CN111979110A - Micro-target screening device based on multi-needle array vibration excitation fluid - Google Patents
Micro-target screening device based on multi-needle array vibration excitation fluid Download PDFInfo
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Abstract
The invention provides a micro-target screening device based on multi-needle array vibration exciting fluid, which forms a specific flow field in a liquid environment by the common vibration of a plurality of vibration generators and drives different micro-targets to pass through the flow field along different paths, thereby realizing the screening of the micro-targets; therefore, the method can realize the non-destructive screening of the cells, can obviously improve the efficiency of micro-target screening, is easy to realize automation, and reduces the cost of micro-target screening; compared with the existing micro-target screening mode, the method can obviously improve the experimental efficiency and reduce the experimental operation cost in the life science research field related to micro-target screening, has wide application prospect, and is expected to have good economic benefit in the life science research field and the industry field.
Description
Technical Field
The invention belongs to the technical field of micro-nano operation, and particularly relates to a micro-target screening device based on multi-needle array vibration excitation fluid.
Background
With the rapid development of micro-nano technology, the attention of the current society to micro-operation gradually rises. Whether it is the in vitro fertilization in clinical medicine, the cloning technology in biological research, or the three-dimensional observation of cells in medical research, it is necessary to screen out the cells that best meet the current experimental conditions according to the physical properties of the individual cells.
The current screening operation for a minute spherical object is mainly classified into a contact operation and a non-contact operation. The contact type operation takes a contact type mechanical arm as a main mode, and because the micro control of the contact type mechanical arm directly operates a biological target, the contact type operation has the characteristics of high precision, high flexibility, high repeatability and the like. However, the handling of such contact manipulators significantly increases the risk of cell damage, thereby increasing the potential operating costs. The most common non-contact operation at present is to perform non-contact control on cells in a closed environment through a microfluidic chip, so that the physiological properties of the cells are ensured. However, this method requires designing different microfluidic chips for different operation targets or operation tasks, thereby increasing operation cost and operation difficulty.
Therefore, the current technology cannot rapidly and nondestructively screen the micro-objects, and a new device and method are needed to improve the safety and efficiency of screening the micro-objects.
Disclosure of Invention
In order to solve the problem that the micro-target can not be screened quickly and nondestructively in the prior art, the invention provides a micro-target screening device based on multi-needle array vibration excitation fluid, which can meet the requirements of safety and high efficiency of cell screening.
A micro-object screening device based on multi-needle array vibration excitation fluid comprises a three-degree-of-freedom operation platform 1, a manual displacement platform 2, a metal array plate 3, an electron microscope 7, a glass slide 8, a processing unit and more than three vibration units, wherein each vibration unit comprises a metal connecting piece 4, a vibration generator 5 and a glass needle 6;
the metal array plate 3 is fixed on the manual displacement table 2; one end of the vibration generator 5 is fixedly connected to the metal array plate 3 through the metal connecting piece 4, the other end of the vibration generator is used for installing the glass needles 6, and meanwhile, the tail ends of the needle points of all the glass needles 6 are positioned on the same plane and are all positioned in a liquid environment on the glass slide 8;
the manual displacement platform 2 is fixed on the three-degree-of-freedom operation platform 1, wherein the three-degree-of-freedom operation platform 1 is used for adjusting the position of the manual displacement platform 2;
the vibration generator 5 is used for generating vibration under the control of an externally input sinusoidal voltage signal, so that the needle point vibration track of the glass needle 6 is circular;
the glass needle 6 is used for forming a vortex in a liquid environment through self vibration so as to drive the micro-target 12 in the liquid environment to move, wherein the moving direction of the micro-target 12 is the same as the direction of the sum of flow velocity vectors of all vortex fields at the position of the micro-target 12;
the electron microscope 7 is used for acquiring a flow field image in a liquid environment;
the processing unit is used for acquiring the size and the direction of the moving speed of the micro-object 12 according to at least five continuous frame flow field images, and then adjusting the sinusoidal voltage signal according to the size and the direction of the moving speed of the micro-object 12, so that the micro-object 12 moves along a preset track according to the preset speed, and the micro-object 12 is screened.
