A method and sorting device for accurately screening particles having subtle differences based on orbit tracking

Abstract

The application discloses a method and a sorting device for accurately screening particles with slight differences based on track tracing. The method comprises the following steps: (1) using a force matrix, eigenvalues of the force matrix under a linearly polarized Laguerre-Gaussian beam are calculated to obtain an Ep point; (2) two Laguerre-Gaussian beam emission modules for reverse propagation are started; (3) a polarization component is adjusted to adjust the Laguerre-Gaussian beam to be linearly polarized; (4) micro-nano particles are put into a light field, and the micro-nano particles rotate under the radiation pressure of the vortex field; (5) irradiation of the Laguerre-Gaussian beam is maintained until the motion track of the particles no longer changes, and particles with different sizes are screened out through the semi-major axis; or particles with the same radius and different refractive indexes are screened out through the semi-major axis. The application can realize accurate screening of particles with similar sizes, and can also realize screening of particles with the same size but slight differences in refractive indexes.

Description

Technical Field

[0001] This invention relates to a method and sorting device for accurately screening particles with subtle differences based on orbital tracking. Background Technology

[0002] Optical screening based on optical force and optical moment is an important application of optical micromanipulation, especially in the separation of colloidal particles from cells in colloid and cell molecular biology. Optical screening techniques are mainly divided into two categories: active screening. [1-4] Passive screening [5-12] .

[0003] Active screening requires identifying particle properties through fluorescence, magnetic fields, etc., and then using light gradient force or light scattering force to transport the particles to different channels. [1-4] This allows for the screening of particles. Fluorescently labeled cell screening relies on fluorescent probes or staining agents to identify cells by type. When a laser encounters fluorescently labeled cells in a microfluidic stream, the light is scattered into a detector. By analyzing the fluorescence signal, a specific channel is assigned to each cell, thus achieving screening. [4] .

[0004] Passive selection relies on the inherent physical properties of particles, such as size, shape, and refractive index. Particles of different sizes and refractive indices behave differently within a light field, thus eliminating the need for any active identification. [5-10] Optical chromatography utilizes the forces generated by fluid flow and laser radiation pressure (scattering force), both of which depend on the particle properties. When the pressure from the fluid equals the scattering force of the laser, the particles reach equilibrium. Therefore, different particles have different equilibrium positions, enabling spatial separation of suspension components and allowing for the selection of desired particles. [5] More complex passive screening devices utilize static optical potential traps, which are optical lattices typically bonded to fluids. [6-10] The size of particles suspended in a fluid or the refractive index of the material strongly influences the trajectory of particles through an optical lattice. Since optical lattice sieving relies on the interaction between particles and the fluid, moving the optical lattice in a static fluid can sieve microscopic particles, even submicron particles. [7] By utilizing the strength of the interaction between particles and a three-dimensional optical lattice, screening criteria were established, enabling optical screening by size (protein microcapsule drug delivery agents) and by refractive index (colloidal particles). The sorting efficiency approached 100%. [8] The combination of static fluid and dynamic optical lattice minimizes the impact of particle-to-particle interactions. Furthermore, by combining optical trapping and microfluidic technologies on a microchip, and based on cell morphology, size, absorbance, and refractive index, highly efficient separation of dead and living HeLa cells was successfully achieved.[9] .

[0005] However, the size or refractive index of particles currently used in optical screening generally varies considerably, for example, screening polystyrene spheres with diameters of 1 mm, 2 mm, and 5.2 mm. [6] When the differences in particle size or refractive index are very small, effective screening is difficult to achieve. Therefore, improving the sensitivity of optical screening systems to particle size or refractive index is an important direction in optical screening research and has significant implications for the widespread application of optical screening.

[0006] Existing technologies disclose screening devices that use two coherent laser beams to form a striped coherent light field, resulting in a non-uniform light field distribution, thereby separating particles of different sizes. Figure 1 As shown in the diagram, polystyrene microspheres of different sizes will enter the regions of maximum and minimum intensity in the coherent light field, while microspheres of special sizes will not be affected by the light force.

[0007] Figure 1 In the screening device shown, polystyrene microspheres are subjected to pressure generated by the optical field along the direction of the striped light field. The magnitude of the optical pressure varies depending on the size and refractive index of the microspheres; therefore, microspheres of different sizes have different velocities along the direction of the striped light field. A third laser beam, with a polarization state completely perpendicular to the previous two coherent beams, is then introduced, causing the microspheres to experience a force (transverse force) perpendicular to the direction of the striped light field. Microspheres of different sizes experience different transverse forces, and their directions may be opposite. Based on this, microspheres of different sizes can be screened apart. Figure 2 As shown: Using the above device, polystyrene microspheres with diameters of 1μm and 5.2μm are screened. The 5.2μm polystyrene microsphere is located at the point of minimum light field (the center of the two solid lines), and the 1μm polystyrene microsphere is located at the point of maximum light field (the position of the solid lines).

