CN117995450A - Particle manipulator based on photothermal waveguide - Google Patents

Abstract

The invention provides a particle manipulator based on a photo-thermal waveguide, which can interact with light to generate a local heat source through laser inscription and can be used for particle manipulation. The method mainly comprises the steps of exciting a local heat source on a photo-thermal waveguide (5) of a focused laser (1), wherein the waveguide has excellent photo-thermal conversion and control capability, long-distance thermal convection force and short-distance thermophoresis force acting on particles can be induced to be formed, and non-contact manipulation (7) of micro-nano particles (6) can be realized by utilizing a capture potential well (9) near the photo-thermal waveguide (5). The novel noninvasive micro-operation technology not only can minimize physical damage to a target object, but also can realize accurate manipulation of microscopic entities, and the manipulation mode brings new possibility for photo-thermal control of cells and biomolecules.

Description

Particle manipulator based on photothermal waveguide

(I) Technical field

The present invention provides a particle manipulator based on photothermal waveguide, which mainly relates to the fields of laser lithography, thermophoresis effect and fluid dynamics. More specifically, after the required photothermal waveguide is written with laser, the capture and manipulation of micro-nano particles is achieved near the photothermal waveguide through the interaction between the laser and the photothermal waveguide.

(II) Background technology

Low-damage, non-contact manipulation technology is of milestone significance and has been widely used in various fields such as biomedicine, microassembly, and chemical research. Since Ashikn first demonstrated the manipulation of particles by optical forces in the 1970s, its low-damage and non-contact manipulation characteristics have attracted widespread attention from researchers in many fields. In the realization of low-damage, non-contact manipulation technology, optical means play a vital role. Optical means mainly include optical potential wells formed by laser beams, light field control, etc. Through the optimization and innovation of optical means (such as converting light energy into heat energy and then manipulating particles), more extensive, more accurate, and more stable low-damage, non-contact manipulation can be achieved. Since then, there have been many similar technologies, including magnetic tweezers, cold tweezers, acoustofluidics, and microfluidics manipulation.

Directed self-assembly, especially of materials at the mesoscale, has attracted great interest in the scientific community due to the degree of control it offers in creating a chosen structure. As a result, it has fostered a variety of research of a highly interdisciplinary nature, with applications ranging from nanotechnology to microelectronics. In recent years, the photothermal effect of this special material has particularly attracted a lot of attention, while gaining considerable prominence due to the simplicity and flexibility of the process, its low cost, etc.

As the above technologies continue to develop, microfluidics has also made a qualitative leap. Since this technology directly manipulates the target object with the help of microflow, the damage to the target object is basically negligible. Unlike magnetic tweezers, this technology does not require magnetic particles and can act on any tiny particles without considering their physical properties. Compared with acoustic tweezers, it will not be affected by external interference, has a wider range of manipulation, and has high resolution. Microfluidics is an emerging technology that can control tiny flows such as liquids, gases or other substances. It uses electromagnetic, optical, chemical or mechanical effects at the micron scale to accurately control the flow of fluids at the micron scale, thereby achieving treatment, detection and analysis. Microfluidics has a wide range of applications in medical, environmental monitoring and biotechnology, and can achieve faster, more accurate and more effective detection and diagnosis. In recent years, microfluidics has received more and more attention, and researchers are constantly exploring the application of microfluidics in particle manipulation.