Further, the vibration generator 5 includes a metal rod 9 and a piezoelectric actuator 10;
the metal rod 9 and the glass needle 6 are respectively connected to two ends of the piezoelectric actuator 10, and meanwhile, the other end of the metal rod 9 is fixedly connected to the metal array plate 3 through the metal connecting piece 4; the piezoelectric actuator 10 is used to generate vibration under the control of an externally input sinusoidal voltage signal.
Further, the vibration generator 5 further comprises a glass needle connector 11, and the glass needle 6 is connected with the piezoelectric actuator 10 through the glass needle connector 11.
Further, the metal rod 9 and the glass needle 6 are vertically connected to both ends of the piezoelectric actuator 10, respectively.
Furthermore, the number of the vibration units is three, the needle points of the three glass needles form an equilateral triangle, and the three glass needles are respectively marked as a first glass needle, a second glass needle and a third glass needle;
assuming that the micro-object 12 is located between the needle tips of the first and second glass needles and the predetermined trajectory is a channel formed between the needle tips of the first and third glass needles, the processing unit adjusts phases of sinusoidal voltage signals input to the three vibration generators such that a direction of eddy current formed by the first vibration unit is clockwise, a direction of eddy current formed by the second vibration unit is counterclockwise, and a direction of eddy current formed by the third vibration unit is counterclockwise.
Furthermore, the number of the vibration units is three, the needle points of the three glass needles form an equilateral triangle, and the three glass needles are respectively marked as a first glass needle, a second glass needle and a third glass needle;
assuming that the micro-object 12 is located between the needle tips of the first and second glass needles and the predetermined trajectory is a channel formed between the needle tips of the second and third glass needles, the processing unit adjusts phases of sinusoidal voltage signals input to the three vibration generators such that a direction of eddy current formed by the first vibration unit is clockwise, a direction of eddy current formed by the second vibration unit is counterclockwise, and a direction of eddy current formed by the third vibration unit is clockwise.
Furthermore, the number of the vibration units is four, the needle points of the four glass needles form a square, and meanwhile, the four glass needles are respectively marked as a first glass needle, a second glass needle, a third glass needle and a fourth glass needle along the clockwise direction;
assuming that the micro-object 12 is located between the needle tips of the first and second glass needles and the predetermined trajectory is a channel formed between the needle tips of the third and fourth glass needles, the processing unit adjusts phases of sinusoidal voltage signals input to the four vibration generators such that the directions of eddy currents formed by the first and fourth vibration units are both clockwise and the directions of eddy currents formed by the second and third vibration units are both counterclockwise.
Furthermore, the number of the vibration units is four, the needle points of the four glass needles form a square, and meanwhile, the four glass needles are respectively marked as a first glass needle, a second glass needle, a third glass needle and a fourth glass needle along the clockwise direction;
assuming that the micro-object 12 is located between the needle tips of the first and second glass needles and the predetermined trajectory is a channel formed between the needle tips of the first and fourth glass needles, the processing unit adjusts phases of sinusoidal voltage signals input to the four vibration generators such that a direction of a vortex formed by the first vibration unit is clockwise, a direction of a vortex of a stroke of the second vibration unit is counterclockwise, the third vibration unit remains stationary, and a direction of a vortex formed by the fourth vibration unit is counterclockwise.
Furthermore, the number of the vibration units is four, the needle points of the four glass needles form a square, and meanwhile, the four glass needles are respectively marked as a first glass needle, a second glass needle, a third glass needle and a fourth glass needle along the clockwise direction;
assuming that the micro-object 12 is located between the needle tips of the first and second glass needles and the predetermined trajectory is a channel formed between the needle tips of the second and third glass needles, the processing unit adjusts phases of sinusoidal voltage signals input to the four vibration generators such that a direction of eddy current formed by the first vibration unit is clockwise, a direction of eddy current formed by the stroke of the second vibration unit is counterclockwise, a direction of eddy current formed by the third vibration unit is clockwise, and the fourth vibration unit remains stationary.