[0008] However, this existing technology can only distinguish particles with relatively large size differences, such as polystyrene microspheres with diameters of 1 μm and 5.2 μm, or 2 μm and 5.2 μm. It still cannot screen particles with very small size differences (such as polystyrene microspheres with diameters of 1 μm and 2 μm).

[0009] Existing patent CN 216911056 U (application number: 202220407993.4) ​​discloses a method for all-optical particle sorting using linearly polarized Gaussian light. The sorting device includes a Gaussian beam emitting module, a shaping component for shaping the Gaussian beam into an elliptical Gaussian beam, a polarization component for adjusting the polarization direction of the Gaussian beam, and an optical guiding component. In this beam, particles are subjected to lateral light force caused by the polarization of the Gaussian beam and gradient force within the elliptical light spot's optical field. The lateral light force is positively correlated with the light intensity and is related to the polarization angle and particle radius. When the incident angle and polarization direction of the Gaussian beam are fixed, particles with different radii achieve a balance between the lateral light force and gradient force at different positions within the elliptical light spot and are stably captured, thus achieving the sorting of particles with different radii. Although this patent proposes an all-optical particle sorting method, it cannot distinguish particles with very small radii, such as particles with 5μm and 5.2μm, because their equilibrium positions almost overlap.

[0010] References

[0011] [1]TNBuican,MJSmyth,HACrissman,GCSalzman,CCStewart,andJ.Martin,Automated single-cell manipulation and sorting by light trapping,Appl.Opt.26,5311(1987).

[0012] [2] Leonard. A. Herzenberg, D. Parks, B. Sahaf, O. Perez, M. Roederer and Leonore A. Herzenberg, The history and future of the fluorescence activated cellsorter and flow cytometry: A view from Stanford, Clin. Chem. 48, 1819 (2002).

[0013] [3]M.Sivaramakrishnan R.Kothandan,D.K.Govindarajan,Y.Meganathan,K.Kandaswamy,Y.Meganathan,K.Kandaswamy,Active microfluidic system for cellsorting and separation.Curr.Opin.Biomed.Eng.13,60(2020).

[0014] [4]Daniel,W.P.Savarimuthu,Uterine Cervical Cancer,(Springer NatureSwitzerlandAG 2019).

[0015] [5]S.J.Hart,A.V.Terray,J.Arnold,and T.A.Leski,Sample concentrationusing optical chromatography,Opt.Express 15,2724(2007).

[0016] [6]P.Jákl,T. M. and P.Zemánek,Static optical sorting in alaser interference field,Appl.Phys.Lett.92,161110(2008).

[0017] [7]I.Ricárdez-Vargas,P.Rodríguez-Montero,R.Ramos-García,and K.Volke-Sepúlveda,Modulated optical sieve for sorting of polydisperse microparticles,Appl.Phys.Lett.88,121116(2006).

[0018] [8]M.P.MacDonald,G.C.Spalding and K.Dholakia,Microfluidic sorting inan optical lattice,Nature,426,421(2003).

[0019] [9]M.Murata,Y.Okamoto,Y.S.Park,N.Kaji,M.Tokeshi,Y.Baba,Cellseparation by the combination of microfluidics and optical trapping force ona microchip,Anal.Bioanal.Chem.394,277(2009).

[0020]

[10] L.Paterson,E.Papagiakoumou,G.M.V.Garces-Chavez,T.Briscoe,K.Dholakia,Passive optical separation within a‘nondiffracting’light beam,J.Biomed.Opt.12(5),054017(2007).

[0021]

[11] X.G.Liu,J.Q.Li,Q.Zhang and M.G.Dirbeba,Separation of chiralenantiomers by optical force and torque induced by tightly focused vectorpolarized hollowbeams,Phys.Chem.Chem.Phys.21,15339(2019).

[0022]

[12] X.S.Liu,Y.C.Li,X.H.Xu,Y.Zhang and B.J.Li,Optical fan for single-cell screening,J.Biophotonics,13,e201900155(2020).

[0023]

[13] J.Ng,Z.F.Lin,C.T.Chan,and P.Sheng,Photonic clusters formed bydielectric microspheres:Numerical simulations,Phys.Rev.B 72,085130(2005).