Photons and materials can achieve momentum transfer through the interaction of absorption, scattering, reflection and refraction. In most cases of interaction between photons and materials, energy transfer between photons and molecules is achieved through absorption, and the energy is released into the fluid in the form of a thermal gradient to generate a thermal convection field. The technique of manipulating particles by using a thermal convection field generated by a thermal gradient is also called thermal optical tweezers. It should be noted that as a low-damage non-contact operation, thermal optical tweezers not only have a large controllable range, but are also insensitive to the characteristics of the manipulated object and have no photothermal degradation. In 2020, Tatsuya Shoji et al. (Scientific Reports, 2020, 10(1): 3349) achieved the first permanent fixation of DNA on a plasma substrate, realizing size-dependent separation and fixation. This fixation is achieved by a combination of plasma-enhanced optical forces and thermophoretic forces induced by the thermophoretic effect. This technology provides a new way for the separation and fixation of DNA, and opens up new possibilities for the optical separation and fixation of proteins and other biomolecules. In 2021, Jingang Li et al. (Science Advances, 2021, 7(26): 1101) proposed a new type of tweezers "photocooling tweezers", which uses ytterbium-doped yttrium lithium fluoride (Yb:YLF) crystals and 1020nm lasers to achieve local laser cooling in liquid media. Based on the thermophoresis effect, particles and molecules can be stably captured in the cold zone generated by the laser, effectively avoiding photodamage and photoinvasiveness, and solving the problem that particles cannot be stably captured due to the positive Soret coefficient. In 2022, Joby et al. (Scientific Reports, 2022, 12(1): 3657) used 785nm low-intensity laser to irradiate graphene oxide, and used the unique photothermal properties of this material to form a strong temperature gradient, thereby achieving large-scale micro-nano assembly and aggregation, and then forming a 385nm silica microbead assembly. Moreover, this aggregation process is fast and reversible, and is caused by optically driven thermophoresis. This method has a wide range of application prospects and can be used to study non-equilibrium material assembly, surface-enhanced Raman scattering, and can also be used in the capture and photoablation of Escherichia coli.

The particle manipulator based on photothermal waveguide proposed in the present invention innovatively proposes photolithography material writing and photothermal flow control. The thermophoresis effect and thermal convection effect triggered by the photothermal effect can be used to flexibly and accurately capture and manipulate particles. It has the advantages of high manipulation accuracy, large capture range, no requirements on the properties of the manipulated material, and little damage. It can be used in nanotechnology, drug delivery, biomedicine and other fields.

(III) Summary of the invention

The purpose of the present invention is to provide a particle manipulator based on photothermal waveguide. Through photolithography of photothermal waveguide, the photothermal effect between light and photothermal waveguide generates thermophoresis and thermal convection, which affects the change of surrounding flow field, and can realize non-contact capture of micro-nano particles.

The object of the present invention is achieved in that:

The external device for particle manipulation based on photothermal waveguide is composed of a micron-level three-dimensional laser direct writing device, which is composed of a laser (201), a spatial light modulator (202), a reflector (203), a semi-transparent and semi-reflective mirror (204), an imaging lens (205), a CCD (206), an objective lens (207), a sample chamber (208) placed on a three-dimensional displacement stage, an LED lighting lamp (209), a laser-written photothermal waveguide patterning (210), and a particle capture diagram (211).

The manipulation system mainly focuses the laser (1) onto the bottom surface (4) of the sample chamber containing the photothermal waveguide, and adds a micro-nano particle solution (4) into the sample chamber (3). When the manipulation laser (8) interacts with the photothermal waveguide (5), a particle capture potential well will be generated near the photothermal waveguide (5), and the micro-nano particles (6) will be captured in the potential well. When the laser position (7) is changed, the particles will change accordingly, achieving a non-contact manipulation effect.

Characterized in that the manipulation laser (8) is a single laser beam, a dual laser combination or a plurality of laser beams. Characterized in that the manipulation laser (8) is Gaussian light, Bessel light, Airy light, annular light or other special light beams. Characterized in that the photolithography material (2) is a free radical photoinitiator, a cationic photoinitiator, a metal oxoate and other related photolithography writing materials. Characterized in that the micro-nano particles (6) are dielectric particles, metal particles, biological particles or particles of any other material. Characterized in that the micro-nano particles (6) are spherical particles, square particles, angular particles or particles of any other shape. Characterized in that the photothermal waveguide (7) is a point photothermal waveguide array, a strip photothermal waveguide array, a point and strip combination photothermal waveguide array or other patterned photothermal waveguide array.

