A novel cascaded optical tweezer trapping device and method

Abstract

The present disclosure provides a cell manipulation device and method. The cell manipulation device includes: a light source module for providing a laser light source; a microcavity cascaded optical tweezer including a fiber optic probe and a microcavity optical waveguide that are nested and inserted. One end of the fiber optic probe is connected to the light source module for transmitting the laser light source, and the other end is nested and inserted with the microcavity optical waveguide. The microcavity optical waveguide is provided with an opening for cell circulation and a hollow cavity, and the microcavity cascaded optical tweezer is configured to capture the cells in the sample solution into the hollow cavity of the microcavity optical waveguide through the opening at least based on the capillary force formed at the nested insertion and the optical force formed by the laser light source, and is configured to be able to perform at least one cell manipulation.

Description

Technical Field

[0001] The present disclosure relates to the field of optical tweezer capture and manipulation, and in particular to a novel cascaded optical tweezer capture device and method. Background Art

[0002] Optical tweezers utilize the interaction between light and an object to achieve high-precision, high-resolution, and non-contact capture and manipulation of dielectric micro-particles, cells, and single molecules, and have achieved groundbreaking results in the application in the field of life science, promoting the development of biophysics. With higher requirements for optical tweezer technology in fields such as cell analysis, tumor cell detection, and cancer treatment, especially in the research and development of new drugs based on the physical characteristics detection of living cells, new challenges have been posed to the multi-functional manipulation ability of optical tweezer technology. Therefore, it is of great significance to carry out the research on multi-functional integrated microcavity cascaded optical tweezers.

[0003] Most of the existing methods focus on cell manipulation for a single cell sorting task. For example, as shown in the public document "Optical separation and controllable delivery of cells from particle and cell mixture", taking a tapered micro-nano fiber probe as an example, the sorting and delivery of cells and micro-particles of different sizes are carried out. However, while this method realizes the separation of micro-particles, the sorted micro-particles still exist at adjacent positions in the same sample pool and are easily interfered by the environment and cause secondary confusion, that is, true micro-particle separation is not achieved. Another example is as shown in the public document "Multifunctional single-fiber optical tweezers for particle trapping and transport", taking a planar fiber tip as an example, a 980nm laser source and a 650nm laser source are used to respectively excite linearly polarized laser beams to achieve the capture and collection of micro-particles. However, this method can only perform the capture and transport of a single micro-particle at a time, and the capture and delivery of the next micro-particle can only be carried out after the micro-particle is transported to the destination, with extremely low efficiency. As shown in the public disclosure of "Micro-nano particle manipulator based on capillary fiber", a variety of optical fibers are spliced, and the capture and collection of cells are achieved by frequently switching wavelengths. However, this method has a relatively complex preparation method while realizing relatively single functions, and frequent replacement of the laser wavelength is likely to cause damage to cells. The existing multi-functional optical tweezer technology has not been able to achieve the integration of various cell operation functions. Usually, it is necessary to combine cell detection systems based on multiple principles, and even rely on the cyclic switching of multiple non-optical tools to meet the requirements of high-throughput and high-precision cell manipulation, but this is likely to cause problems such as cell apoptosis and low efficiency. Summary of the Invention

[0004] The present disclosure provides a cell manipulation device and method capable of simultaneously performing multiple cell operations, which has the characteristics of simple structure and diverse functions.

[0005] According to a first aspect of the present disclosure, a novel cascaded optical tweezer capture device is provided, including:

[0006] A light source module for providing a laser light source;

[0007] A microcavity cascaded optical tweezer, including a fiber optic probe and a microcavity optical waveguide nested and inserted; wherein one end of the fiber optic probe is connected to the light source module for transmitting the laser light source, and the other end is nested and inserted with the microcavity optical waveguide;

[0008] The microcavity optical waveguide is provided with an opening and a hollow cavity for cell circulation, and the microcavity cascaded optical tweezer is configured to capture the cells in the sample solution into the hollow cavity of the microcavity optical waveguide through the opening at least based on the capillary force formed at the nested insertion part and the optical force formed by the laser light source, and is configured to be able to perform at least one cell manipulation.

[0009] In some possible implementation manners, the manipulation performed on the cells includes at least one of cell capture, cell transportation, cell sorting, and cell array arrangement.

[0010] In some possible implementation manners, the light source module is further configured to set parameters of the laser light source of the light source module;

[0011] And, the light source module is further configured to set the parameters of the laser light source to meet a first condition when the manipulation is high-throughput cell capture;

[0012] The first condition includes that the laser light source forms at least one focal point in the microcavity optical waveguide, and the resultant force of the capillary force and the optical force at the focal point adjacent to the opening points in the direction of the microcavity optical waveguide axially.

[0013] In some possible implementation manners, the light source module is further configured to enhance or reduce the power of the laser light source under the first condition when the manipulation is cell transportation.

[0014] In some possible implementation manners, the light source module is further configured to adjust the parameters of the laser light source to meet a second condition when the manipulation is cell sorting, and the target cells are sorted into the microcavity optical waveguide under the second condition;

[0015] Under the second condition, based on the refractive index and radius values of the target cells, the resultant force of the capillary force and the optical force received by the target cells points in the direction of the microcavity optical waveguide axially.

[0016] In some possible embodiments, the device further includes a polarization controller, which is connected between the light source module and the microcavity cascaded optical tweezers and is used to perform polarization processing on the laser light source to generate a polarized light source;

[0017] When the polarized light source satisfies the third condition, the cells rotate around the transverse axis of the microcavity optical waveguide in the microcavity optical waveguide.

[0018] In some possible embodiments, the light source module is further configured to adjust the parameters of the laser light source to satisfy the fourth condition when manipulating an array arrangement of cells;

[0019] Under the fourth condition, the captured cells are arranged in an array in the microcavity optical waveguide;

[0020] Wherein, the fourth condition includes: the light source transmitted to the optical fiber probe includes multiple columns of split light beams, and at least two columns of split light beams satisfy the first condition, correspondingly forming at least two columns of cell arrangements.

[0021] In some possible embodiments, the device further includes: a display module disposed above the microcavity cascaded optical tweezers, configured to display in real time images of the microcavity cascaded optical tweezers capturing and manipulating cells.

[0022] In some possible embodiments, the opening is in a shape of narrowing towards both sides of the hollow cavity.

[0023] According to a second aspect of the present disclosure, there is provided a novel cascaded optical tweezers capturing method, which is applied to the cell manipulation device described in any one of the first aspects, and the method includes:

[0024] Set the laser light source based on the cell manipulation method;

[0025] Transmit the laser light source through the optical fiber probe, and form an optical force for manipulating cells in the microcavity optical waveguide based on the laser light source, wherein the optical fiber probe and the microcavity optical waveguide are nested and inserted to form a microcavity cascaded optical tweezers; wherein one end of the optical fiber probe is connected to the light source module for transmitting the laser light source, and the other end is nested and inserted with the microcavity optical waveguide;

[0026] The microcavity optical waveguide is provided with an opening and a hollow cavity for cell circulation, and the microcavity cascaded optical tweezers are configured to capture the cells in the sample solution into the hollow cavity of the microcavity optical waveguide through the opening at least based on the capillary force formed at the nested insertion position and the optical force formed by the laser light source, and are configured to be able to perform at least one type of cell manipulation.

