the cell through the light channel device to excite DNA in the cell.

In some embodiments, the laser light source comprises a laser emitting the structured light having orbital angular momentum; or the laser light source comprises a laser and a spatial modulation mechanism, and the structured light with orbital angular momentum is formed by a Gaussian laser beam emitted by the laser after passing through the spatial modulation mechanism.

In some embodiments, the laser light source includes a spatial phase plate array and a plurality of lasers, and gaussian laser beams emitted by all the lasers form a gaussian laser beam array, and the gaussian laser beam array forms structured light with orbital angular momentum distributed in an array after passing through the spatial phase plate array.

In some embodiments, the spatial modulation mechanism comprises a spatial phase plate or a spatial light modulator.

In some embodiments, the optical channel device comprises 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 diameter range of the emergent end of the gradient optical fiber is 500nm to 2 um.

In some embodiments, the optical channel device comprises a hollow probe, an optical channel is formed in the hollow probe, and a high light medium layer is arranged on the inner wall of the optical channel; or the inside of the optical channel is filled with a regulating solution or a culture solution.

In some embodiments, the material of the high optical medium layer includes at least one of SiO2 or CaF 2.

In some embodiments, the light tunnel device comprises at least two lenses, and the structured light with orbital angular momentum is coupled to the cell after passing through all the lenses in sequence.

In some embodiments, the culture device comprises a temperature adjustment mechanism, wherein a culture solution for culturing cells is arranged in the culture device, and the temperature adjustment mechanism can adjust the temperature of the culture solution; the culture device includes an atmosphere adjustment mechanism capable of adjusting an atmosphere at the cell.

In some embodiments, the laser light source emits the structured light with a wavelength ranging from 380nm to 3800nm, and the power of the structured light ranges from 10uW to 100 mW.

According to the scientific fact that the single chirality of the DNA double-stranded structure with the right-handed helix and the orbital angular momentum structural light have the double chirality of the left-handed helix and the right-handed helix on the moment generated by the micro-nano structure, the structural light with the orbital angular momentum is utilized to directly stimulate the DNA of a cell nucleus, when the chirality of the moment generated by the structural light is consistent with the right-handed helix of the DNA, the unwinding of the DNA is accelerated, and when the chirality of the moment generated by the structural light is opposite to the right-handed helix of the DNA, the unwinding of the consistent DNA is realized, so that the regulation and control of the growth of cells or other physiological processes are achieved. The regulation is physical regulation, the regulation factor can directly act on the cell nucleus only, other physiological processes are not influenced to the maximum extent, and the operation is simple and convenient.

Drawings

In order to more clearly illustrate the embodiments of the present disclosure or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments or the prior art will be briefly introduced below, it is obvious that the drawings in the following description are only some embodiments described in the present disclosure, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.

FIG. 1 is a schematic diagram of a cell conditioning apparatus according to an embodiment of the present disclosure;

FIG. 2 is a schematic diagram of a laser light source according to an embodiment of the disclosure;

FIG. 3 is a schematic view of another structure of a laser light source according to an embodiment of the disclosure;

FIG. 4 is a schematic view of another structure of a laser light source according to an embodiment of the disclosure;

FIG. 5 is a schematic diagram of a light ray structure according to an embodiment of the present disclosure;

fig. 6 is a schematic structural diagram of a hollow probe according to an embodiment of the present disclosure.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present disclosure more clear, the technical solutions of the embodiments of the present disclosure will be described below clearly and completely with reference to the accompanying drawings of the embodiments of the present disclosure. It is to be understood that the described embodiments are only a few embodiments of the present disclosure, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the disclosure without any inventive step, are within the scope of protection of the disclosure.

Unless otherwise defined, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this disclosure belongs. The use of "first," "second," and similar terms in this disclosure is not intended to indicate any order, quantity, or importance, but rather is used to distinguish one element from another. The word "comprising" or "comprises", and the like, means that the element or item listed before the word covers the element or item listed after the word and its equivalents, but does not exclude other elements or items. The terms "connected" or "coupled" and the like are not restricted to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "upper", "lower", "left", "right", and the like are used merely to indicate relative positional relationships, and when the absolute position of the object being described is changed, the relative positional relationships may also be changed accordingly.