[0024]

[14] J.Ng, ZFLin, CTChan, Theory of optical trapping by an opticalvortex beam, Phys.Rev.Lett.104,103601(2010). Summary of the Invention

[0025] The purpose of this invention is to address the shortcomings of existing technologies that cannot effectively screen particles with very small size differences, and to provide a method for precisely screening particles with subtle differences. This screening method can accurately screen particles with similar sizes (refractive indices), for example, screening polystyrene particles with a fixed refractive index and radii of 0.443 μm and 0.445 μm; and particles with radii of 0.4 μm and refractive indices of 3.1 and 3.2.

[0026] This invention provides a method for precisely screening particles with subtle differences based on orbital tracking, comprising the following steps:

[0027] (1) Using the force matrix, the eigenvalues ​​of the force matrix under linearly polarized Laguerre-Gaussian beams are calculated, and its Ep point is obtained;

[0028] (2) Activate the two counter-propagating Laguerre-Gaussian beam emission modules with an orbital angular momentum of 1;

[0029] (3) Adjust the polarization component to make the Laguerre-Gaussian beam linearly polarized;

[0030] (4) Several micro-nano particles are placed in the light field, and under the radiation pressure of the vortex field, the micro-nano particles rotate.

[0031] (5) Continue irradiation with the Laguerre-Gaussian beam until the particle trajectories no longer change, and filter out particles of different sizes through the semi-major axis;

[0032] Alternatively, particles with the same radius but different refractive indices can be filtered out by using the semi-major axis.

[0033] In this invention, the micro / nano particles can be polystyrene microspheres.

[0034] In this invention, the absolute value of the radius difference between the micro and nano particles can be ≤0.2μm, for example ≤0.005μm.

[0035] In this invention, the radii of the micro- and nano-particles can be the same, and the absolute value of the difference in refractive index can be ≤0.5.

[0036] In this invention, the micro / nano particles can be placed in the light field in solid form.

[0037] The present invention also provides a particle size sorting device for micro / nano particles based on orbital tracking, the particle size sorting device comprising:

[0038] (1) Sample stage, provided for placing micro-nano particles to be separated;

[0039] (2) Laguerre-Gaussian beam emission module one, used to emit Laguerre-Gaussian beams;

[0040] Polarization adjustment component one, used to adjust the polarization direction of the Laguerre-Gaussian beam;

[0041] A beam processing component 1 is used to focus a Laguerre-Gaussian beam processed by the shaping component and the polarization adjustment component to the micrometer level;

[0042] The Gaussian beam emitting module, the polarization adjustment component, the spot processing component, and the sample stage are arranged in sequence.

[0043] (3) Laguerre-Gaussian beam emission module two, used to emit Laguerre-Gaussian beams;

[0044] Polarization adjustment component two is used to adjust the polarization direction of the Laguerre-Gaussian beam;

[0045] The second beam processing component is used to focus the Laguerre-Gaussian beam processed by the shaping component and the polarization adjustment component to the micrometer level;

[0046] The sample stage, the second light spot processing component, the second polarization adjustment component, and the second Laguerre-Gaussian beam emission module are arranged in sequence.

[0047] The beam emitted by the first Laguerre-Gaussian beam emitting module and the beam emitted by the second Laguerre-Gaussian beam emitting module are beams that propagate in opposite directions.

[0048] In this invention, the first Laguerre-Gaussian beam emitting module and the second Laguerre-Gaussian beam emitting module can be arranged opposite to each other.

[0049] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0050] (1) When the radius of the particle changes from 0.443μm to 0.445μm, the radius changes by 0.002μm, but the semi-major axis of its corresponding orbital radius changes from 0.1μm to 0.37μm, the semi-major axis changes by nearly 4 times. Therefore, it is possible to accurately screen particles of similar size.

[0051] (2) If the particles have the same radius but different refractive indices, the slight change in refractive index will cause the semi-major axis of the particle's trajectory to change from 0.08μm to 0.32μm, which is nearly 4 times the change. Therefore, it is possible to screen particles with the same size but slight differences in refractive index. Attached Figure Description

[0052] Figure 1 This is a schematic diagram of a screening device in the prior art.

[0053] Figure 2 To utilize Figure 1 The device in the figure filters polystyrene microspheres with diameters of 1 μm and 5.2 μm. The distribution of polystyrene microspheres is shown in the figure. Among them, the 5.2 μm polystyrene microspheres are located at the point of minimum light field (the center of the two solid lines), see Figure (b); the 1 μm polystyrene microspheres are located at the point of maximum light field (the position of the solid line), see Figure (a).

