CN110993140A

CN110993140A - Single-core fiber-multi-core fiber combined optical motor system

Info

Publication number: CN110993140A
Application number: CN201911120280.9A
Authority: CN
Inventors: 苑立波; 申泽
Original assignee: Guilin University of Electronic Technology
Current assignee: Guilin University of Electronic Technology
Priority date: 2019-11-15
Filing date: 2019-11-15
Publication date: 2020-04-10

Abstract

The invention provides an optical motor system with functions of capturing and rotating cells. The optical motor system includes: a laser 1 for generating the required light source; a fiber beam splitter 2 for dividing the laser light path into N+1 paths; an attenuator array 3 for connecting the N+1 light paths respectively and controlling the power of each light path; wherein A multi-core fiber combiner 4 that couples N beams to a multi-core fiber arm 5-1 for manipulating cells; uses the remaining beam as a single-mode fiber arm 5-2 for cell manipulation; A microfluidic chip 6 holding a pair of multi-core fiber arms, delivering cell flow, and providing an experimental environment; a microscopic imaging system 7 for observing the experimental operation process. The invention can be used for capturing and rotating operation of single cell or multiple cells, capturing and arranging tiny particles, and can also provide power for micro-robots or micro-scale instruments. It can be widely used in the fields of cell analysis, drug development and micro-manufacturing.

Description

Single-core optical fiber-multi-core optical fiber combined optical motor system

(I) technical field

The invention relates to a single-core optical fiber-multi-core optical fiber combined optical motor system, which can be used for capturing single cells or multiple cells and rotating operation thereof, capturing and arranging micro particles, and also can provide power for micro robots or micron-scale instruments. Can be widely used in the fields of cell analysis, drug development and micro-manufacturing.

(II) background of the invention

A single-core optical fiber-multi-core optical fiber combined optical motor system is a development and application of optical tweezers.

In the field of optical tweezers, the Ashkin laboratory group in bell laboratories has made pioneering work. In 1970, Ashkin speculated that a focused laser could push particles on the micron scale by estimation. He placed latex microspheres with a diameter of 0.6-2.5 um in water and focused a two virtual argon ion laser at a power of 1w in the water, and found that these particles can be accelerated along the optical axis. This experiment was the first to clearly observe the effects of light pressure and confirm his speculation.

Ashkin finds that not only can particles be pushed away in the direction of the optical axis, but also that the beam has a lateral attraction to particles with a higher refractive index than the surrounding medium. In contrast, there is a lateral thrust for particles having a lower refractive index than the surrounding medium. By utilizing the property, the Ashkin focuses the two lasers at the same position by relatively incidence, and the result shows that a potential well which can transversely suck and fix the particle is generated at the position where the axial forces of the two lasers are mutually counteracted. This is the prototype of "dual beam capture".

In 1985, where single beam laser atoms were studied, Ashkin attempted to grab larger particles with a similar device and found that: these particles can be stably captured by only highly focusing a single laser beam. Thus, in 1986, Ashkin et al indicated that a single laser beam was highly focused and that particles could be stably trapped at the laser beam focal point. The optical trapping of such a single laser beam becomes "optical tweezers" which can grab particles with diameters ranging from tens of nanometers to tens of micrometers without mechanical contact.

The property of optical tweezers that can manipulate microparticles without mechanical contact has attracted considerable interest in the life sciences community. In 1987, Ashkin et al first used optical tweezers to capture bacterial viruses in life sciences. The optical tweezers technology is widely applied to life science research, and provides a powerful tool for cell research and biological pharmacy.

Cell biology is a subject for studying the structure, function and various life laws of cells at the microscopic, sub-microscopic and molecular levels by applying modern physical, chemical and molecular biological methods. It developed from cytology. Since cells have already been investigated not only purely for individual cells, organelles and biological macromolecules or for individual life phenomena, but also for organic integration of these, their interrelations and their relationship to the environment are explored from dynamic processes.