The principle of the photothermal waveguide in the invented device for manipulating micro-nanoparticles is described in detail below.

The liquid around the photothermal waveguide will generate heat due to the interaction between light and the photothermal waveguide. The resulting temperature gradient will trigger the emergence of thermophoretic force and thermal convection force. The two forces are balanced to achieve particle capture.

In this study, the interaction between the self-assembled photothermal waveguide and the laser is characterized by selective absorption, and the absorbed optical power can be described by the following formula:

_Pa ＝ _NσabsI (1)

Where N is the number of particles under irradiation, I is the intensity of the incident laser, and σ _abs is the absorption cross-section coefficient, which is an area-dimensional physical quantity that refers to the probability that a particle (or particle system) interacts with a substance and is completely absorbed by the substance under certain conditions. According to the Joule effect, the absorbed light power is converted into heat.

When the laser is irradiated onto the photothermal waveguide structure, the light energy is absorbed and converted into the distribution of light intensity I:

where w(z) is the beam radius, and r and z are cylindrical coordinates.

The heat flux generated by light produces an inhomogeneous temperature gradient field T in the aqueous solution, so the interaction force drives the particles to move, which mainly includes thermophoretic force and fluid resistance:

Thermophoretic forces are applied to particles in an inhomogeneous heat flow. The driving mechanism behind this force is the collision of liquid molecules on the particle surface. Collisions are more likely to occur on the hotter side of the particle, where the average molecular velocity of the liquid is greater. This results in a net force towards the cooler regions of the liquid. In a continuous flow, the thermophoretic force is defined as:

where k _B is the Boltzmann constant, T is the fluid temperature, is the temperature gradient and _ST is the Soret coefficient. For PS particles, _ST is positive 18K ^-1 , which means that most particles will migrate towards the cooler region in the temperature gradient.

The opposing drag is caused by thermal convection as defined by Stokes' drag law:

in and/> are the fluid and particle velocities, respectively. m _p is the particle mass. The characteristic time scale for the acceleration of a particle due to Stokes drag is τ _p , which is given by:

where _ρp is the particle density, μ is the fluid dynamic viscosity, and _ρp is the particle radius.

From the two flow field distributions generated by the temperature gradient, it can be seen that the thermophoretic force is distributed near the heat source, and the thermal convection is distributed farther away. In terms of direction, if the thermophoretic force is positive, the corresponding convection force is just the opposite, and the two will reach equilibrium within a certain range of the heat source. The equilibrium point of the force is like a potential well, where the particle will be stable and captured. We flexibly change the laser to form a potential well change to achieve the manipulation of the particle.

The advantages of the present invention are mainly reflected in the proposal of a particle manipulator based on a photothermal waveguide. Due to the good photothermal conversion of laser light by the photothermal waveguide, this causes a non-isothermal temperature field and generates a drag force and a thermophoretic force acting on the particles. Through this non-contact force balance, the particles can be trapped in the capture potential well to avoid photothermal damage caused by direct contact, thus achieving particle manipulation around the waveguide, while the trajectory of the particles is precisely controlled by designing the form of the heat source. Our research results provide a new understanding of the manipulation of suspended particles in a non-isothermal temperature field, and they are also of great significance for biological applications involving systematic manipulation of particles. This technology can also be applied to the collection and removal of cancer cells, the sorting of bacteria and cells, the delivery of drug agents, the monitoring of tumor cell apoptosis processes, and the study of lung cancer cell resistance.

(IV) Description of the drawings

FIG1 is a schematic diagram of a particle manipulator based on a photothermal waveguide, the structure of which mainly includes a laser module (1), a sample chamber bottom surface (3), a micro-nano particle solution (4), a photothermal waveguide (5), micro-nano particles (6), etc.