[0027] A novel cascaded optical tweezer trapping device and method provided by an embodiment of the present disclosure break through the limitations of traditional optical tweezers. By adjusting the parameters of the microcavity cascaded optical tweezer system, batch manipulation of cells can be achieved in the same microcavity cascaded optical tweezer system. It effectively solves the problems of traditional optical tweezers, such as single function during manipulation, inability to process in batches, and difficulty in integrating multifunctional operations. The device and method provided by the embodiments of the present disclosure can meet the high-throughput, large-scale, and automated requirements for the manipulation of micro-nano particles such as live cells and drug particles in current biomedical research and pharmaceutical development.

[0028] It should be understood that the above general description and the following detailed description are only exemplary and explanatory, and do not limit the present disclosure.

[0029] According to the following detailed description of exemplary embodiments with reference to the accompanying drawings, other features and aspects of the present disclosure will become clear. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The accompanying drawings herein are incorporated into the specification and constitute a part of this specification. These drawings show embodiments consistent with the present disclosure and, together with the specification, are used to explain the technical solutions of the present disclosure.

[0031] Figure 1 Schematic structural diagram of the cell manipulation device for the embodiment of the present disclosure;

[0032] Figure 2 Schematic diagram of the focus of the microcavity cascaded optical tweezer according to the embodiment of the present disclosure;

[0033] Figure 3 Schematic diagram of the result of cell sorting in the disclosed embodiment;

[0034] Figure 4 Schematic diagram of the result of capturing and directionally transporting cells in the embodiment of the present disclosure;

[0035] Figure 5 Schematic structural diagram of the cell manipulation device for the embodiment of the present disclosure;

[0036] Figure 6 Schematic diagram of the cell manipulation for cell rotation in the embodiment of the present disclosure;

[0037] Figure 7 Schematic structural diagram of the misaligned mode fusion splicing of the optical fiber probe for the embodiment of the present disclosure;

[0038] Figure 8 Schematic diagram of the misaligned mode distance and beam mode ratio according to the embodiment of the present disclosure

[0039] Figure 9 LP in the embodiment of the present disclosure 01 -LP 22 Schematic diagrams of four mode beams;

[0040] Figure 10 This is a schematic structural diagram of the stepper motor device for preparing the fiber optic probe and the microcavity optical waveguide in the embodiments of the present disclosure;

[0041] Figure 11 This is a schematic structural diagram of the fiber optic probe prepared in the embodiments of the present disclosure;

[0042] Figure 12 This is a schematic structural diagram of the microcavity optical waveguide prepared in the embodiments of the present disclosure;

[0043] Figure 13 This is a schematic structural diagram of the novel microcavity cascaded optical tweezer device in the embodiments of the present disclosure Detailed implementation manners

[0044] Various exemplary embodiments, features, and aspects of the present disclosure will be described in detail below with reference to the accompanying drawings. The same reference numerals in the drawings denote elements having the same or similar functions. Although various aspects of the embodiments are shown in the drawings, the drawings are not necessarily drawn to scale unless otherwise specified.

[0045] The special term "exemplary" herein means "serving as an example, embodiment, or illustrative". Any embodiment described as "exemplary" herein is not necessarily to be construed as superior to or better than other embodiments.

[0046] The term "and / or" in this document merely describes the associated relationship of the associated objects, indicating that there can be three relationships. For example, A and / or B can represent: A exists alone, A and B exist simultaneously, and B exists alone. In addition, the term "at least one" in this document means any one of a plurality or any combination of at least two of a plurality. For example, including at least one of A, B, and C can represent including any one or more elements selected from the set composed of A, B, and C.

[0047] In addition, in order to better illustrate the present disclosure, numerous specific details are given in the following detailed implementation manners. Those skilled in the art should understand that the present disclosure can be implemented without some specific details. In some instances, methods, means, elements, and circuits well-known to those skilled in the art are not described in detail so as to highlight the gist of the present disclosure.

[0048] The cell manipulation method provided by the present disclosure can be executed by a terminal device, a server, or other processing devices. Among them, the terminal device can be a user equipment (UE), a mobile device, a user terminal, a cellular phone, a cordless phone, a personal digital assistant (PDA), a handheld device, a computing device, a vehicle-mounted device, a wearable device, etc. In some possible implementation manners, the cell manipulation method can be implemented by a processor calling computer-readable instructions stored in a memory.

[0049] It can be understood that, without violating the principle logic, the above-mentioned various method embodiments mentioned in the present disclosure can be combined with each other to form combined embodiments. Due to space limitations, the present disclosure will not elaborate further.

[0050] As Figure 1 shown, it is a schematic structural diagram of a cell manipulation device according to an embodiment of the present disclosure. The cell manipulation device includes: a light source module 100 and a microcavity cascaded optical tweezer 200. Among them, the light source module 100 is used to provide a laser light source. The light source module 100 in the embodiment of the present disclosure may include a laser that can emit a monochromatic light laser beam with a preset wavelength and a laser driving unit that can adjust the working parameters of the laser. The laser driving unit can control the working parameters of the laser, such as parameters such as the output power and wavelength of the laser. In the embodiment of the present disclosure, the range of the light source power emitted by the laser can be 0-25 mW, and the preset wavelength can be 980 nm or 1550 nm. The above limitation on the light source module is only an exemplary embodiment, and in other embodiments, it can be a laser light source that can emit other types or other wavelengths.

[0051] In addition, the microcavity cascaded optical tweezer 200 can be connected to the light source module 100, used to receive the transmitted laser light source, and the other end extends into the sample solution. The microcavity cascaded optical tweezer 200 can capture cells in the sample solution into it at least according to the optical force of the laser light source, and can perform various cell manipulations. The sample solution in the embodiment of the present disclosure can be a sample liquid containing cells to be manipulated. For example, the sample solution may include yeast cells 501, chlorella cells 502, polystyrene cells 503, etc., but it is not a specific limitation of the present disclosure. Those skilled in the art can configure different sample solutions according to needs and manipulate the corresponding cells.

[0052] In addition, an embodiment of the present disclosure may further include a glass slide 600 for placing the microcavity cascaded optical tweezer 200. The microcavity cascaded optical tweezer 200 and the sample solution 500 are placed above the glass slide 600, and the microcavity cascaded optical tweezer 200 is in the sample solution 500. Among them, the semicircular arc surface represents the outer surface of the sample solution. In addition, in an embodiment of the present disclosure, a cover glass (not shown in the figure) may be provided on the sample solution and the microcavity cascaded optical tweezer 200. To prevent the glass slide from observing the cells in the microcavity cascaded optical tweezer 200, an embodiment of the present disclosure may further provide a through hole at a position corresponding to the microcavity cascaded optical tweezer 200 on the cover glass. The through hole can be used to observe the cell condition and is also convenient for the display module provided in other embodiments to obtain a display image.