Cell biology and molecular biology, neurobiology and ecology are the four fundamental subjects of life science. From the life structure level, cell biology is intermediate between molecular biology and split biology, and plays an important role in starting from the top down by linking and permeating with the molecular biology and the split biology. The shadow of cell biology can be seen in the disciplines of genetics, development, reproduction, nerve, immunity, and the like, and in the development of medical and biological high technology. For example, the metabolism and regulation of biological macromolecules such as proteins, nucleic acids, glycoproteins in biochemistry, gene expression and regulation, cell signal transduction, abnormal cell proliferation, physiological substance transport, cell signal transduction, etc., and pathological cell aging and death, inflammation, canceration, etc. … … are all closely related to the chemical composition, structure and function of related substances in cell biology and the vital activities of related organelles. Therefore, cell biology is considered as an important foundation of modern life science, is one of the leading subjects in life science at present, and the research on cell biology tends to promote the vigorous development of life science.

An optical cell stretcher (Biophys, The optical stretcher: a novel laser to micromanipulation cells,81: 767-. However, additional force is received at the surface of the trapped particles, which allows the particles to be stretched in the direction of the optical axis. The elastic properties of the media particles, including the properties of some biological material such as cells, can thus be measured. Since the beam is not focused, the radiation damage is small and the surface force is not limited by the optical power. And the experiments measured human erythrocytes and mouse fibroblasts. However, many actual particles to be measured are not isotropic, and this method can only measure the surface elastic characteristics of the measured object in a certain direction, and cannot turn over the particles and thus cannot measure the elastic characteristics in any direction, so that the detected elastic characteristics have contingency.

A single-degree-of-freedom cell posture angle regulation method is introduced in a patent with the application number of 201811200059. X. The method comprises the following steps: step 1, collecting cell images through a CCD camera, and identifying target cells through an image processing algorithm; step 2, using dual optical tweezers to act on the target cell to rotate the target cell; step 3, obtaining the position of the dual optical tweezers relative to the target cells when the next frame of image is obtained through a cell rotation control algorithm; step 4, redistributing the positions of the dual optical tweezers to enable the target cells to rotate to a new attitude angle; step 5, acquiring the attitude angle of the target cell in real time through an image processing algorithm, and judging whether the target cell rotates to a desired position; if yes, ending; if not, returning to the step 3. The method for regulating and controlling the attitude angle of the cell with the single degree of freedom can automatically realize the rotation control of the cell with the single degree of freedom. Although the cell posture can be adjusted at any angle by rotating the cell, the optical tweezers position needs to be redistributed in each adjustment, the operation is complex, the requirement on the device precision for adjusting the optical tweezers position is high, and the adjustment to the expected position is difficult.

In addition, an optical cell rotator (Kreying M K, Kiessling T, Fritsch A, et al. optical cell rotator [ J ]. Optics Express,2008,16(21): 16984-. The method adopts two optical fibers arranged oppositely to transmit laser, so that the captured particles are placed between the two light beams. The two optical fiber transmissions respectively transmit two asymmetric laser beams. One of the arms is inserted into a ceramic ferrule, the other single mode fiber is soldered to a multimode fiber with an offset, and the multimode fiber is inserted into the other ceramic ferrule. Two fiber arms are oppositely arranged through two ceramic ferrules. The two fiber arms may transmit two asymmetric laser beams and the trapped particles may be rotated about the optical axis by rotating the ceramic ferrule of the multimode fiber. The experimental group carries out relevant experiments on human erythrocytes, promyelocytic leukemia cells and cell cluster, and proves the feasibility of the experimental group. However, this method only allows the trapped particles to rotate around the optical axis, and the two poles of the axis of rotation are not visible through the microscope. In addition, the method of rotating cells by rotating a ceramic ferrule has extremely high requirements on mechanical precision and great difficulty.

