CN106646843B - Device for accurately controlling movement of single cells and ejection screening - Google Patents

Device for accurately controlling movement of single cells and ejection screening Download PDF

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CN106646843B
CN106646843B CN201611262479.1A CN201611262479A CN106646843B CN 106646843 B CN106646843 B CN 106646843B CN 201611262479 A CN201611262479 A CN 201611262479A CN 106646843 B CN106646843 B CN 106646843B
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optical fiber
fiber
light
core
cores
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CN106646843A (en
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张永慧
魏勇
刘春兰
刘璐
朱宗达
刘丹
潘连红
庞毅
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Chongqing Three Gorges Medical College
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    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00Microscopes
    • G02B21/32Micromanipulators structurally combined with microscopes
    • GPHYSICS
    • G21NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21KTECHNIQUES FOR HANDLING PARTICLES OR IONISING RADIATION NOT OTHERWISE PROVIDED FOR; IRRADIATION DEVICES; GAMMA RAY OR X-RAY MICROSCOPES
    • G21K1/00Arrangements for handling particles or ionising radiation, e.g. focusing or moderating
    • G21K1/006Manipulation of neutral particles by using radiation pressure, e.g. optical levitation

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Abstract

The invention discloses a device for accurately controlling movement and ejection screening of single cells, wherein six fiber cores in a seven-core optical fiber are circularly arranged, a seventh fiber core is positioned at the center of the circle, one end face of the seven-core optical fiber is ground into three groups of symmetrical inclined planes to form a seven-core optical fiber probe, and the single cells can be captured by light trapping force formed by convergence of refracted light of each group of fiber cores; the light injection optical fiber group is formed by circularly and tightly arranging seven light injection single-mode optical fibers, and the coupling lens group compresses the distance between light beams to enable the distance to be matched with the size of the space between fiber cores in the seven-core optical fiber probe; the optical fiber beam splitter equally divides the energy of the output light of the laser light source into seven beams, and the seven beams are respectively connected with the seven light injection single-mode optical fibers through the optical fiber attenuators. The three groups of converged light beams with different angles can capture one to three cells, can realize the precise movement of single cells among three capture points, can also capture the light interruption of a single-side fiber core after the single cells are captured, can realize the ejection screening of the single cells in seven directions, and can be widely applied to the field of medical single cell control.