[0053] To observe the characteristic information of the captured and manipulated cells, an embodiment of the present disclosure further includes a display module, and the display module may include a microscope 300. The microscope 300 can be installed above the microcavity cascaded optical tweezer 200 to observe the manipulated cells by adjusting the magnification. Alternatively, the microscope 300 can be arranged above the through hole to facilitate image acquisition. Preferably, an embodiment of the present disclosure further includes a display 400, and the display 400 is communicatively connected to the microscope 300. The captured image in the microscope 300 can be transmitted to the display 400 for real-time display, thereby further facilitating the observation of the cells. Alternatively, in a preferred embodiment, the collected images can also be stored using a memory and transmitted to other electronic devices using a communication module. The memory may include a local storage device and a cloud server device, and the communication module may include a wifi module, a Bluetooth module, or other network connection devices.

[0054] Further, a moving platform 700, such as a three-dimensional moving stage, may be provided below the microcavity cascaded optical tweezer 200. By controlling the movement of the moving platform, the observed area can be adjusted to facilitate selecting a suitable observation area for image capture. The moving platform may include a first moving platform disposed under the optical fiber probe and a second moving platform disposed under the glass slide, so as to realize the separate movement control of these two parts of the structure.

[0055] In addition, the microcavity cascaded optical tweezer according to an embodiment of the present disclosure may include a fiber probe 201 and a microcavity optical waveguide 202 that are nested and inserted. Among them, the types of fiber probes include, but are not limited to, single-mode fibers, and the materials of the microcavity optical waveguides include, but are not limited to, silica materials that are the same as those of single-mode fibers. The fiber probe 201 is prepared from an optical fiber. One end of the fiber probe is connected to the light source module for transmitting the laser light source, and the other end has a needle-like structure and is nested and inserted with the microcavity optical waveguide. The microcavity optical waveguide 202 is configured as a hollow tubular structure with openings at both ends. One opening is used for nested insertion with the fiber probe, and the other opening is used for cell circulation, and has a hollow cavity to form a microcavity optical waveguide for trapping cells. Among them, the material of the microcavity optical waveguide 202 may be high-purity step-type quartz glass (not specifically limited in the present disclosure), and its tube diameter size remains consistent. The opening for cell circulation is in a converging shape with respect to both sides of the hollow cavity. In the embodiment of the present disclosure, based on the nested insertion, the microcavity cascaded optical tweezer forms a semi-channel structure that enables cell circulation, and there is a slit at the nested insertion of the microcavity optical waveguide and the micro-nano fiber probe due to the non-complete smoothness of its surface.

[0056] In the embodiment of the present disclosure, the tip diameter of the micro-nano fiber probe ranges from 15 to 25 μm, the tube diameter of the microcavity optical waveguide ranges from 15 to 26 μm, the slit formed by the nested insertion of the microcavity optical waveguide and the micro-nano fiber is 0 to 1 μm, the length of the hollow cavity is 50 to 200 μm, and the diameter of the port of the hollow cavity (the opening for cell circulation) ranges from 10 to 20 μm. The above is only an exemplary illustration of the present disclosure and does not constitute a specific limitation of the present disclosure.

[0057] In addition, based on the nested insertion, the microcavity cascaded optical tweezer is configured to capture the cell into the hollow cavity of the microcavity optical waveguide through the opening at least based on the capillary force formed at the nested insertion and the optical force formed by the laser light source. Specifically, the slit formed by the combination of the microcavity optical waveguide 202 and the micro-nano fiber probe 201 will generate a capillary phenomenon, which will generate a capillary force on the cell when acting on the cell, and the magnitude is 0 to 20 pN. This capillary force can act on the cells in the sample solution, especially the cells located at the opening of the microcavity optical waveguide, and capture them into the hollow cavity through the opening.

[0058] Determine the capillary force of the microcavity cascaded optical tweezer according to the moving speed of the cell in the microcavity optical waveguide. The capillary force F D Can be expressed as:

[0059]

[0060] In the formula, τ p Particle velocity response time, m p Is the particle mass, u is the fluid velocity, v is the particle velocity, d cis the particle diameter, and ρ c is the particle density. The particles in the embodiments of the present disclosure may include cells in a sample solution.

[0061] In addition, Figure 2 is a schematic diagram of the focus of the microcavity cascaded optical tweezers according to an embodiment of the present disclosure. The microcavity optical waveguide 202 structure in the embodiments of the present disclosure is a symmetric cylinder with a single-layer medium, having an annular waveguide layer and a central air hole, forming a hollow cavity. Along the radial direction of the microcavity optical waveguide, the refractive index distribution of its waveguide layer is relatively high, and the air core in the middle changes with the refractive index of the surrounding medium. According to the refractive index distribution relationship of the microcavity cascaded optical tweezers, the laser beam is transmitted from the optical fiber to the tip of the microcavity optical waveguide and undergoes multiple reflections and refractions on the wall of the microcavity optical waveguide within the microcavity optical waveguide. According to the law of refraction:

[0062] sin(θ1) = n2sin(θ2)

[0063] sin(θ2) = n1sin(θ3)

[0064] In the formula, θ1 is the initial incident angle of the laser beam, θ2 is the reflection angle of the laser beam, θ3 is the refraction angle of the laser beam, n1 is the refractive index of the side wall of the microcavity cascaded optical tweezers, and n2 is the refractive index of the sample solution. For example, the refractive index of yeast cells in the sample solution is 1.39, the refractive index of polystyrene cells is 1.59, and the refractive index of chlorella cells is 1.5. Each time the light from the laser source undergoes reflection and refraction, new reflection and refraction angles will be formed. Subsequently, when the light undergoes multiple reflections and refractions inside the hollow cavity and on the side wall and reaches the same position, the wave crests and wave troughs of the light beam will overlap, generating enhanced interference and forming a strong light spot, that is, the focus. Based on the above rules, multiple foci are finally formed inside and at the port of the microcavity cascaded optical tweezers. At this time, the path length L of the light needs to satisfy the formula:

[0065] L = mλ

[0066] In the formula, L is the path length of the light, m is an integer, and λ is the wavelength of the light.

[0067] For example, when the wavelength λ of the light is 980 nm, if the total path length L of the light after multiple reflections and refractions in the microcavity optical waveguide is exactly 1960 nm, that is, m = 2; this means that the total path length of the light passing through the microcavity is 2 times the wavelength λ (m = 2), so in this case, the light will form a focus inside the microcavity. The light intensity at the focus is stronger than that in other regions, and the light intensity of the focus farther away from the optical fiber probe will gradually weaken ( Figure 2The circled part is the focus). Therefore, when the optical force formed by the focus closest to the opening for cell capture is greater, it is easier to capture cells, and the cells can be captured into the microcavity optical waveguide or captured around the opening. Furthermore, by combining the capillary force in the microcavity optical waveguide and the optical force of other foci, the cells can be further smoothly captured into the optical waveguide. In the embodiments of the present disclosure, in order to form at least one focus in the hollow cavity of the microcavity optical waveguide, the length of the hollow cavity should be greater than the wavelength of the laser light source.