Further, the method for adjusting the sinusoidal voltage signal by the processing unit according to the magnitude and direction of the moving speed of the micro-object 12 specifically includes:
s1: continuously reading at least five frames of flow field images, and acquiring the size and the direction of the moving speed of the micro-object 12 according to the displacement of the micro-object 12 in the adjacent flow field images;
s2: judging whether the moving speed of the micro-object 12 is higher than the expected speed range or lower than the expected speed range, if so, reducing the peak-to-peak value of the sinusoidal voltage signal input to each vibration generator 5 at the same time, and returning to the step S1; if the speed is lower than the expected speed range, simultaneously increasing the peak-to-peak value of the sinusoidal voltage signal input to each vibration generator 5, and returning to step S1; if the speed is within the expected speed range, go to step S3;
s3: judging whether the moving speed direction of the micro-target 12 deviates from a preset track, if so, determining the vibration generator 5 closest to the micro-target 12, reducing the peak-to-peak value of the sinusoidal voltage signal input into the vibration generator 5, and simultaneously returning to the step S1; if not, the flow proceeds to step S4;
s4: and judging whether the current position of the micro-object 12 reaches the end point of the preset track, if not, reading the continuous at least five frames of flow field images again, and repeating the steps S1-S3 until the micro-object 12 reaches the end point of the preset track.
Has the advantages that:
the invention provides a micro-target screening device based on multi-needle array vibration exciting fluid, which forms a specific flow field in a liquid environment by the common vibration of a plurality of vibration generators and drives different micro-targets to pass through the flow field along different paths, thereby realizing the screening of the micro-targets; therefore, the method can realize the non-destructive screening of the cells, can obviously improve the efficiency of micro-target screening, is easy to realize automation, and reduces the cost of micro-target screening; compared with the existing micro-target screening mode, the method can obviously improve the experimental efficiency and reduce the experimental operation cost in the life science research field related to micro-target screening, has wide application prospect, and is expected to have good economic benefit in the life science research field and the industry field.
Drawings
FIG. 1 is a schematic structural diagram of a micro-object screening device based on multi-needle array vibration-excited fluid provided by the present invention;
FIG. 2 is a schematic structural diagram of a vibration generator provided in the present invention;
FIG. 3 is a schematic diagram illustrating the principle of rotating micro-objects of a micro-object screening apparatus based on multi-needle array vibration-excited fluid provided by the present invention;
FIG. 4 is a schematic diagram of a micro-object screening apparatus for binary screening of micro-objects based on multi-pin array vibration-excited fluid according to the present invention when the number of the vibration units is three;
FIG. 5 is a schematic diagram of another apparatus for screening micro-objects based on a multi-pin array vibration-excited fluid according to the present invention, which is used for screening micro-objects in two branches when the number of the vibration units is three;
FIG. 6 is a schematic diagram of a micro-object screening apparatus for three-way screening of micro-objects based on multi-needle array vibration exciting fluid when the number of the vibrating units is four according to the present invention;
FIG. 7 is a schematic diagram of a micro-object screening apparatus for three-way screening of micro-objects based on multi-needle array vibration exciting fluid according to another embodiment of the present invention when the number of the vibrating units is four;
FIG. 8 is a schematic diagram of a micro-object screening apparatus for three-way screening of micro-objects based on multi-needle array vibration exciting fluid according to the present invention when the number of the vibrating units is four;
FIG. 9 is a flow chart of a method for adjusting the sinusoidal voltage signal according to the magnitude and direction of the moving speed of the micro-object by the processing unit according to the present invention;
the device comprises a 1-three-degree-of-freedom operation platform, a 2-manual displacement platform, a 3-metal array plate, a 4-metal connecting piece, a 5-vibration generator, a 6-glass needle, a 7-electron microscope, an 8-glass slide, a 9-metal rod, a 10-piezoelectric actuator, a 11-glass needle connecting piece, a 12-micro target, a 13-eddy current field I, a 14-eddy current field II, a 15-eddy current field III, a 16-eddy current field IV, a 17-micro target inlet groove and a 18-micro target outlet groove.