FIG2 is a schematic diagram of the manufacture of an external device for manipulating micro-nanoparticles, which includes a laser (201), a spatial light modulator (202), a reflector (203), a semi-transparent and semi-reflective mirror (204), an imaging lens (205), a CCD (206), an objective lens (207), a sample chamber (208) placed on a three-dimensional displacement stage, an LED lighting lamp (209), a laser-engraved photothermal waveguide patterning (210), and a particle capture diagram (211).

FIG3 is a schematic diagram of the preparation of a photothermal waveguide and a laser particle manipulation diagram in a system for particle manipulation based on a photothermal waveguide. From top to bottom, the arrows point to the following order: first, the photolithography material is placed in a rectangular glass sample chamber, and then the structure of the photothermal waveguide is written in the photoresist using a micron-level three-dimensional laser direct writing device. Then, the structure left after the sample chamber is cleaned with deionized water is shown. Finally, a schematic diagram of the capture and manipulation of particles next to the photothermal waveguide structure is shown using a micron-level three-dimensional laser device.

Figure 4 is a schematic diagram of different photothermal waveguide structures, Figure 4(a) is a point-shaped photothermal waveguide array, Figure 4(b) is a circular photothermal waveguide array, Figure 4(c) is a strip-shaped photothermal waveguide array, Figure 4(d) is a zigzag-type photothermal waveguide array, Figure 4(e) is a point-shaped and strip-shaped combined photothermal waveguide array, and Figure 4(f) is a Z-shaped and point-shaped combined photothermal waveguide array.

Figure 5 is an optional type of transport photothermal waveguide array (409), Figure 5(a) is a point photothermal waveguide array, Figure 5(b) is a zigzag photothermal waveguide array, Figure 5(c) is a triangle photothermal waveguide array, and Figure 5(d) is a strip photothermal waveguide array.

Figure 6 is an optional sorting photothermal waveguide (409) type, Figure 6 (a) is a circular photothermal waveguide combination array, Figure 6 (b) is a square photothermal waveguide combination array, Figure 6 (c) is a circular photothermal waveguide combination array, and Figure 6 (d) is a polygonal photothermal waveguide combination array.

FIG7 is a system for particle manipulation, sorting and transport based on photothermal waveguides, the structure of which consists of a laser manipulation part (401), an imaging part (405), a host computer control part (406), and a microfluidic chip (403), wherein the microfluidic chip (403) is mainly composed of four microfluidic channels, namely a mixed solution channel (405) and a subsequent sorting channel (413).

(V) Specific implementation methods

In order to make the purpose, technical scheme and advantages of this application clearer, the present invention is further described below in conjunction with the accompanying drawings and embodiments, and the embodiments of the present invention include but are not limited to the following embodiments. Based on the embodiments of this application, all other embodiments obtained by ordinary technicians in this field without making creative work belong to the scope of protection of this application.

The present invention is further described below with reference to the accompanying drawings and examples.

As shown in Figures 1 and 2, the specific implementation scheme includes a solid laser (201), a spatial light modulator (202), a galvanometer (203), a semi-transparent and semi-reflective mirror (204), an imaging lens (205), a CCD (206), an objective lens (207), a sample chamber (208) placed on a three-dimensional translation stage, and an LED lighting lamp (209). The light beam emitted from the solid laser (201) enters the reflective spatial light modulator (202). The modulated light emitted from the reflective spatial light modulator (202) passes through the reflector (203) and then enters the high-focusing objective lens (207) through the semi-transparent and semi-reflective mirror (204). The laser (1) is focused onto the bottom surface (4) of the sample chamber containing the photothermal waveguide through the objective lens (207). A micro-nano particle solution (4) is added to the sample chamber (3). When the manipulation laser (8) interacts with the photothermal waveguide (5), a particle capture potential well is generated near the photothermal waveguide (5). The micro-nano particle (6) is captured in the potential well. When the laser position (7) is changed, the particle changes accordingly, thereby achieving a non-contact manipulation effect.