[0068] Through the above process, the laser light source reflects and refracts multiple times with the side walls in the microcavity optical waveguide, converges inside and at the port thereof, and forms multiple foci. Since the energy of the laser beam light is absorbed by the sample solution during propagation and converted into heat energy or other forms of energy, the energy of the laser beam gradually decreases from the micro-nano fiber probe to the port of the microcavity cascaded optical tweezer during propagation. When the cells at the port of the microcavity cascaded optical tweezer move inward, affected by the multiple foci, the cells can be trapped on the optical axis and move along the optical axis into the microcavity optical waveguide. Based on the above principle, high-throughput capture of cells in the sample solution can be achieved.

[0069] In the embodiments of the present disclosure, the parameters of the laser light source emitted by the light source module can also be adjusted to enhance or weaken the force for capturing cells inward, so as to achieve the capture and release of cells. For example, the power of the laser light source can be increased to enhance the force for capturing cells inward, or the power of the laser light source can be decreased to weaken the force for capturing cells inward, so as to achieve the release of cells.

[0070] The above method of adjusting the parameters of the laser light source of the light source module can be manual or intelligent control. The light source module can receive the set light source parameters input through the input device and generate the corresponding laser light source according to the received parameters. The input device can include input devices such as a keyboard, a touchpad, and a touch screen that can receive the light source parameters. Or the light source module can also be connected to the control module, receive the control signal, and adaptively adjust the light source parameters according to the control signal. The control device is configured to generate the corresponding control signal according to the type of cell manipulation to achieve parameter adjustment under different manipulation tasks. Among them, each manipulation type can be correspondingly configured with a corresponding control signal, and the control signal can include the parameter value or range of the light source parameters. In the embodiments of the present disclosure, the control module can be integrated in the light source module or independent of the light source module. In the embodiments of the present disclosure, the case where the control module is integrated in the light source module is taken as an example for description, but it is not a specific limitation of the present disclosure.

[0071] In some embodiments, the light source module 100 is further configured to set parameters of the laser light source of the light source module; the light source module is further configured to, when the operation is for high-throughput cell capture, set the parameters of the laser light source to meet a first condition; the first condition includes that the laser light source forms at least one focal point in the microcavity optical waveguide, and the resultant force direction of the capillary force and the optical force at the focal point adjacent to the opening points into the microcavity optical waveguide.

[0072] As described in the above embodiments, when the resultant force direction of the capillary force and the optical force at the focal point adjacent (closest) to the opening for cell flow points into the microcavity optical waveguide, the resultant force of the remaining focal points will surely point into the microcavity optical waveguide. In this case, cell capture can be achieved. Figure 1 It can be understood as a schematic diagram of a microcavity cascaded optical tweezer high-throughput capture device in the embodiments of the present disclosure.

[0073] In the embodiments of the present disclosure, the optical force formed by the laser light source includes a gradient force F g and a scattering force F s . Among them, the scattering force F s is an outward optical force, and the gradient force F g is an inward optical force. The gradient force F g is the force exerted on the electric dipole moment in the particle in a non-uniform electromagnetic field, which is proportional to the square of the optical intensity gradient and points to the maximum of the optical field intensity, causing the particle or cell to be pulled towards the port of the microcavity cascaded optical tweezer; the laser beam obtains the scattering force F s during the scattering process by exchanging momentum with photons, and its direction is along the propagation direction of the laser beam, pushing the particle away from the port of the microcavity cascaded optical tweezer.

[0074] When the resultant force of the gradient force, the scattering force and the capillary force inside the microcavity cascaded optical tweezer points into the microcavity optical waveguide, a capture force for cells can be formed. This capture force is closely related to factors such as the wavelength of light, the properties of the particles, and the particle size. The distribution and change of the vector optical field are accurately described by solving the Maxwell equations. Among them, the total optical force F received by the particle is:

[0075] F = ∮ S (<T M > · n)dS

[0076] where the integration is performed on the closed surface S around the cell, n is the surface normal vector, and <T M > is the Maxwell stress tensor independent of time. The expression of the Maxwell stress tensor in vacuum is:

[0077]

[0078] where EE* and HH* are the outer products of the electric and magnetic fields, E is the electric field, H is the magnetic field, ε is the permittivity; μ is the permeability; I represents the unit binary number.

[0079] In addition, the light source module 100 can be configured to adjust the parameters of the laser light source to meet the second condition when the operation is cell sorting, and under the second condition, the target cells are sorted into the microcavity optical waveguide; wherein, under the second condition, based on the refractive index and radius value of the target cells, the resultant force of the capillary force and the optical force acting on the target cells in the axial direction points into the microcavity optical waveguide. Specifically, as Figure 3 shown, it is a schematic diagram of the result of realizing cell sorting in the disclosed embodiment.

[0080] That is to say, in the disclosed embodiment, by setting parameters such as the wavelength of the laser light speed, the magnitude of the optical force can be adjusted so that when the resultant force of the optical force and the capillary force acting on the target cells points into the cavity, the target cells are sucked into the microcavity optical waveguide; when the resultant force of the optical force and the capillary force points to the open end of the cavity, the target cells are pushed away from the cavity direction, thereby realizing cell sorting and transportation.

[0081] After the cells enter the microcavity optical waveguide, they are not only affected by the optical force reflected by the tip of the micro-nano fiber probe and the inner wall of the microcavity optical waveguide, but also affected by the capillary force generated by the microcavity cascaded optical tweezers. The gradient force and scattering force acting on the particles in the microcavity optical waveguide are respectively:

[0082]

[0083] where n2 is the refractive index of the medium around the cells. For example, when the medium is water, the refractive index is 1.33, δ is the electric dipole polarizability of the trapped particles, and the relationship between δ and the radius r of the cells is:

[0084]

[0085] where m = n s / n2, n2 represents the refractive index of the particles, and E is the polarization electric field strength inside the cells. The scattering force F s is:

[0086]

[0087] where, <s>is the time-domain averaged Poynting vector, and the scattering cross-section C s is:

[0088]

[0089] where When the scattering force on the cell is less than other resultant forces, the cell will be continuously captured into the microcavity. And due to the multi-focus effect, the cell moves along the optical axis in the microcavity optical waveguide from the port of the microcavity cascaded optical tweezers to the tip of the micro-nano optical fiber probe, thereby realizing the batch capture of microparticles.

[0090] To achieve the directional transportation of microparticles with different refractive indices in the cavity, the embodiments of the present disclosure propose a structural design capable of capturing and directionally transporting cells. Figure 4 This is a schematic diagram of the result of capturing and directionally transporting cells in the embodiments of the present disclosure. The embodiments of the present disclosure can adjust the working parameters of the laser, which can enhance the optical force acting on the microparticles, that is, the resultant force of the gradient force and the scattering force, and can also generate a thermophoretic force. This force can drive the microparticles to move from the high-temperature region to the low-temperature region, and its direction is away from the micro-nano optical fiber probe. The expression of the thermophoretic force is:

[0091]

[0092] where μ is the thermophoretic coefficient, is the temperature gradient.