To maintain the following description of the embodiments of the present disclosure clear and concise, a detailed description of known functions and known components have been omitted from the present disclosure.

As shown in fig. 1 to 6, the embodiment of the present disclosure relates to a cell conditioning apparatus, which includes a laser light source 1, a light channel device 2, and a culture device 3, a cell to be conditioned is disposed in the culture device 3, and structured light with orbital angular momentum emitted by the laser light source 1 is coupled to the cell through the light channel device 2 to excite DNA in the cell. According to the scientific fact that the single chirality of right-handed helix and orbital angular momentum structural light of a DNA double-stranded structure have double chirality of left-handed and right-handed helices on the moment generated by the micro-nano structure, the DNA of a cell nucleus is directly stimulated by the structural light with the orbital angular momentum, when the chirality of the moment generated by the structural light is consistent with the right-handed helix of the DNA, unwinding of the DNA is accelerated, and when the chirality of the moment generated by the structural light is opposite to the right-handed helix of the DNA, unwinding of the consistent DNA is achieved, and the purpose of regulating and controlling the growth of cells or other physiological processes is achieved. The regulation is physical regulation, the regulation factor can directly act on the cell nucleus only, other physiological processes are not influenced to the maximum extent, and the operation is simple and convenient.

At least one base ACGT or some other molecule on DNA generates a chiral moment after partial or complete absorption of the light energy of the structure. According to the need of regulation, structured light with right-handed or left-handed chiral orbital angular momentum is selected respectively for inhibiting the melting of double-stranded DNA and accelerating the melting of double-stranded DNA.

Preferably, the laser light source 1 includes a laser 11, and the laser 11 emits the structured light with orbital angular momentum, directly to a free space, or via light coupling; or, as shown in fig. 3, the laser light source 1 includes a laser 11 and a spatial modulation mechanism 12, and the structured light with orbital angular momentum is formed by a gaussian laser beam emitted by the laser 11 after passing through the spatial modulation mechanism 12. The laser 11 may be a semiconductor laser.

The structured light emitted by the laser light source 1 is continuous laser light, and can also be real pulse laser light. The wavelength range of the structured light is 380nm to 3800nm, and the power range of the structured light is 10uW to 100 mW.

Furthermore, as shown in fig. 4, the laser light source 1 includes a spatial phase plate array 13 and a plurality of lasers 11, wherein gaussian laser beams emitted by all the lasers 11 form a gaussian laser beam array, and the gaussian laser beam array forms structured light with orbital angular momentum in array distribution after passing through the spatial phase plate array 13. The laser 11 may be a semiconductor laser or other lasers.

In some embodiments, the spatial modulation mechanism 12 comprises a spatial phase plate or a spatial light modulator. The Gaussian laser beam without orbital angular momentum is modulated into the structured light with orbital angular momentum under the action of the spatial phase plate or the air-conditioning light modulator, so that the cells are regulated, and the air-conditioning modulation mechanism can regulate the direction of the orbital angular momentum of the structured light according to actual requirements, so that the cells are reliably regulated.

In some embodiments, 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 a fiber lens head, and the structured light with orbital angular momentum is coupled into the optical fiber from the light source, and is coupled onto the cell to be regulated after being focused by the fiber lens head.

Specifically, the gaussian beams output by the laser 11 are respectively coupled into optical fibers, and then the optical fibers are arranged into an array to output a gaussian beam array; processing one side of one glass or other transparent substrate half corresponding to one spiral phase plate array by using a micro-nano processing technology, and processing a corresponding micro-lens array by using a MEMs technology; the gaussian beam fiber array is aligned with the spiral phase plate array, with each microlens in the microlens array aligned with the following coupling fiber and the coupling fiber end face at the focal point of the corresponding lens 22. The gaussian laser beam output by each fiber is then converted into structured light with orbital angular momentum by the helical phase plate and coupled into the corresponding output fiber by the lens 22. Each optical fiber in the coupling optical fiber array outputs structured light with orbital angular momentum, so that the structured light array is realized. The structured light output by each optical fiber can regulate and control one cell in the cell culture microwell, and large-scale regulation and control are realized.