[0054] Figure 3 This is a schematic diagram of the screening device in Example 1.

[0055] Figure 4 The diagram shows the parameter settings and trajectory changes for the polystyrene microsphere screening process in Example 1; wherein:

[0056] Figure (a) shows the change of the imaginary part of the force matrix eigenvalues ​​with the particle radius. The position where the imaginary part changes from 0 to non-zero corresponds to the EP point.

[0057] Figure (b) is the phase diagram corresponding to Figure (a). Only when the particle is within the range enclosed by straight line 1 and curve 2 can it rotate under the influence of the light field.

[0058] Figure (c) shows the dynamic process of a polystyrene microsphere with a radius of 0.443 μm in the xy plane;

[0059] Figure (d) shows the variation of the semi-major axis and semi-minor axis of the elliptical orbit of the polystyrene microsphere with its own radius;

[0060] Figure (e) shows the orbits of polystyrene spheres with different radii;

[0061] Figure (f) shows the distribution of the total force on a polystyrene microsphere with a radius of 0.443 μm at different locations.

[0062] Figure 5 This is a trajectory change diagram of the polystyrene microsphere screening process in Example 1; where:

[0063] Figure (a) shows the imaginary part of the force matrix eigenvalues ​​as a function of the refractive index, with a particle radius of 0.4 μm.

[0064] Figure (b) shows that when the refractive index of the particle changes from 3.07 to 3.25, the radius of the particle's trajectory changes from 0.08 μm to 0.32 μm. The refractive index only changes by about 0.2, but the radius of the particle's orbit increases by 4 times. Detailed Implementation

[0065] The present invention will now be described in detail with reference to the accompanying drawings.

[0066] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0067] Example 1

[0068] An Exceptional Point (EP) is a singularity in a non-Hermitian system. At this point, two or more eigenvalues ​​and eigenvectors become degenerate. By introducing a perturbation, the eigenfrequency splitting near the EP point in an optical non-Hermitian system can occur. In the vicinity of a singularity (DP point) in a conventional optical Hermitian system, the splitting of the eigenfrequency is directly proportional to the perturbation. However, near an Nth-order EP point where N eigenvalues ​​and eigenvectors are degenerate, the splitting of the eigenfrequency is directly proportional to the perturbation ξ. 1 / N Proportional. Therefore, for a sufficiently small perturbation (ξ << 1), the eigenfrequency splits more significantly near the EP point compared to the DP point. The higher the order of the EP point, the more pronounced the eigenfrequency split, meaning the more sensitive the eigenfrequency response to perturbations. A linearly polarized Laguerre Gaussian beam and a single-particle optical system can achieve the EP point ( Figure 4 ).

[0069] A Laguerre-Gaussian beam with a wavelength of 1.064 μm is used. Green represents a half-wave plate used to adjust the polarization state of the incident light, gray is a focusing lens with an adjustable numerical aperture, and orange is a glass slide on which the particles are placed for differentiation. The entire apparatus is placed in air.

[0070] The specific steps are as follows:

[0071] (1) According to Newton's second law, the total force on a particle in a light field can be written as:

[0072]

[0073] in, Let represent the force matrix, and γ represent the damping coefficient of the surrounding environment. In a plane perpendicular to the light propagation plane, the force matrix can be written as...

[0074]

[0075] Using the force matrix, the eigenvalues ​​of the force matrix under linearly polarized Laguerre-Gaussian beams are numerically calculated. Figure 4 (a) shows the change of the imaginary part of the force matrix eigenvalues ​​over time. The point where the imaginary part changes from 0 to non-zero is the Ep point. As shown in 4(b), calculate its phase diagram and the air resistance experienced by particles of different radii in the air (line 1). The air resistance experienced by particles with different radii is also different (line 1). Only particles located below curve 2 and above line 1 (air resistance coefficient) can be captured in the beam and are in motion. [13-14] It can be seen that near 0.44 μm, the eigenvalues ​​of the force matrix change from real to complex. This point is the EP point. Near this point, the response to perturbations is very sensitive. When the radius of the particle changes slightly, the final trajectory of the particle will change significantly. Therefore, we use polystyrene spheres with a radius of about 0.443 μm for simulation.