[0093] According to this principle, by precisely adjusting the working parameters of the laser, the resultant force of the thermophoretic force, the optical force, and the capillary force on the cell is manifested as a pushing force pointing outside the microcavity optical waveguide. At this time, the cell will be effectively pushed away from the micro-nano optical fiber probe. Therefore, by using the microcavity cascaded optical tweezers technology, the batch directional transportation of microparticles can be efficiently realized.

[0094] In addition, due to the semi-closed structure of the microcavity cascaded optical tweezers microcavity optical waveguide, the cell is in a stable state of shielding external interference in the microcavity optical waveguide, which is beneficial to modulating the light to act on the cell alone for precise cell manipulation. Specifically, Figure 5 This is a schematic diagram of the structure of another cell manipulation device in the embodiments of the present disclosure. Wherein, the device further includes a polarization controller 800, which is connected between the light source module 100 and the microcavity cascaded optical tweezers 200 and is used for polarizing the laser light source to generate a polarized light source; when the polarized light source meets the third condition, the cell rotates around the transverse axis of the microcavity optical waveguide in the microcavity optical waveguide.

[0095] The laser light source will carry angular momentum and act on the cell in the polarized state. The embodiments of the present disclosure set the cell as a uniaxial microparticle. According to the electromagnetic field theory, the total angular momentum can be expressed as:

[0096] J = -ε0∫r × (E × B) dr 3

[0097] where E and B are the electric field strength vector and magnetic induction intensity vector of the light field respectively, r is the position coordinate vector, and ε0 is the permittivity. The spin angular momentum of the cell in the polarization state is:

[0098]

[0099] where ω represents the angular frequency in the plane wave. The incident light beam has both circular polarization components and linear polarization components, which is expressed as:

[0100] E = E0e icot (cosΦx + isinΦy)

[0101] where Φ is the ellipticity, Φ = 0 or π / 2 corresponds to linear polarization, and Φ = π / 4 corresponds to circular polarization. To calculate the change in angular momentum caused by the light source passing through the birefringent particles, considering that the optical axis of the uniaxial particle is in the xy plane, then

[0102] E = E0e iωt (cosΦc cosθ - isinΦsinθ)x′ + E0e iωt (cosΦsinθ + isinΦc cosθ)y′

[0103] where θ is the angle between the fast axis of the incident elliptically polarized light and the optical axis of the particle.

[0104] Due to the internal structure of the crystal, the light source has different propagation speeds and refractive indices in different directions. Therefore, the light beam is decomposed into an o-ray that propagates at a fixed refractive index and an e-ray whose refractive index depends on the propagation direction. Among them, the o-ray and e-ray are mutually orthogonal light beams. In the case of birefringent particles, the o-ray refers to the linearly polarized light perpendicular to the crystal optical axis after decomposition, and the e-ray refers to the linearly polarized light orthogonal to the polarization direction of the o-ray. The refractive indices of the particle for the o-ray and e-ray are n0 and n e . The phase difference Φ between the two lights when the light beam passes through is Φ = kd(n0 - n e ), where k represents the wave number of light propagation, which refers to the number of waves per unit length and is defined as k = 2π / λ, and λ represents the wavelength of light. d specifically refers to the thickness of the particle in the direction of the optical axis, that is, the distance that the light propagates in the particle along the optical axis direction. Then, integrating the above formula, according to the law of conservation of angular momentum, the torque per unit area on the particle is obtained as:

[0105]

[0106] The above formula shows that for linearly polarized light with Φ = 0 or π / 2, the torque τ will be proportional to sin2θ, there is an angular equilibrium position, and the particle will stop after moving in the corresponding direction. For circularly polarized light with Φ = π / 4, the torque is constant. Thus, the particle suspended in the liquid will produce continuous and constant rotation, and the torque reaches the maximum value when kd(n0 - n e ) = π.

[0107] That is to say, the third condition of the embodiment of the present disclosure includes: after the polarization controller performs polarization processing on the laser light source, the optical phase difference between the o light propagating with a fixed refractive index and the e light whose refractive index depends on the propagation direction generated by decomposing the obtained polarized light source is 0 or π / 2, and at this time, the cells in the cavity rotate and then stop. Alternatively, the third condition of the embodiment of the present disclosure includes: when the optical phase difference between the o light propagating with a fixed refractive index and the e light whose refractive index depends on the propagation direction generated by decomposing the polarized light source obtained after the polarization controller performs polarization processing on the laser light source is Φ = π / 4, the cells in the cavity will rotate continuously and constantly, that is, make a circular motion around the axis of the cavity.( Figure 6 Schematic diagram showing cell rotation according to an embodiment of the present disclosure)

[0108] The cell manipulation method provided by the embodiment of the present disclosure can capture cells only by using low power, preventing the generation of optical damage. At the same time, the optical tweezers of the embodiment of the present disclosure can provide a large enough torque while ensuring the cell viability, so as to realize particle rotation.

[0109] In addition, the embodiment of the present disclosure can also control the rotation speed of the cells by adjusting the power of the laser light source. For example, when the power is increased, the rotation speed increases, and when the power is decreased, the rotation speed decreases.

[0110] Figure 7 It is a schematic structural diagram of the cell manipulation in an array arrangement according to an embodiment of the present disclosure. Among them, the device of the embodiment of the present disclosure further includes a misaligned fusion spliced optical fiber, which is connected between the light source module and the microcavity cascaded optical tweezers. The misaligned fusion spliced optical fiber is configured to at least include a first optical fiber and a second optical fiber, and the first optical fiber and the second optical fiber are misaligned and connected. The misalignment distance in the embodiment of the present disclosure can be greater than 0 and less than the diameters of the first optical fiber and the second optical fiber, for example, it can be 5um. Among them, parameters such as the core radius and length of the first optical fiber can be different, but they are not specifically limited in the present disclosure.

[0111] The mode of light beam propagating in the optical fiber depends on the normalized frequency parameter V of the transmitted light wave in the optical fiber (the ratio of the cut-off frequency of the optical waveguide electromagnetic mode to the optical waveguide structure quantity of the optical fiber). Among them, the V value determines the number of beam modes allowed to be transmitted in the optical waveguide. The larger the V value, the more transmission modes. The calculation formula of the V value is as follows:

[0112]

[0113] where α is the core radius of the second optical fiber, λ is the incident wavelength, and n core is the core refractive index of the output optical fiber, and n cladding is the cladding refractive index of the output optical fiber.