The device also has another imaging light path, which is mainly composed of an LED lighting lamp (209) and a CCD (206). The light from the LED lighting lamp (209) irradiates the sample chamber (208), passes through the sample chamber (208) to the objective lens (207) below, and then passes through a semi-transparent and semi-reflective mirror (204). The semi-transparent and semi-reflective mirror (204) has a high transmittance to green light and a high reflectance to red light, so the illumination light can be reflected by it to the CCD (206). We can see the patterned schematic diagram after self-assembly of the photolithographic material (210). At the same time, we can manipulate the particles through a simple photothermal waveguide (211), and we can clearly observe the capture movement of micro-nanoparticles during the experiment.

Based on the new photothermal waveguide, the sample preparation and particle manipulation process in the thermal optical tweezers system can be divided into the following steps:

Step 1: Preparation of photothermal waveguide (see Figure 3). A rectangular hollow glass sheet (301) is used to prepare the sample chamber, and then a solution (303) formed by a photoinitiator and water is dripped into the sample chamber just prepared. The photoinitiator solution (303) is self-assembled by focusing the laser (304). The laser will attract the surrounding photoinitiator particles (305) to gather toward the center of the laser (306). At this time, the laser (307) is moved for a certain period of time to form the photoinitiator waveguide structure (308) we need. Then, the sample chamber is re-washed with deionized water, leaving a sample manipulation chamber containing a photothermal waveguide.

Step 2: Then, the experimental environment is constructed. First, a solution of micro-nanoparticles is prepared. In this example, polystyrene particles and a deionized water solution are used to prepare the solution (309), which is then dripped into the sample chamber through a pipette.

Step 3: By using the built imaging equipment and laser manipulation equipment, we can focus the laser on the photothermal waveguide. When the focused laser irradiates the surface of the photothermal waveguide, thermophoresis and thermal convection will occur. At this time, the polystyrene balls in the solution will be captured near the photothermal waveguide (310). By manipulating the offset (312) of the laser (304), the flow field around the photothermal waveguide will change accordingly (311), and finally the manipulation of micro-nanoparticles near the photothermal waveguide can be achieved.

The present invention is further described below in conjunction with specific application implementation cases:

As shown in FIG7 , the structure of the case is composed of a laser manipulation part (401), an imaging part (405), a host computer control part (406), and a microfluidic chip (403). The laser manipulation part (401) is input into the objective lens (401) after the light field is controlled by the spatial light modulator. After being focused by the objective lens (401), a manipulation laser (402) is formed and sent to the microfluidic chip for particle manipulation. The microfluidic chip (403) is mainly composed of four microfluidic channels, namely the mixed solution channel (405) and the subsequent sorting channel (413). The free sorting and transport of particles occur in the connecting channel (414), which is mainly composed of a sorting photothermal waveguide structure (409) and a transport photothermal waveguide array (410).

The specific manipulation process is mainly to input a solution (408) containing three micro-nano particles of different sizes into the mixed solution channel (405). When the solution flows through the mixed solution channel (405) and reaches the sorting photothermal waveguide (409), a photo is taken by CCD (406) and transmitted to the computer (407). After the computer calculates and plans the path of the particle movement on the sorting photothermal waveguide structure (409), the spatial light modulator is controlled to generate multiple laser beams (411), and particles of different sizes are captured and moved respectively. The particles of different sizes are placed in different transport photothermal waveguide arrays (410), wherein the transport photothermal waveguide structure (410) transports different particles respectively. The manipulation laser (412) is controlled by the computer (407), and alternately moves on the photothermal waveguide array to transport particles of different sizes. Finally, the particles are transported to the corresponding microfluidic channels (413) to complete the particle capture and sorting manipulation.

Optionally, the sorting photothermal waveguide structure (409) can be a circular photothermal waveguide combination, a strip photothermal waveguide combination or a polygonal photothermal waveguide combination, as shown in FIG. 5 (a-d).