Detailed Description
In order to make the technical solutions better understood by those skilled in the art, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application.
Referring to fig. 1, the figure is a schematic structural diagram of a micro-object screening apparatus based on multi-needle array vibration-excited fluid according to an embodiment of the present invention.
A micro-object screening device based on multi-needle array vibration excitation fluid is characterized by comprising a three-degree-of-freedom operating platform 1, a manual displacement table 2, a metal array plate 3, an electron microscope 7, a glass slide 8, a processing unit and more than three vibration units, wherein each vibration unit comprises a metal connecting piece 4, a vibration generator 5 and a glass needle 6.
The metal array plate 3 is fixed on the manual displacement table 2; one end of the vibration generator 5 is fixedly connected to the metal array plate 3 through the metal connecting piece 4, the other end of the vibration generator is used for installing the glass needles 6, and meanwhile, the tail ends of the needle points of all the glass needles 6 are located on the same plane and are all located in a liquid environment on the glass slide 8.
The manual displacement platform 2 is fixed on the three-degree-of-freedom operation platform 1, wherein the three-degree-of-freedom operation platform 1 is used for adjusting the position of the manual displacement platform 2. It should be noted that linear stepping motors are installed in three directions of the three-degree-of-freedom operating platform 1, and by moving the three-degree-of-freedom operating platform 1 in the three directions, the overall displacement of the vibrating array body can be realized, so as to drive the tip end of the glass needle 6 to move.
The vibration generator 5 is used for generating vibration under the control of an externally input sinusoidal voltage signal, so that the needle point vibration track of the glass needle 6 is circular.
The glass needle 6 is used for forming a vortex in a liquid environment through self vibration, so that the micro-target 12 in the liquid environment is driven to move, wherein the moving direction of the micro-target 12 is the same as the direction of the sum of flow velocity vectors of all vortex fields at the position of the micro-target 12.
The electron microscope 7 is used for acquiring a flow field image in a liquid environment so as to observe and feed back an experimental effect;
the processing unit is used for acquiring the size and the direction of the moving speed of the micro-object 12 according to at least five continuous frame flow field images, and then adjusting the sinusoidal voltage signal according to the size and the direction of the moving speed of the micro-object 12, so that the micro-object 12 moves along a preset track according to the preset speed, and the micro-object 12 is screened.
It should be noted that the linear stepping motor and the piezoelectric actuator 10 can be controlled by any suitable control device in the prior art, such as a general-purpose central processing unit, a microcontroller MCU, a field programmable device FPGA, a programmable logic controller PLC, and a special integrated circuit ASIC.
Referring to fig. 2, the figure is a schematic structural diagram of a vibration generator according to an embodiment of the present invention. The vibration generator 5 comprises a metal rod 9, a piezoelectric actuator 10 and a glass needle connector 11; the glass needle 6 is connected with one end of a piezoelectric actuator 10 through a glass needle connecting piece 11, the other end of the piezoelectric actuator 10 is connected with a metal rod 9, and meanwhile, the other end of the metal rod 9 is fixedly connected on the metal array plate 3 through a metal connecting piece 4.
It should be noted that the piezoelectric actuator 10 converts the input voltage signal into mechanical displacement, so as to drive the tip end of the glass needle 6 to move; when a sinusoidal voltage signal is input to the piezoelectric actuator 10, the tip end movement locus of the glass needle 6 may take a specific shape, and is generally circular; in addition, since the metal array plate 3, the metal connecting member 4, the vibration generator 5, and the glass needles 6 form a vibration array body by being connected to each other, the pitch of the glass needles 6 can be adjusted by changing the hole pitch of the metal array plate 3; meanwhile, since the plurality of vibration generators 5 are independent of each other, the movement trajectories of the tip ends of the plurality of glass needles 6 are also independent of each other.