[0114] In the embodiments of the present disclosure, when V is less than the first threshold, the split light beam formed by misaligned splicing includes a column of light beams; when V is greater than or equal to the first threshold and less than the second threshold, the split light beam formed by misaligned splicing includes two columns of light beams; when V is greater than or equal to the second threshold, the split light beam formed by misaligned splicing includes four columns of light beams; and when V is greater than the third threshold, the split light beam formed by misaligned splicing includes eight columns of light beams. Additionally, in the embodiments of the present disclosure, the misaligned splicing of optical fibers can also be used to adjust the light refraction angle of the received laser light source, thereby adjusting the proportion of different mode light beams in the total propagated light beam. Figure 8 It is a schematic diagram of the misalignment distance and the proportion of light beam modes according to the embodiments of the present disclosure. By setting different misalignment distances, the proportion of light beam modes can be adjusted.

[0115] In one embodiment, when V < 2.405, only the LP 01 mode light beam can propagate; when 2.405 ≤ V < 3.832, the LP 11 mode light beam (approximately two symmetric columns of light beams) is generated and propagates; when 3.832 ≤ V < 5.520, the LP 21 mode light beam appears in the optical fiber; when 5.520 ≤ V < 7.015, the LP 22 mode light beam is successfully excited. Figure 9 This is a schematic diagram of the LP 01 , LP 01 , LP 01 , LP 01 four mode light beams in the embodiments of the present disclosure. Among them, the region with higher brightness represents the region where the light beam is located.

[0116] Based on the above configuration, the light source module in the embodiments of the present disclosure is further configured to adjust the parameters of the laser light source to meet the fourth condition when the manipulation is in the form of a cell array arrangement. Under the fourth condition, the cells in the cavity are arranged in an array. The array arrangement may include multiple column arrays. Specifically, it includes at least two column arrays. When there are more than two column arrays, a three-dimensional array structure can be formed, that is, at least two column arrays are not in the same plane.

[0117] Specifically, in the embodiments of the present disclosure, by misaligned splicing of optical fibers, a light beam with at least two sub-beam modes that can coexist in a microcavity optical waveguide can be formed. Among them, parameters such as the wavelength of the laser light source, the core radius of the misaligned spliced optical fiber, and the cladding of the output optical fiber can be adjusted, and the corresponding V value can be set to determine the light beam mode input to the optical fiber probe. For example, in the embodiments of the present disclosure, LP 01 (a column of light beams, that is, the commonly used laser beam mode) and LP 21 (formed by the convergence of four columns of light beams with an approximately symmetric distribution, which can be approximated as a set of four LP 01 mode light beams distributed symmetrically in a cross shape) mode light beams can be formed.

[0118] In some embodiments, when cells enter the hollow cavity (microcavity optical waveguide), they will be affected by the force of the light beam formed by the propagating laser light source. Based on the principle of cell capture by the laser light source output from the single-mode optical fiber described in the above embodiments, in the case of generating at least two modes of sub-beams, the sub-beams can act on the cells, and then a plurality of focal points can be formed in the microcavity optical waveguide. Based on the arrangement of the focal points corresponding to each light source, a corresponding column of cell arrangements can be formed. Furthermore, for each light source, a corresponding column of cell arrangements can be formed, and finally, multiple columns of cell arrangements corresponding to multiple light sources can be formed. Taking one of the four columns of particles as an example, in the microcavity, the particles are mainly affected by the combined gradient force and scattering force of the LP 01 light beam and one of the four LP 21 light beams (approximately clamping the cells with two light beams). At the same time, due to the existence of capillary action in the microcavity, a certain liquid flow velocity will be induced, thereby exciting a capillary force on the particles. When the resultant force of the optical forces formed by the two-mode sub-beams is balanced with the capillary fluid force, the particles can be stably captured in the microcavity. The capture principle of a single particle in the four columns of particles is approximately the same as the first condition.

[0119] In one embodiment, a laser light source with a wavelength of 650 nm is used. By misaligned splicing a 650 nm wavelength optical fiber with a 1550 nm wavelength optical fiber, when the misalignment distance reaches 5 μm, the excited LP 01 mode light beam and LP 21 mode light beam reach the optimal state. At this time, if each light source satisfies the first condition (the total optical force is balanced with the capillary force), a three-dimensional array arrangement of cells in four columns can be achieved.

[0120] That is to say, in the case of the manipulation for cell array arrangement, the fourth condition that needs to be satisfied includes: the light source transmitted to the optical fiber probe includes multiple columns of sub-beams, and at least two columns of sub-beams satisfy the first condition described in the above embodiments. At this time, at least two columns of cell arrangements can be correspondingly formed.

[0121] In addition, the embodiments of the present disclosure also provide a preparation method for an optical fiber probe and a microcavity-level optical waveguide. Figure 10 Schematic diagram of the stepping motor structure for preparing the optical fiber probe and the microcavity optical waveguide in the embodiments of the present disclosure. Figure 11 Schematic diagram of the structure of the optical fiber probe prepared in the embodiments of the present disclosure.

[0122] In some possible implementation manners, the preparation method of the micro-nano optical fiber probe includes:

[0123] Using a stepping motor 900 and a micro-nano motion platform to control the movement of the optical fiber preform, so that the flame reciprocally scans and heats the optical fiber preform to a molten state, and then performs stretching; the stretching method includes the following steps:

[0124] 1) Fix one end of the optical fiber preform on the micro-nano motion platform and the other end on the stepping motor, set the initial position and moving speed of the stepping motor (for example, the initial position is at 50 mm and the speed is 5 mm / s), and use an alcohol lamp 1000 to heat and stretch the preform.

[0125] 2) When the stepping motor moves to the preset position, increase the moving speed (for example, the preset position is at 46 mm and the stepping motor speed is set to 20 mm / s), quickly stretch the preform until the preform is broken, forming a gradually changing tapered optical fiber structure, and this tapered optical fiber structure can be constructed as an optical fiber probe.

[0126] In addition, Figure 12 Schematic diagram of the structure of the microcavity optical waveguide prepared in the embodiments of the present disclosure. In some possible implementation manners, the preparation method of the microcavity optical waveguide includes:

[0127] 1) Using a stepping motor and a micro-nano motion platform to heat the microcavity optical waveguide preform with a flame to a molten state by reciprocally scanning, and then perform stretching in the following manner;

[0128] 2) Fix one end of the microcavity optical waveguide preform on the micro-nano motion platform and the other end on the stepping motor, set the initial position and moving speed of the stepping motor (for example, the initial position is at 50 mm and the speed is 100 mm / s), use an alcohol lamp 1 cm away from the flame to heat and quickly stretch the microcavity optical waveguide preform until the microtube is broken, forming a microcavity optical waveguide.

[0129] The shape of the microcavity optical waveguide port is prepared to have a necking structure. The necking can better focus the light beam, increase the light field distribution gradient, and is conducive to the precise manipulation of particles by light. Moreover, the necking can increase the flow rate of the liquid, which is conducive to the capture of particles. It can be understood that the selected necking structure in this experiment is for better manipulation of particles, and it is not the only choice for the shape of the microcavity optical waveguide port. In specific environments and requirements, various shapes such as a flat opening (i.e., no depression at the port) and a bent port can be selected.