The present invention provides a single-core fiber-multi-core fiber combined optical motor system under the above background. The cell can be captured, and the cell can be controlled to rotate in multiple directions by adjusting the output light beams of each fiber core, so that the cell posture can be adjusted. Compared with the prior art, the invention adopts the novel multi-core optical fiber, highly integrates multiple paths of light beams, and has small volume and low manufacturing cost. The universal rotation of the cell can be realized only by controlling the output light field of the corresponding fiber core, and the end face of the optical fiber adopts a flat end face without tapering, so that the operation is simpler and the equipment manufacture is easier. The invention provides a powerful tool for cell tomography and has profound significance for cell analysis, biological research and micro-manufacturing.

Disclosure of the invention

The invention aims to provide a single-core optical fiber-multi-core optical fiber combined optical motor system which can be used for cell capture, rotation and micro-manufacturing.

The purpose of the invention is realized as follows:

the optical motor system includes: a laser 1 for generating a desired light source; an optical fiber beam splitter 2 for dividing the laser light path into N +1 paths; an attenuator array 3 which is respectively connected with the N +1 light paths and controls the power of each light path; wherein the N light beams are coupled to a multi-core fiber combiner 4 of a multi-core fiber arm 5-1 for manipulating the cells; the rest light beam is a single-mode fiber arm 5-2 used for controlling cells; a microfluidic chip 6 for holding a pair of multi-core fiber arms, transporting cell flow, and providing an experimental environment; a microscopic imaging system 7 for observing the course of the experimental procedure. In the system, laser is led out from a laser 1 to a fiber beam splitter 2 through a standard single-mode fiber, so that one laser beam is split into N +1 laser beams. The attenuator array 3 includes N +1 attenuators. The N +1 beams emitted by the fiber splitter are respectively connected to N +1 attenuators in the attenuator array 3. N optical paths led out from the attenuators are connected to a multi-core optical fiber beam combiner 4, the multi-core optical fiber beam combiner 4 is connected with a multi-core optical fiber arm 5-1, and the other 1 optical path led out from the attenuators is connected to a single-mode optical fiber arm 5-2. The single-mode fiber arm 5-1 and the multi-core fiber arm 5-2 are used for capturing and rotating cells. The microfluidic chip 6 is fixed with two optical fiber arms, the microfluidic chip 6 is also provided with two microfluidic channels for inputting and outputting cell flows, and cells to be researched flow through the two microfluidic channels on the microfluidic chip 6 and are controlled by the two optical fiber arms 5-1 and 5-2. The microscopic imaging system 7 comprises a CCD and a computer, and can present the experimental process on the microfluidic chip in real time. The rotating cellular phase acts as a "rotor" and the laser provides the motive force, forming an optical motor system.

The multi-core fiber used in the system has at least two cores, and one core is arranged in the middle of the fiber. As shown in fig. 2, the pictures illustrate only the dual, three, five and seven core fibers, but are not limited to these four.

When the optical fiber is placed, the central core of the multi-core optical fiber is aligned with the fiber core of the single-mode optical fiber. Here illustrated with a three-core fiber, as in fig. 3.

The cell flow passes through a microfluidic channel in the microfluidic chip 6, and the cell flow passes between a pair of optical fiber ends, as shown in fig. 4, to provide the cell to be observed for the experiment. The laser 1 emits a 980nm light source, the light source passes through the optical fiber beam splitter 2 and the attenuator array 3, and the attenuator in the attenuator array is adjusted, so that the central core of the multi-core optical fiber 5-1 and the single-mode optical fiber generate light fields with the same power. The forces exerted by the cells are mutually counteracted in the longitudinal direction and are thus stably captured between the two fiber ends. The purpose of capturing cells is achieved. The condition of the cell flow and the capture condition are observed in real time on a computer display screen through a microscopic imaging system 7. The scattering force of the light field transmitted by each fiber arm on the cell is as follows:

the force acting on a cell of volume V can be seen as a tension on the surface S of the cell,

is the tension tensor acting on a unit area. MakingThe force applied to the surface element is

Wherein

In the formula,

T_ijthe meaning of (1) is the component of the force acting on a unit area perpendicular to the j axis on the i axis. n is_jIs the outward normal vector of the cell' S outer surface S perpendicular to the j-axis.