Or, the optical fiber is stretched to form a gradient optical fiber, and the diameter range of the emergent end of the gradient optical fiber is 500nm to 2 um. The light beam with orbital angular momentum is coupled to one end of the optical fiber, the other end of the optical fiber is corroded to form an optical fiber lens or a belt coating layer after the coating layer is removed, the optical fiber lens or the belt coating layer is stretched at high temperature to form the gradient optical fiber, the core diameter of the gradient optical fiber is changed into a range from 500nm to 2um after several millimeters from the original 8um to 10um, and the gradient optical fiber has a focusing function. The coupled structure light with orbital angular momentum can be focused on the cell to be regulated by the gradual change of the optical fiber after the focusing lens 22 on the optical fiber. In the case of a graded optical fiber, the tip of the fiber can be inserted into a cell under the cooperation of a microscope and a machine, and the structured light is directly applied to a cell nucleus.

As shown in fig. 5, the transmission fiber includes a fiber core 211 for transmitting a light beam, and a fiber cladding 212 is disposed around the outside of the fiber core 211; the fiber core 211 and the fiber cladding 212 may here be made of any suitable material having a small absorption coefficient, for example for light beams in the wavelength range 193nm-2 um. The optical fiber core 211 may be made of a doped silica material, preferably, the optical fiber core 211 is made of CaF2 or doped CaF2, and the optical fiber cladding 212 may be made of an undoped silica material, preferably, the optical fiber cladding 212 is made of silica or CaF 2.

A lens structure 213 is disposed outside the exit end of the fiber cladding 212, the lens structure 213 may have an arc-shaped convex structure, a focal plane 214 is disposed outside the lens structure 213, and the lens structure 213 is configured to enable the exposure laser to form a gaussian beam spot of a highly focused lithography 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 fiber exposure; specifically, the lens structure 213 may be a fiber lens formed on the end surface of the fiber core 211 by using a chemical etching method, or may be a super-surface lens 22 formed on the end surface of the fiber cladding 212 by using a micro-nano processing technique, for example.

As shown in fig. 6, as another embodiment, the optical channel device 2 includes a hollow probe 24, an optical channel is formed in the hollow probe 24, and a high optical medium layer is disposed on an inner wall of the optical channel; or the inside of the optical channel is filled with a regulating solution or a culture solution.

Specifically, the light tunnel device 2 is a hollow scanning probe microscope, and the hollow probe 24 can pierce the cell membrane and the cell nucleus under the cooperation of the microscope and the control software to directly enter the cell nucleus. The structural light beam or the light pulse with orbital angular momentum is coupled to the probe channel and directly transmitted into the cell nucleus to realize the regulation and control of the cell.

Preferably, the material of the high-gloss dielectric layer comprises at least one of SiO2 or CaF 2.

In some embodiments, the light tunnel device 2 comprises at least two lenses 22, and the structured light with orbital angular momentum is coupled to the cell after passing through all the lenses 22 in sequence. Wherein the last lens 22 is the objective of the microscope, which objective is capable of optically coupling the structure with orbital angular momentum to the cell.

In some embodiments, the culture device 3 includes a temperature adjustment mechanism, a culture solution for culturing cells is provided in the culture device 3, and the temperature adjustment mechanism can adjust the temperature of the culture solution; the culture device 3 includes an atmosphere adjustment mechanism capable of adjusting the atmosphere at the cells. The culture apparatus 3 is used to provide a suitable temperature and/or gas atmosphere for the culture of the cells. In particular, the temperature regulating mechanism is capable of regulating the culture fluid of the cells, wherein the culture fluid is capable of being refreshed. The atmosphere control mechanism can maintain the cells in a 5% mixture of carbon dioxide and air, etc.