[0130] In addition, the embodiments of the present disclosure can use a high-precision three-dimensional robotic arm to nest and plug the micro-nano optical fiber probe and the microcavity optical waveguide to form a semi-channel structure with a hollow interior, and construct a microcavity cascaded optical tweezer. Figure 13 It is a schematic structural diagram of the microcavity cascaded optical tweezer of the embodiments of the present disclosure. Among them, 301 represents the captured cell.

[0131] To better understand the multi-functional manipulation principle and process of the cell manipulation device provided by the embodiments of the present disclosure, an exemplary illustration is provided.

[0132] The embodiments of the present disclosure can control the light source module to emit a laser beam with a wavelength of 980 nm. The laser beam reaches the microcavity cascaded optical tweezer through the transmission optical fiber, and is reflected and refracted multiple times with the microcavity optical waveguide wall in the microcavity optical waveguide, and finally converges at the port of the microcavity cascaded optical tweezer to form a focal point. Among them, the microcavity cascaded optical tweezer is formed by nesting and docking the optical fiber probe and the microcavity optical waveguide. The microcavity optical waveguide constitutes a semi-channel structure with a hollow interior and communicates with the sample solution. When the cell captured at the opening of the microcavity cascaded optical tweezer moves into the microcavity optical waveguide, the focal point at the port of the microcavity cascaded optical tweezer can capture the cell in the sample solution. The particle moving into the microcavity optical waveguide is under the combined action of the optical force and the capillary force and moves towards the tip of the optical fiber probe until the optical force and the capillary force reach equilibrium, at which time the cell stops moving. And the focal point at the port of the microcavity cascaded optical tweezer can capture the next cell, thereby realizing the high-throughput capture of cells. In addition, by adjusting the output power of the light source module, the optical force on the particle is made less than the capillary force, and the particle is captured into the microcavity optical waveguide of the microcavity cascaded optical tweezer under the action of the capillary force, realizing the high-throughput capture of different types of particles.

[0133] On the other hand, when the light source module is activated and the wavelength is tuned to 1550 nm, the power of the laser is set between 50 - 100 mW. Since water has a relatively high absorption rate at this wavelength, after absorbing the laser with a wavelength of 1550 nm, the local temperature of the water will increase, thus forming a temperature difference. This temperature difference further generates a thermophoretic force, driving the microparticles to move from the high-temperature region to the low-temperature region. In addition, the higher the power of the laser, the greater the temperature gradient generated, and the corresponding thermophoretic force is also stronger. Therefore, under the combined action of optical force, thermophoretic force, and capillary microfluidic force, when the resultant force direction is consistent with the light propagation direction, the cells will continuously move towards the port of the microcavity cascaded optical tweezer, and finally achieve the directional transportation of cells.

[0134] When studying the influence of optical power on the capture of different kinds of microparticles by the microcavity cascaded optical tweezer, it is necessary to comprehensively consider the interaction between optical force and capillary force, and adjust the operating parameters of the laser. When the resultant force on the microparticles in the microcavity optical waveguide port and inside the microcavity optical waveguide is negative, that is, when the microparticles are mainly affected by the capillary force, the microparticles can be captured into the microcavity cascaded optical tweezer under the action of the capillary force, realizing the capture and collection of different kinds of particles.

[0135] In addition, adjust the output power of the microcavity cascaded optical tweezer system; set the capture force pointing inside the microcavity optical waveguide of the microcavity cascaded optical tweezer to be negative, and the pushing force along the light propagation direction to be positive. When microparticles with different refractive indices and absorption rates are at the port of the microcavity cascaded optical tweezer, when the resultant force on the microparticles is negative, they are sucked into the microcavity optical waveguide; when the resultant force on the microparticles is positive, they are pushed away from the port direction of the microcavity optical waveguide, realizing the precise sorting of microparticles with specific refractive indices and absorption rates.

[0136] By performing optical regulation on the output light of the laser; the laser beam output from the light source module enters the three-ring polarization controller 800 through a low-loss flange connection. Here, the three-ring polarization controller 800 serves as a polarization control unit. The diameters of the three rings of the three-ring polarization controller 800 are all 27 mm, and birefringence is induced by bending the optical fiber (when light propagates, due to different propagation speeds in two orthogonal directions, a fast axis and a slow axis are formed. The single light beam is actually the vector sum of the light components propagating along the fast axis and the slow axis, and the phase difference between the two directions of propagation forms polarization).

[0137] Winding a single-mode optical fiber around a ring will produce the effect of phase delay. According to the phase delay theory, in this device, 2 turns correspond to a phase delay of π / 2, and 3 turns correspond to a phase delay of π / 4. Therefore, the first ring in the three rings corresponds to a quarter-wave plate, which converts the polarization state of the input light into a linearly polarized state. The second ring corresponds to a half-wave plate, whose function is to rotate the linearly polarized light. The last quarter-wave plate can change the polarization state of the linearly polarized light into an arbitrary polarization state. To achieve a more precise control effect, slowly adjust the angle of the polarization ring. The optical fiber twists accordingly, and the change in the directions of the fast axis and slow axis in the optical fiber causes a change in the phase difference, realizing fine control of the polarization state according to the birefringence principle. Finally, pass the light through a quarter-wave plate and then through a polarizer. When rotating the polarizer and extinction occurs, it indicates that the outgoing light is circularly polarized light. Keeping the position of the three-ring polarization controller unchanged can obtain a stable output of circularly polarized light. Use the three-ring polarization controller to output stable circularly polarized light to the tip of the optical fiber. On the cross-section perpendicular to the optical axis where the cell is located, due to the combined action of the optical gradient force and the scattering force, the cell will not shift in position on the cross-section. The cell fixed in the three-dimensional space where the microcavity optical waveguide is located will undergo momentum transfer with the photons of the polarized light. Since the polarized light carries spin angular momentum and acts on the cell, a torque in the same direction as the angular momentum direction is generated on the cross-section perpendicular to the optical axis where the cell is captured by the light. Since the microcavity optical waveguide shields the interference caused by the normal flow of the liquid in the sample pool and the flow caused by evaporation in this direction, considering that Brownian motion and the gravity of the cell are much lower than the optical force, the cell will rotate uniformly along the polarization direction with the optical axis as the rotation axis.

[0138] In addition, by performing a 5-μm misaligned fusion splicing on the micro-nano optical fiber probe, an LP that can coexist in the microcavity optical waveguide can be formed. 01 and LP 21 mode beams. Since beams of different modes have different propagation constants, they respectively exhibit different focused light fields, that is, LP 01 and LP 21 respectively form two parts and four parts separated areas where two columns and four columns of beams converge. The split beams of the LP 01 mode and the LP 21 mode act on the cell particles, and multiple focal points can be formed in the microcavity optical waveguide. Under the combined action of the optical force and the capillary hydrodynamic force, two columns and four columns of stable trapping points at different positions can be generated respectively, and two columns and four columns of independent cell strings in the three-dimensional space can be trapped and manipulated respectively. The embodiments of the present disclosure can achieve multi-column stable trapping and spatial arrangement of particles in the three-dimensional space.