Description

Device for accurately controlling movement of single cells and ejection screening
Technical Field
The invention belongs to the field of single cell accurate operation, and particularly relates to a device for accurately controlling single cell movement and ejection screening.
Background
The light has energy and momentum at the same time, the momentum of the light can interact with the substance to generate a potential well effect, and the potential well effect of the light can be used for capturing micro particles. The optical tweezers for capturing single cell is a tool for capturing and manipulating tiny particles by using the gradient force and scattering force of the light intensity distribution. In 1986, ashkin et al first proposed a method for controlling the spatial movement of a single-beam laser operated microparticle in an "Observation of a single-beam gradient for optical trap for a dielectric particle" that could attract the microparticle to be fixed at the waist of the light. This is the concept of "optical tweezers" that was first proposed. The optical tweezers have the characteristics of accurate positioning, no pollution to liquid environment, no direct contact with a captured object, no damage to the captured object and the like in the working process, so that the optical tweezers are rapidly developed in various disciplines, particularly in the fields of physics, biomedicine, colloid science and the like.
The single fiber optical tweezers made of the optical fiber with a special structure has a series of advantages of small size, high integration level, convenient operation, large capture force, stability and the like, and has attracted much attention in recent years. The invention patent with the patent number zl200810064013.X provides multi-optical tweezers integrated on a single optical fiber, and provides an optical fiber with a plurality of fiber cores, wherein the end face is ground and processed to form a symmetrical or asymmetrical polygonal wedge shape, so that a plurality of particles can be captured simultaneously, and the number of capture points can be adjusted by adjusting the number of the fiber cores. However, the present invention has the following problems: each capture point cannot be controlled independently, so that captured non-target particles cannot be removed independently; the movement of the particles cannot be realized on the premise of keeping the optical tweezers still.
Disclosure of Invention
In view of this, the present invention provides a device for precisely controlling movement and ejection screening of single cells, which has a small volume, a simple structure, a low cost, and a plurality of capture points, and can stably capture strip-shaped particles and sheet-shaped single cells, and also can precisely move and eject screen single cells in seven directions.
In order to achieve the purpose, the invention provides the following technical scheme: a device for accurately controlling single cell movement and ejection screening comprises a seven-core optical fiber probe 1, a light injection optical fiber group 2, a coupling lens group 3, a laser light source 4, an optical fiber beam splitter 5 and an optical fiber attenuator 6; six fiber cores in the seven-core optical fiber are circularly arranged, a seventh fiber core is positioned in the center of the circle, the end face of one end of the seven-core optical fiber is ground into three groups of symmetrical inclined planes to form the seven-core optical fiber probe 1, and single cells can be captured by light trapping force formed by converging refracted light of each group of fiber cores; the optical fiber beam splitter 5 is correspondingly connected with seven light injection single-mode optical fibers in the light injection optical fiber group 2 through the optical fiber attenuator 6, the light injection optical fiber group 2 guides the light into the seven-core optical fiber probe 1 through the coupling lens group 3, so that the distance between seven light beams of the light injection optical fiber group 2 is compressed, and the distance is matched with the size of the fiber core space in the seven-core optical fiber probe 1.
Furthermore, fiber cores 1-1, 1-2, 1-3, 1-4, 1-5 and 1-6 in the seven-core optical fiber probe 1 are circularly arranged, the fiber cores 1-7 are positioned at the center of a circle, the space between all the fiber cores is 35 μm, the diameter of each fiber core is 8 μm, and the diameter of a fiber cladding is 125 μm.
Further, in the seven-core optical fiber probe 1, the fiber cores 1-1 and 1-4, the fiber cores 1-2 and 1-5, and the fiber cores 1-3 and 1-6 are respectively ground into three groups of symmetrical wedges by taking the fiber cores 1-7 as a symmetry axis, the three groups of grinding angles are different, and the grinding angles of the groups are all between 10 and 17 degrees.
Further, the light injection optical fiber group 2 is formed by tightly arranging seven single-mode optical fibers, six optical fibers are arranged on the periphery in a circular shape, and a seventh optical fiber is located in the center of the circular shape and tightly fixed with each other.
Further, the laser source 4 is a laser source with a wavelength of 980nm or 1064nm, the total power of the laser source is more than 300mW, and the seven paths of power can be adjusted by an optical fiber attenuator.
Further, the optical fiber beam splitter 5 splits the output light of the laser light source into seven laser beams with equal light intensity.
The invention has the beneficial effects that: 1. the device has three capture points at different positions, and thus can be used for stably capturing elongated particles such as escherichia coli. 2. The light intensity at each trapping point can be controlled individually to control the optical trapping force at each trapping point, thus enabling the movement and rotation of the particles. 3. And after capturing, the fiber core on the single side is cut off, and seven-direction ejection screening of single cells is realized. 4. The adopted device has low price and simple manufacture, is suitable for large-scale production, and has better application prospect in the fields of biomedicine and the like which need single-cell precise operation.
Drawings
In order to make the object, technical scheme and beneficial effect of the invention more clear, the invention provides the following drawings for explanation:
FIG. 1 is a schematic diagram of a system for precisely controlling the movement and ejection of single cells;
FIG. 2 is a schematic diagram of a seven-core fiber optic probe;
FIG. 3 is a schematic diagram of a set of symmetric cores refracting and then capturing single cells;
FIG. 4 is a schematic diagram of three groups of angle focus positions of the seven-core fiber probe.
Detailed Description
Preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings.