In the rectangular coordinate system, the direction of the z-axis is the beam propagation direction of the multi-core fiber 5-1.

Adjusting the attenuator 3 to make the central core reach the transmitted optical field with proper intensity, and when the longitudinal component F of the multi-core fiber arm 5-1_z1Longitudinal component F of single mode fiber arm 5-2_z2Has a relationship of F_z1＝-F_z2When the resultant force of the cells in the longitudinal direction is zero, the cells are stably captured between the two fiber end faces.

If the cell rotation is controlled, the attenuator 3 is adjusted, and the optical field emitted by the corresponding rotation control core is controlled according to the requirements of different rotation angles. The relationship of the torque M acting on the cells is

Wherein,

is a unit vector in the y direction in a rectangular coordinate system,

is a position vector with respect to the axis of rotation,

is an outward method of the outer surface S of the cellAnd (5) vector quantity.

As time average of surface tension

For example, using single-core and double-core fibers to rotate the cells about the y-axis. As shown in FIG. 5, by adjusting the attenuator of the attenuator array 3 that controls the rotation control core, and thus adjusting the optical field of the rotation control core of the two-core fiber arm 5-1, the differential torque M of the cell rotation can be controlled, and thus the direction and speed of the cell rotation can be adjusted.

(IV) description of the drawings

Fig. 1 is a schematic diagram of an apparatus of a single-core optical fiber-seven-core optical fiber combined optical motor system.

Fig. 2 is a schematic view of a multi-core optical fiber.

FIG. 3 is a schematic view of a single-core fiber-three-core fiber arrangement.

FIG. 4 is a schematic view of a microfluidic chip. Comprises a microfluidic channel input end 14-1, a microfluidic channel output end 14-2, trapped cells 15 and multi-core fiber arms 5-1 and 5-2.

FIG. 5 is a schematic diagram of the rotation of cells around the y-axis using a single-core fiber, a two-core fiber.

FIG. 6 is a schematic of the core used when a single mode fiber-seven core fiber combined optical motor system grabs particles and rotates cells about the y-axis of the Cartesian coordinate. Comprises a seven-core fiber arm 5-1 and a single-mode fiber arm 5-2.

FIG. 7 is a schematic view of the particle force analysis when the single mode fiber-seven core fiber combined optical motor system grabs the particle and rotates the cell around the y-axis of the rectangular coordinates. The reference plane is xoz plane and comprises seven-core fiber arm 5-1, single-mode fiber arm 5-2, central core 9, scattering force 10, trapped cell 11 and rotating shaft 12.

(V) detailed description of the preferred embodiments

The invention will be described in detail below by taking a single mode fiber-seven core fiber combined optical motor system as an example.

Example 1: based on the rotation control of the single-mode fiber-seven-core fiber combined optical motor system on human erythrocytes:

fig. 1 is an optical motor system based on a single mode fiber-seven core fiber combination, in which laser is led out from a laser 1 to a fiber beam splitter 2 through a standard single mode fiber, so as to split one laser into 8 laser beams. The attenuator array 3 contains 8 attenuators. The 8 beams from the fiber splitter are connected to 8 attenuators in the attenuator array 3. 7 light paths led out from the attenuators are connected to a seven-core optical fiber beam combiner 4-1, and the other 1 light path led out from the attenuators is connected to a single-mode optical fiber arm 5-2. The single-mode fiber arm 5-1 and the multi-core fiber arm 5-2 are used for capturing and rotating cells. The microfluidic chip 6 is fixed with two optical fiber arms, the microfluidic chip 6 is also provided with two microfluidic channels for inputting and outputting cell flows, and cells to be researched flow through the two microfluidic channels on the microfluidic chip 6 and are controlled by the two optical fiber arms 5-1 and 5-2. The microscopic imaging system 7 comprises a CCD and a computer, and can present the experimental process on the microfluidic chip in real time. The rotating cellular phase acts as a "rotor" and the laser provides the motive force, forming an optical motor system.