The transport photothermal waveguide array (410) can be a point photothermal waveguide array, a curved photothermal waveguide array, a strip photothermal waveguide array or a polygonal photothermal waveguide array, as shown in Figure 6 (a-d).

The above scheme of the embodiment of the present invention, as shown in FIG7, can construct a sorting module in a microfluidic channel by an optical method, and the particles to be sorted can be sorted by controlling the movement of light by a computer, which can realize non-contact capture, as well as continuous sorting and transportation functions; at the same time, the sorting effect depends on but is not limited to the refractive index properties and size and shape of the particles, and the method of the present invention can be used for effective sorting. In addition, the flow field effect of the laser on the photothermal waveguide is used to capture, sort and transport particles in a non-contact manner. Because there is no direct contact, the impact on biological cells is small, which is conducive to maintaining biological activity. At the same time, the precise capture of particles by the laser prevents the crowding problem of the microfluidic channel.

The above is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed in the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims (8)

1. A particle manipulator based on a photothermal waveguide, characterized in that the particle manipulator based on the photothermal waveguide mainly comprises: a laser module (1), a sample chamber (3), a particle solution (4) and a photothermal waveguide (5); the laser module (1) performs photolithography to convert the photolithographic material (2) into the photothermal waveguide (5) in the sample chamber (3); the photothermal waveguide (5) has photothermal conversion and control capabilities; when the micro-nano particle solution (4) is added to the sample chamber (3), the local temperature can be induced by manipulating the laser (8) Gradient, generating thermophoresis and thermal convection around the photothermal waveguide (5), the directions of the forces acting on the micro-nano particles (6) are opposite, thereby forming a capture potential well (9), and achieving the capture of the micro-nano particles (6) at the potential well equilibrium position; when the micro-nano particles are manipulated, the manipulation laser (8) is irradiated onto the photothermal waveguide (5), and when the manipulation laser (8) interacts with the photothermal waveguide (5) to successfully capture the micro-nano particles (6), the laser position (7) can be changed to achieve a non-contact and precise micro-nano particle (6) manipulation effect. 2. According to claim 1, the particle manipulator based on photothermal waveguide is characterized in that the photothermal waveguide (5) is prepared as follows: first, take the photolithography material, add pure water and stir, and obtain a solution after shaking; drip the previously prepared solution into the sample chamber, and then pass a focused laser to the bottom of the sample chamber. Under the action of the laser, the photolithography material will self-assemble under the action of the laser, and the required photothermal waveguide structure can be obtained by moving the laser; finally, the sample chamber is re-cleaned with deionized water, leaving a sample manipulation chamber containing the photothermal waveguide. 3. The particle manipulator based on photothermal waveguide according to claim 1 is characterized in that the manipulation laser (8) is a single-beam laser, a double-beam laser or a multi-beam laser. 4. The particle manipulator based on photothermal waveguide according to claim 1 is characterized in that the manipulation laser (8) is Gaussian light, Bessel light, Airy light, ring light or other special light beams. 5. The particle manipulator based on photothermal waveguide according to claim 1 is characterized in that the photolithography material (2) is a free radical photoinitiator, a cationic photoinitiator, a metal oxoate or other photolithography material. 6. The particle manipulator based on photothermal waveguide according to claim 1 is characterized in that the micro-nano particles (6) are dielectric particles, metal particles, biological particles or particles of any other material. 7. The particle manipulator based on photothermal waveguide according to claim 1 is characterized in that the micro-nano particles (6) are spherical particles, square particles, angular particles or particles of other arbitrary shapes. 8. The particle manipulator based on photothermal waveguide according to claim 1 is characterized in that the photothermal waveguide (7) is a point photothermal waveguide array, a strip photothermal waveguide array, a point and strip combined photothermal waveguide array or other patterned photothermal waveguide array.