[0139] In summary, in the cell manipulation device provided by the embodiments of the present disclosure, the laser light source forms a focal point at the port of the microcavity cascaded optical tweezers through multiple reflections and refractions inside and on the side walls of the microcavity optical waveguide, thereby capturing and manipulating the cells at the port of the microcavity cascaded optical tweezers. The microcavity cascaded optical tweezers formed by coupling the optical fiber probe and the microcavity optical waveguide can simplify the device structure and achieve high-throughput capture of cells. In addition, by adjusting the coupling parameters between the microcavity optical waveguide and the micro-nano optical fiber probe, the operating parameters of the laser, monitoring the back-reflection signal of the cells, and modulating the output light of the light source module, etc., the integration and integration of multifunctional cell manipulation are realized.

[0140] In addition, the present disclosure also provides a cell manipulation method, which can be applied to the cell manipulation device in the above embodiments. The above descriptions can all be used to implement any cell manipulation method provided by the present disclosure. For the corresponding technical solutions and descriptions, reference can be made to the corresponding records in the device part, and details will not be repeated here.

[0141] The cell manipulation method provided by the embodiments of the present disclosure includes: setting a laser light source based on the cell manipulation method; transmitting the laser light source through the optical fiber probe, and forming an optical force for manipulating cells in the microcavity optical waveguide based on the laser light source.

[0142] Wherein, the optical fiber probe and the microcavity optical waveguide are nested and inserted to form a microcavity cascaded optical tweezers; one end of the optical fiber probe is connected to the light source module for transmitting the laser light source, and the other end is nested and inserted with the microcavity optical waveguide;

[0143] The microcavity optical waveguide is provided with an opening and a hollow cavity for cell circulation, and the microcavity cascaded optical tweezers are configured to capture the cells in the sample solution into the hollow cavity of the microcavity optical waveguide through the opening at least based on the capillary force formed at the nested insertion position and the optical force formed by the laser light source, and are configured to be able to perform at least one cell manipulation.

[0144] In some embodiments, the functions or modules included in the device provided by the embodiments of the present disclosure can be used to execute the methods described in the above method embodiments. The specific implementation can refer to the description of the above method embodiments. For the sake of brevity, details will not be repeated here.

[0145] The above have described the embodiments of the present disclosure. The above descriptions are exemplary, not exhaustive, and are not limited to the disclosed embodiments. Many modifications and changes are obvious to those of ordinary skill in the art in the technical field without departing from the scope and spirit of the described embodiments. The selection of the terms used herein is intended to best explain the principles of the embodiments, practical applications, or improvements to the technology in the market, or to enable other ordinary technical personnel in the technical field to understand the disclosed embodiments.< / s>

Claims

1. A novel cascade optical tweezers capture device, characterized in that: include: A light source module, used for providing a laser light source; Microcavity cascade optical tweezers, comprising a nested and plugged optical fiber probe and a microcavity optical waveguide; wherein one end of the optical fiber probe is connected to the light source module for transmitting the laser light source, and the other end is nested and plugged with the microcavity optical waveguide; The microcavity optical waveguide is provided with an opening and a hollow cavity for cell circulation, and the microcavity cascade optical tweezers are constructed to capture the cells in the sample solution into the hollow cavity of the microcavity optical waveguide through the opening based on at least the capillary force formed at the nested joint and the optical force formed by the laser light source, and are constructed to be able to perform at least one type of cell manipulation.

2. According to the novel cascade optical tweezers capture device of claim 1, the manipulation performed on cells includes at least one of cell capture, cell transport, cell sorting, and cell array arrangement.

3. The novel cascade optical tweezers capture device according to claim 1 or 2, characterized in that: The light source module is also used to set the parameters of the laser light source of the light source module; Furthermore, the light source module is further configured to set the parameters of the laser light source to meet a first condition when the manipulation is high-throughput cell capture; The first condition includes that the laser light source forms at least one focus in the microcavity optical waveguide, and the resultant force direction of the capillary force and the optical force at the focus adjacent to the opening in the axial direction points into the microcavity optical waveguide.

4. The novel cascade optical tweezers capture device according to claim 3, characterized in that: The light source module is further configured to increase or decrease the power of the laser light source under the first condition when the manipulation is cell delivery.

5. The novel cascade optical tweezers capture device according to claim 3 or 4, characterized in that: The light source module is further configured to adjust the parameters of the laser light source to meet a second condition when the manipulation is cell sorting, and under the second condition, the target cells are sorted into the microcavity optical waveguide; Under the second condition, based on the refractive index and radius value of the target cell, the resultant force of the capillary force and the optical force acting on the target cell in the axial direction points into the microcavity optical waveguide.

6. The novel cascade optical tweezers capture device according to claim 3 or 4, characterized in that: The device also includes a polarization controller, which is connected between the light source module and the microcavity cascade optical tweezers and is used to perform polarization processing on the laser light source to generate a polarized light source; When the polarized light source satisfies the third condition, the cell rotates in the microcavity optical waveguide around the transverse axis of the microcavity optical waveguide.

7. The novel cascade optical tweezers capture device according to claim 3 or 4, characterized in that: The light source module is further configured to adjust the parameters of the laser light source to meet a fourth condition when the manipulation is a cell array arrangement; Under the fourth condition, the captured cells are arranged in an array in the microcavity optical waveguide; The fourth condition includes: the light source transmitted to the optical fiber probe includes multiple columns of sub-light beams, and at least two columns of sub-light beams meet the first condition, correspondingly forming at least two columns of cell arrangement.

8. The novel cascade optical tweezers capture device according to claim 1, characterized in that: The device also includes: a display module arranged above the microcavity cascade optical tweezers, which is used to obtain images of the microcavity cascade optical tweezers capturing and manipulating cells in real time.

9. The novel cascade optical tweezers capture device according to claim 1, characterized in that: The opening is in a closed shape relative to two sides of the hollow cavity.

10. A novel cascade optical tweezers capture method, characterized in that: The method is applied in the novel cascade optical tweezers capture device as claimed in any one of claims 1 to 9, and the method comprises: Setting a laser light source based on the cell manipulation method; The laser light source is transmitted through the optical fiber probe, and an optical force for manipulating cells is formed in a microcavity optical waveguide based on the laser light source, wherein the optical fiber probe and the microcavity optical waveguide are nested and plugged to form a microcavity cascade optical tweezers; wherein one end of the optical fiber probe is connected to the light source module for transmitting the laser light source, and the other end is nested and plugged with the microcavity optical waveguide; The microcavity optical waveguide is provided with an opening and a hollow cavity for cell circulation, and the microcavity cascade optical tweezers are constructed to capture the cells in the sample solution into the hollow cavity of the microcavity optical waveguide through the opening based on at least the capillary force formed at the nested joint and the optical force formed by the laser light source, and are constructed to be able to perform at least one type of cell manipulation.

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