Red blood cells are about 7um in diameter and have several advantages as experimental subjects because they have no internal organelles, approaching the isotropic, soft-textured dielectric sphere model. Simple structure, less interference factors and convenient research. When the system works, the capture light source 1 emits laser with the power of 30mw and the wavelength of 980nm, and the whole experimental operation process is observed through the ocular lens 9, the CCD6 and the computer 10. The attenuator 3 is adjusted, so that the laser emitted by the central core of the seven-core fiber arm 5-1 and the laser emitted by the single-mode fiber arm 5-2 can be stably captured to the red blood cells, and the other control rotating cores do not emit laser. If the power of the light field emitted by the two central cores is the same, the red blood cells are trapped in the middle of the light field. If the power of the central core of the seven-core optical fiber or the single-mode optical fiber is changed, the cells are displaced towards the fiber core with low power. The power is changed by adjusting the attenuator of the attenuator array 3 corresponding to the core.

If the cell is required to rotate around a certain rotation axis, the corresponding rotation control core is adjusted by adjusting the attenuator 3, so that the laser emitted from the end of the optical fiber acts on the cell to generate a rotation torque. For example, when a cell is required to rotate about the y-axis of the rectangular coordinate, as shown in FIG. 6, the attenuator 3 is adjusted so that the rotation of the seven-core fiber arm 5-1 controls the core 4 so that the scattering force in its optical field can generate the torque required to rotate the cell about the y-axis, and the force analysis of the red blood cell is shown in FIG. 7. At this time, the red blood cells can be observed to rotate clockwise around the y-axis by the computer monitor.

Claims

1. A single-core fiber-multi-core fiber combined optical motor system. The optical motor system includes: a laser 1 for generating the required light source; a fiber beam splitter 2 for dividing the laser light path into N+1 paths; an attenuator array 3 for connecting the N+1 light paths respectively and controlling the power of each light path; wherein Coupling N beams to a multi-core fiber combiner 4 of a multi-core fiber arm 5-1 for manipulating cells; converting the remaining one beam into a single-mode fiber arm 5-2 for manipulating cells; for clamping A microfluidic chip 6 holding a pair of multi-core fiber arms, delivering cell flow, and providing an experimental environment; a microscopic imaging system 7 for observing the experimental operation process. In the system, the laser is led out from the laser 1 to the fiber beam splitter 2 by a standard single-mode fiber, so that one laser is divided into N+1 lasers. The attenuator array 3 contains N+1 attenuators. The N+1 beams emitted by the fiber beam splitter are respectively connected to N+1 attenuators in the attenuator array 3 . The N optical paths from the attenuator are connected to the multi-core fiber combiner 4, the multi-core fiber combiner 4 is connected to the multi-core fiber arm 5-1, and the other one optical path from the attenuator is connected to the single-mode fiber arm 5 -2. Single-mode fiber arm 5-1 and multi-core fiber arm 5-2 are used to capture and spin cells. The microfluidic chip 6 fixes two optical fiber arms, and the microfluidic chip 6 also has two microfluidic channels for input and output cell flow. The flow channel is controlled by two fiber optic arms 5-1 and 5-2. The microscopic imaging system 7 includes a CCD and a computer, which can present the experimental process on the microfluidic chip in real time. The rotating cellular phase acts as a "rotor," powered by a laser, creating an optical motor system.

2 . The combined optical motor based on single-core fiber to multi-core fiber according to claim 1 . The multi-core optical fiber used in the system is characterized in that the optical fiber has more than two cores and a core in the center of the cladding. The higher the number of cores, the more directions the cell can spin.

3. The combined optical motor based on single-core fiber to multi-core fiber according to claim 1. The system is used in combination with a fiber splitter 2, an attenuator array 3 and a multi-core fiber combiner 4, so as to flexibly control the output light field of each core of the multi-core fiber.