More specifically, the culture device 3 further comprises a microscope for monitoring and observing the production and regulation of the cells.

Preferably, the cells can be cultured in a culture dish with wound through, and can also be cultured in a microfluidic flow channel.

The foregoing description is only exemplary of the preferred embodiments of the disclosure and is illustrative of the principles of the technology employed. It will be appreciated by those skilled in the art that the scope of the disclosure herein is not limited to the particular combination of features described above, but also encompasses other embodiments in which any combination of the features described above or their equivalents does not depart from the spirit of the disclosure. For example, the above features and the technical features disclosed in the present disclosure (but not limited to) having similar functions are replaced with each other to form the technical solution.

Further, while operations are depicted in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order. Under certain circumstances, multitasking and parallel processing may be advantageous. Likewise, while several specific implementation details are included in the above discussion, these should not be construed as limitations on the scope of the disclosure. Certain features that are described in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination.

Although the subject matter has been described in language specific to structural features and/or methodological acts, it is to be understood that the subject matter defined in the appended claims is not necessarily limited to the specific features or acts described above. Rather, the specific features and acts described above are disclosed as example forms of implementing the claims.

While the present disclosure has been described in detail with reference to the embodiments, the present disclosure is not limited to the specific embodiments, and those skilled in the art can make various modifications and alterations based on the concept of the present disclosure, and the modifications and alterations should fall within the scope of the present disclosure as claimed.

Claims

1. A cell regulation and control device is characterized by comprising a laser light source, an optical channel device and a culture device, wherein a cell to be regulated and controlled is arranged in the culture device, and structured light with orbital angular momentum emitted by the laser light source is coupled to the cell through the optical channel device to excite DNA in the cell.

2. The cell conditioning apparatus according to claim 1, wherein the laser light source comprises a laser that emits the structured light having orbital angular momentum; or, the laser light source comprises a laser and a spatial modulation mechanism, and the structured light with orbital angular momentum is formed by a gaussian laser beam emitted by the laser after passing through the spatial modulation mechanism.

3. The cell conditioning device according to claim 1, wherein the laser light source comprises a spatial phase plate array and a plurality of lasers, and the Gaussian laser beams emitted by all the lasers form a Gaussian laser beam array which passes through the spatial phase plate array to form structured light with orbital angular momentum distributed in an array.

4. The cell conditioning apparatus of claim 2, wherein the spatial modulation mechanism comprises a spatial phase plate or a spatial light modulator.

5. The cell conditioning apparatus according to claim 1, wherein the optical channel device comprises a single-mode or multi-mode optical fiber, and an exit end of the optical fiber is provided with a fiber lens head; or, the optical fiber is stretched to form a gradient optical fiber, and the diameter range of the emergent end of the gradient optical fiber is 500nm to 2 um.

6. The cell conditioning device according to claim 1, wherein the optical channel means comprises a hollow probe, an optical channel is formed in the hollow probe, and a high optical medium layer is arranged on the inner wall of the optical channel; or the inside of the optical channel is filled with a regulating solution or a culture solution.

7. The cell conditioning device according to claim 6, wherein the material of the high optical medium layer comprises at least one of SiO2 or CaF 2.

8. The cell conditioning device according to claim 1, wherein the light channeling device comprises at least two lenses, and the structured light with orbital angular momentum is coupled to the cell after passing through all the lenses in sequence.

9. The cell conditioning apparatus according to claim 1, wherein the culture device includes a temperature adjusting mechanism, a culture solution for culturing the cells is provided in the culture device, and the temperature adjusting mechanism is capable of adjusting the temperature of the culture solution; the culture device includes an atmosphere adjustment mechanism capable of adjusting an atmosphere at the cell.

10. The cell conditioning device according to claim 1, wherein the laser light source emits the structured light having a wavelength ranging from 380nm to 3800nm and a power ranging from 10uW to 100 mW.