It should be noted that the sinusoidal voltage signal causes the piezoelectric actuator 10 and the metal rod 9 to resonate. Since the displacement of the glass needle 6 vibration is actually the vector sum of the displacement of the metal rod 9 and the displacement of the piezoelectric actuator 10, the piezoelectric actuator 10 is perpendicularly connected to the glass needle 6 and the metal rod 3, respectively, so that it is convenient to control the vibration locus of the glass needle 6 to be circular.
Optionally, the length of the piezoelectric actuator adopted by the embodiment of the invention is 20mm, and the maximum displacement of the piezoelectric actuator is 17.2-17.6 μm; in other embodiments, piezoelectric actuators with other lengths and maximum displacements may be used, which is not described in detail in this embodiment.
The working principle of the micro-target screening device based on the multi-needle array vibration excitation fluid provided by the embodiment of the invention is as follows:
referring to fig. 3, the vibration generator 5 receives the control signal to drive the glass needles 6 to move respectively, the glass needle 6 in rotational motion drives the liquid around the needle tip to generate an eddy current field I13 along with the movement of the glass needle 6 in a liquid environment, the fluid movement direction of the eddy current field I13 is consistent with the movement direction of the glass needle 6, and the fluid movement speed of the eddy current field I13 increases along with the increase of the movement speed of the glass needle 6. When the micro-object 12 is in the eddy current field I13, the micro-object 12 will move along with the fluid moving direction of the eddy current field I13, i.e. the glass needle 6 end is used as the rotation axis to make circular motion, because the micro-object 12 is displaced by the drag force of the fluid.
It should be noted that, in order to avoid direct or indirect damage to the micro-object 12 and simultaneously prevent the glass needle 6 from directly contacting the slide glass 8 to damage the tip, the tip of the glass needle 6 of the present invention does not contact the micro-object 12 and needs to be kept at a certain distance from the upper surface of the slide glass 8, for example, the tip of the glass needle 6 is controlled to be raised by 50 μm in the vertical direction of the slide glass 8.
The working principle of the micro-target screening device based on multi-needle array vibration excitation fluid provided by the invention is further explained by taking three vibration units as examples:
referring to fig. 4, the figure is a schematic diagram of a micro-object screening device for binary screening of micro-objects based on multi-needle array vibration excitation fluid according to an embodiment of the present invention. The positions of the needle points of the three glass needles form an equilateral triangle, and the three glass needles are respectively marked as a first glass needle, a second glass needle and a third glass needle; assuming that the micro-object 12 is located between the needle tips of the first and second glass needles and the predetermined trajectory is a channel formed between the needle tips of the first and third glass needles, the processing unit adjusts phases of sinusoidal voltage signals input to the three vibration generators such that a direction of eddy current formed by the first vibration unit is clockwise, a direction of eddy current formed by the second vibration unit is counterclockwise, and a direction of eddy current formed by the third vibration unit is counterclockwise.
It should be noted that, if two eddy current directions are opposite to each other, it is sufficient to ensure that the phases of the sinusoidal voltage signals input to the two vibration generators are different by 180 °, for example, as shown in fig. 4, the phases of the positive line voltage signals input to the second vibration generator and the third vibration generator are the same, and the phase of the sinusoidal voltage signal input to the first vibration generator is different by 180 ° from the phase of the sinusoidal voltage signal input to the second vibration generator.
Further, as shown in fig. 4, a is the micro-object inlet slot 17, B, C, D is the micro-object outlet slot 18, and the micro-object inlet slot 17 and the micro-object outlet slot 18 are directly engraved on the slide 8; vortex field I13 is a clockwise vortex, vortex field II14 is a counter-clockwise vortex, and vortex field III15 is a counter-clockwise vortex. Wherein, the rotation direction of 3 glass needles 6 keeps unanimous with vortex field rotation direction respectively, and 3 glass needles 6's rotational speed size is the same. Since the sum of the flow velocity vectors of the 3 eddy current fields at the micro-object 12 is directed from the inlet slot a to the outlet slot B, the micro-object 12 moves in a straight-line trajectory from the inlet slot a to the outlet slot B through the flow field under the action of the fluid drag force.