As shown in the figure, the device for accurately controlling the movement and ejection screening of single cells comprises a seven-core optical fiber probe 1, a light injection optical fiber group 2, a coupling lens group 3, a laser light source 4, an optical fiber beam splitter 5 and an optical fiber attenuator 6; six fiber cores in the seven-core optical fiber are circularly arranged, a seventh fiber core is positioned in the center of the circle, the end face of one end of the seven-core optical fiber is ground into three groups of symmetrical inclined planes to form the seven-core optical fiber probe 1, and single cells can be captured by light trapping force formed by converging refracted light of each group of fiber cores; the optical fiber beam splitter 5 is correspondingly connected with the seven light injection single-mode optical fibers in the light injection optical fiber group 2 through the optical fiber attenuator 6, the light is guided into the seven-core optical fiber probe 1 through the coupling lens group 3 by the light injection optical fiber group 2, so that the distance between the seven light beams of the light injection optical fiber group 2 is compressed, and the distance is matched with the size of the fiber core interval in the seven-core optical fiber probe 1. The light intensity of the focused light beam can be adjusted by adjusting and changing the optical fiber attenuator 6; three groups of converged light beams with different angles can capture one to three cells, can realize the precise movement of single cells among three capture points, and can also capture the light interruption of a single-side fiber core after the single cells are captured, thereby realizing the ejection screening of the single cells in seven directions.
Specifically, fiber cores 1-1, 1-2, 1-3, 1-4, 1-5 and 1-6 in the seven-core optical fiber probe 1 are circularly arranged, the fiber cores 1-7 are positioned at the center of a circle, the space between all the fiber cores is 35 μm, the diameter of each fiber core is 8 μm, and the diameter of a fiber cladding is 125 μm; the end face of one end of the seven-core optical fiber is ground into three groups of symmetrical inclined planes by utilizing a bare optical fiber precision grinding technology, namely the fiber cores 1-1 and 1-4, the fiber cores 1-2 and 1-5 and the fiber cores 1-3 and 1-6 are respectively ground into three groups of symmetrical oblique wedges by taking the fiber cores 1-7 as a symmetrical axis to prepare the seven-core optical fiber probe, the three groups of grinding angles are different, and the grinding angles of the groups are all between 10 and 17 degrees.
Specifically, the light injection fiber group 2 is formed by tightly arranging seven single-mode fibers, six fibers are arranged on the periphery in a circular shape, and the seventh fiber is located in the center of the circular shape and tightly fixed with each other. The laser light source 4 is a laser light source with the wavelength of 980nm or 1064nm, the total power of the laser light source is more than 300mW, and the seven paths of power can be adjusted by an optical fiber attenuator. The optical fiber beam splitter 5 splits the output light of the laser light source into seven laser beams with equal light intensity.
Example 1
1. Taking a section of seven-core optical fiber with the length of 1m, stripping a coating layer of the optical fiber by using an optical fiber wire stripper for 50mm at one end of the optical fiber, dipping a non-woven fabric into a mixed solution of alcohol and ether, and repeatedly wiping an outer cladding layer of the optical fiber until the outer cladding layer is cleaned for later use;
2. cutting the cleaned end face of the optical fiber to be flat by using an optical fiber cutting knife;
3. using a bare optical fiber precision cone grinding machine, wherein fiber cores at every two opposite angles are a pair, and three pairs of fiber cores are respectively ground into symmetrical wedge shapes with angles of 11 degrees, 14 degrees and 17 degrees to prepare a seven-core optical fiber probe (as shown in figure 2);
4. taking seven segments of single-mode optical fibers, wherein the length of each segment is 1m, stripping a coating layer of each optical fiber by 50mm at one end of each optical fiber, dipping a non-woven fabric into a mixed solution of alcohol and ether, and repeatedly wiping an outer cladding layer of each optical fiber until the optical fiber is cleaned for later use;
5. cutting the end faces of the seven sections of cleaned single-mode optical fibers flatly by using an optical fiber cutter, so that the length of the optical fiber with the coating layer removed is 20mm;
6. arranging the seven single-mode fibers in the step 5 in a shape that six single-mode fibers are arranged in a circle and a seventh single-mode fiber is arranged in the middle of the seven single-mode fibers, aligning the end faces, fixing the seven single-mode fibers by using epoxy glue, ensuring that the arrangement shape is a standard peripheral six-fiber arrangement circle, and arranging the seventh single-mode fiber in the middle of the seven single-mode fibers to form a light injection fiber group (as shown in figure 1);
7. taking seven paths of optical fiber beam splitters, and splitting output light of a laser light source with the wavelength of 980nm into seven beams with equal intensity;
8. connecting 7 identical optical fiber attenuators to the seven output optical fibers of the optical fiber beam splitter in the step 7;
9. connecting the seven optical fibers in the step 8 with the seven single-mode optical fibers in the step 6 in sequence, and connecting the seven optical fibers with the seven single-mode optical fibers in the step 6 according to the fiber cores 1-1 and 1-4; a fiber core 1-2 and a fiber core 1-5; cores 1-3 are grouped with the order of cores 1-6 to facilitate differentiated control.
10. Clamping the light injection optical fiber group in the step 6 on the side of a large-diameter lens of a coupling lens group, flattening the other non-ground end of the seven-core optical fiber probe in the step 3, clamping the other non-ground end on the side of a small-diameter lens of the coupling lens group, and adjusting the relative position to enable the output light beams of the light injection optical fiber group to be completely injected into seven fiber cores of the seven-core optical fiber (as shown in figure 1);
11. the light intensity of each group of beams is adjusted by adjusting the 7 fiber attenuators in step 8, so as to realize the precise movement of the particles among three capture points (such as fig. 3 and 4).
Example 2
As shown in FIG. 1, a device for precisely controlling the movement and ejection screening of single cells. The structure of the optical fiber probe comprises a seven-core optical fiber probe 1, a light injection optical fiber group 2, a coupling lens group 3, a laser light source 4, an optical fiber beam splitter 5 and an optical fiber attenuator 6.
Because the light emitting ends of seven fiber cores of the constructed seven-core optical fiber probe 1 are respectively ground into 3 pairs of wedges with different angles, each pair of cores are refracted and converged to form light beam focus points (as shown in figure 4) with different positions, the central fiber cores 1-7 can be independently used for rejecting captured particles, the optical fiber attenuator is adjusted, one pair of cores are enabled to be light-transmitting, a stable capture point is obtained, if the particles need to be moved, the other one or two pairs of cores can be light-transmitting, the optical fiber attenuator is adjusted, the particle moving direction is adjusted according to the relative strength of light between the cores, if the redundant particles need to be rejected, the central fiber cores are enabled to be light-transmitting, the central fiber core light intensity is adjusted, the particles can be ejected and pushed out along the central core light-injecting direction, and the screening effect is achieved.
Finally, it is noted that the above-mentioned preferred embodiments illustrate rather than limit the invention, and that, although the invention has been described in detail with reference to the above-mentioned preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the scope of the invention as defined by the appended claims.