[0076] (2) Activate the two counter-propagating Laguerre-Gaussian beam emission modules with an orbital angular momentum of 1 (the two Laguerre-Gaussian beam emission modules are set up completely opposite to each other);

[0077] (3) Adjust the polarization component to make the Laguerre-Gaussian beam linearly polarized;

[0078] (4) When polystyrene microspheres (in solid state) are placed in a light field, under the radiation pressure of the vortex field, the polystyrene microspheres will rotate and the trajectory is an ellipse. Particles of different sizes have different motion trajectories.

[0079] (5) Continue irradiation with the Laguerre-Gaussian beam until the particle trajectories no longer change. Particles of similar size will have their major and minor axes coincide, but their semi-major and semi-minor axes will differ. By constructing a derived trajectory along the major axis, particles of different sizes can be filtered out. Figure 4 (d) It can be seen that near the EP point, when the particle radius changes from 0.443μm to 0.455μm, the radius changes by 0.002μm, but the semi-major axis of its corresponding orbital radius changes from 0.1μm to 0.37μm, which is nearly 4 times. Therefore, it is possible to accurately screen particles of similar size. Figure 4 (e) gives the trajectories of particles with different radii. Figure 4 (f) gives the distribution of optical force at different positions of a polystyrene sphere with a radius of 0.443 μm in the light field.

[0080] (6) Keep the radius of the ball constant at 0.4 μm and change the refractive index of the ball. Figure 5 (a) gives the change of the imaginary part of the eigenvalues ​​of the force matrix with the refractive index. Figure 5(b) It can be seen that when the refractive index changes from 3.07 to 3.25, the refractive index only changes by 0.2, but the semi-major axis of its trajectory changes from 0.1 μm to 0.35 μm, which is nearly 3.5 times. Therefore, it is possible to accurately screen particles with the same radius but similar refractive index.

[0081] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for precisely screening particles with subtle differences based on orbital tracking, characterized in that, It includes the following steps: (1) Using the force matrix, the eigenvalues ​​of the force matrix under linearly polarized Laguerre-Gaussian beams are calculated, and its Ep point is obtained; (2) Activate the two counter-propagating Laguerre-Gaussian beam emission modules with an orbital angular momentum of 1; (3) Adjust the polarization component to make the Laguerre-Gaussian beam linearly polarized; (4) Several micro-nano particles are placed in the light field, and the micro-nano particles rotate under the radiation pressure of the vortex field; the micro-nano particles are placed in the light field in solid form; (5) Maintain the illumination of the Laguerre-Gaussian beam until the trajectory of the micro-nano particles no longer changes, and filter out micro-nano particles of different sizes through the semi-major axis, wherein the absolute value of the radius difference between the micro-nano particles is ≤0.2μm; Alternatively, micro / nano particles with the same radius but different refractive indices can be screened out by their semi-major axis, wherein the absolute value of the refractive index difference between the micro / nano particles is ≤0.

5.

2. The method for precisely screening particles with subtle differences as described in claim 1, characterized in that, The micro / nano particles are polystyrene microspheres.

3. The method for precisely screening particles with subtle differences as described in claim 1, characterized in that, The absolute value of the radius difference between the micro and nano particles is ≤0.005μm.

4. The method for precisely screening particles with subtle differences as described in claim 1, characterized in that, The method for precisely screening particles with subtle differences employs a particle size sorting device based on orbital tracking of micro / nano particles, the particle size sorting device comprising: (1) Sample stage, used to place the micro-nano particles to be separated; (2) Laguerre-Gaussian beam emitting module one, used to emit Laguerre-Gaussian beams; Polarization adjustment component one, used to adjust the polarization direction of the Laguerre-Gaussian beam; One beam processing component is used to focus the Laguerre-Gaussian beam, which has been processed by the polarization adjustment component, to the micrometer level. The Laguerre-Gaussian beam emitting module, the polarization adjustment component, the spot processing component, and the sample stage are arranged in sequence. (3) Laguerre-Gaussian beam emission module two, used to emit Laguerre-Gaussian beams; Polarization adjustment component two is used to adjust the polarization direction of the Laguerre-Gaussian beam; The second beam processing component is used to focus the Laguerre-Gaussian beam processed by the polarization adjustment component to the micrometer level; The sample stage, the second light spot processing component, the second polarization adjustment component, and the second Laguerre-Gaussian beam emission module are arranged in sequence. The beam emitted by the first Laguerre-Gaussian beam emitting module and the beam emitted by the second Laguerre-Gaussian beam emitting module are beams that propagate in opposite directions. The first Laguerre-Gaussian beam emitting module and the second Laguerre-Gaussian beam emitting module are arranged opposite to each other.

Images