Similarly, as shown in fig. 5, assuming that the micro-object 12 is located between the tips of the first and second glass needles and the predetermined trajectory is a channel formed between the tips of the second and third glass needles, the eddy current field I13 is a clockwise eddy current, the eddy current field II14 is a counterclockwise eddy current, and the eddy current field III15 is a clockwise eddy current. Wherein, the rotation direction of 3 glass needles 6 keeps unanimous with vortex field rotation direction respectively, and the rotational speed size of glass needle 6 is the same. Since the sum of the flow velocity vectors of the three eddy current fields at the micro-object 12 is directed from the inlet slot a to the outlet slot C, the micro-object 12 moves along an arc-shaped trajectory from the inlet slot a to the outlet slot C through the flow field under the action of the fluid drag force.
The working principle of the micro-target screening device based on multi-needle array vibration excitation fluid provided by the invention is further explained by taking four vibration units as an example:
referring to fig. 6, the figure is a schematic diagram of a three-way micro-object screening device for three-way micro-object screening based on multi-needle array vibration-excited fluid according to an embodiment of the present invention. The positions of the needle points of the four glass needles form a square, and meanwhile, the four glass needles are respectively marked as a first glass needle, a second glass needle, a third glass needle and a fourth glass needle along the clockwise direction; assuming that the micro-object 12 is located between the needle tips of the first and second glass needles and the predetermined trajectory is a channel formed between the needle tips of the third and fourth glass needles, the processing unit adjusts phases of sinusoidal voltage signals input to the four vibration generators such that the directions of eddy currents formed by the first and fourth vibration units are both clockwise and the directions of eddy currents formed by the second and third vibration units are both counterclockwise.
Further, as shown in fig. 6, a is the micro-object inlet tank 17, B, C, D is the micro-object outlet tank 18, and the micro-object inlet tank 17 and the micro-object outlet tank 18 are directly engraved on the slide 7. Vortex field I13 is a clockwise vortex, vortex field II14 is a counter-clockwise vortex, and vortex field III15 is a counter-clockwise vortex. The rotating directions of the glass needles 6 are respectively consistent with the rotating direction of the eddy current field, and the rotating speeds of the 4 glass needles 6 are the same. Since the sum of the flow velocity vectors of the 4 vortex fields at the micro-object 12 is directed from the inlet slot a to the outlet slot B, the micro-object 12 moves in a straight-line trajectory from the inlet slot a to the outlet slot B through the flow field under the action of the fluid drag force.
Similarly, as shown in fig. 7, assuming that the micro-object 12 is located between the tips of the first and second glass needles and the predetermined trajectory is a channel formed between the tips of the first and fourth glass needles, the eddy current field I13 is a clockwise eddy current, the eddy current field II14 is a counterclockwise eddy current, and the eddy current field III15 is a counterclockwise eddy current. The glass needle 6 at the vortex field IV16 is static, the rotating directions of the other three glass needles 6 are respectively consistent with the rotating direction of the vortex field, and the rotating speeds of the glass needles 6 are the same. Since the sum of the flow velocity vectors of the three eddy current fields at the micro-object 12 is directed from the inlet slot a to the outlet slot C, the micro-object 12 moves along an arc-shaped trajectory from the inlet slot a to the outlet slot C through the flow field under the action of the fluid drag force.
Assuming that the micro-object 12 is positioned between the tips of the first and second glass needles and the predetermined trajectory is a channel formed between the tips of the second and third glass needles as shown in fig. 8, the eddy current field I13 is a clockwise eddy current, the eddy current field II14 is a counterclockwise eddy current, and the eddy current field IV16 is a clockwise eddy current. The glass needle 6 at the vortex field III15 is static, the rotating directions of the other three glass needles 6 are respectively consistent with the rotating direction of the vortex field, and the rotating speeds of the glass needles 6 are the same. Since the sum of the flow velocity vectors of the 3 eddy current fields at the micro-object 12 is directed from the inlet slot a to the outlet slot D, the micro-object 12 moves along a circular arc-shaped trajectory from the inlet slot a to the outlet slot D through the flow field under the action of the fluid drag force.