Claims (3)

1. The utility model provides a device that accurate control unicell removed and launches screening which characterized in that: the device comprises a seven-core optical fiber probe (1), a light injection optical fiber group (2), a coupling lens group (3), a laser light source (4), an optical fiber beam splitter (5) and an optical fiber attenuator (6); six fiber cores in the seven-core optical fiber are circularly arranged, a seventh fiber core is positioned in the center of the circle, the end face of one end of the seven-core optical fiber is ground into three groups of symmetrical inclined planes to form a seven-core optical fiber probe (1), and single cells can be captured by light trapping force formed by converging refracted light of each group of fiber cores; the optical fiber beam splitter (5) is correspondingly connected with seven light injection single-mode optical fibers in the light injection optical fiber group (2) through an optical fiber attenuator (6), the light injection optical fiber group (2) guides light into the seven-core optical fiber probe (1) through the coupling lens group (3) so as to compress the distance between seven light beams of the light injection optical fiber group (2) and enable the distance to be matched with the size of the space between fiber cores in the seven-core optical fiber probe (1);
fiber cores (1-1), (1-2), (1-3), (1-4), (1-5) and (1-6) in the seven-core optical fiber probe (1) are circularly arranged, the fiber cores (1-7) are positioned at the center of a circle, the space between all the fiber cores is 35 mu m, the diameter of each fiber core is 8 mu m, and the diameter of an optical fiber cladding is 125 mu m;
in the seven-core optical fiber probe (1), fiber cores (1-1 and 1-4), fiber cores (1-2 and 1-5) and fiber cores (1-3 and 1-6) are respectively ground into three groups of symmetrical wedges by taking the fiber cores (1-7) as a symmetry axis, the three groups of grinding angles are different, and the grinding angles of the groups are all between 10 and 17 degrees;
the optical fiber beam splitter (5) splits the output light of the laser light source into seven laser beams with equal light intensity.
2. The device for precisely controlling the movement and ejection screening of single cells according to claim 1, wherein: the light injection optical fiber group (2) is formed by tightly arranging seven single-mode optical fibers, six optical fibers are arranged on the periphery in a circular manner, and a seventh optical fiber is positioned in the center of the circular manner and is tightly fixed with each other.
3. The device for precisely controlling the movement and ejection screening of single cells according to claim 1, wherein: the laser light source (4) is a laser light source with the wavelength of 980nm or 1064nm, the total power of the laser light source is more than 300mW, and the seven paths of power can be adjusted through the optical fiber attenuator (6).
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CN107300538A (en) * 2017-08-28 2017-10-27 重庆三峡医药高等专科学校 A kind of unicellular accurate test experience device based on optical fiber

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