Therefore, the shunting screening of the micro-objects 12 can be completed only by changing the rotating speed direction and the rotating speed of the glass needles 6 in the multi-needle array in the embodiment of the invention, so that the micro-objects 12 respectively enter different outlet grooves along different paths, the purpose of non-damage rapid screening of different micro-objects 12 is realized, and the screening of N-1 micro-objects can be realized by N more than or equal to 3 vibrating units. In addition, in other embodiments, other numbers of vibration generators may also be used to implement screening of different types of micro-objects, which is not described in this embodiment.
It should be noted that, by adjusting the phase of the sinusoidal voltage signal input to each vibration generator 5, only the micro-object 12 can be determined to move in the channel formed between any two vibration units, that is, the inlet slot and the outlet slot of the micro-object 12 are determined, and in order to make the micro-object 12 move along the predetermined track according to the preset speed more accurately, the present invention provides a method for the processing unit to adjust the sinusoidal voltage signal according to the size and direction of the moving speed of the micro-object, as shown in fig. 9, which specifically includes the following steps:
s0: the sinusoidal voltage input signals of the N vibrating units are first initialized, such as: sinusoidal voltage frequency 200Hz, peak to peak 5V.
S1: and continuously reading and storing at least five frames of flow field images acquired by the electron microscope, and judging the moving speed of the micro-target by using the multi-frame images.
S2: setting the desired speed range of the micro-object 12, such as: 15-20 μm/S, judging whether the moving speed of the micro-target 12 is higher than the expected speed range or lower than the expected speed range, if so, reducing the peak-to-peak value of the input voltage of the N vibration units at the same time, and returning to S1; if the moving speed of the micro-target is lower than the expected speed range, simultaneously increasing the peak-to-peak values of the input voltages of the N vibration units, and returning to the step S1; if the moving speed of the micro-object is within the expected speed range, the following steps are continuously executed.
S3: setting a predetermined trajectory such as: when the micro-target is deviated from the predetermined trajectory and approaches the 1 st, 2 nd, … th vibrating elements, the peak-to-peak value of the input voltage of the kth vibrating element is decreased, and the process returns to S1. If the position of the micro-object is within the predetermined track range, the following steps are continuously executed.
S4: judging whether the position of the micro-target reaches the outlet groove, if not, returning to the step S1; and if the micro-target reaches the outlet slot, disconnecting the sinusoidal voltage input signals of the N vibration units and ending.
Therefore, when the glass needle 6 rotates in a liquid environment, surrounding liquid can be caused to form an eddy current field, so that the micro-target 12 is driven to do circular motion along the fluid motion direction of the eddy current field by taking the glass needle 6 as a rotating shaft, and a plurality of eddy current fields are generated by vibrating the array body, and therefore non-damage rapid screening of different micro-targets 12 is achieved. Compared with the existing method for screening the micro-target 12 in a contact mode by utilizing the micro-nano manipulator or screening the micro-target in the micro-fluidic chip, the method provided by the invention realizes non-destructive cell screening in the experimental process, simplifies the screening process and reduces the operation difficulty of the experiment. In addition, the invention can adapt to the screening of different micro-objects 12 or different types by changing the number of the vibration generators 5 and the glass needles 6 or changing the hole spacing of the metal array plate 3, and has strong flexibility.
The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof, and it will be understood by those skilled in the art that various changes and modifications may be made herein without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (10)
1. A micro-object screening device based on multi-needle array vibration excitation fluid is characterized by comprising a three-degree-of-freedom operation platform (1), a manual displacement table (2), a metal array plate (3), an electron microscope (7), a glass slide (8), a processing unit and more than three vibration units, wherein each vibration unit comprises a metal connecting piece (4), a vibration generator (5) and a glass needle (6);
the metal array plate (3) is fixed on the manual displacement table (2); one end of the vibration generator (5) is fixedly connected to the metal array plate (3) through a metal connecting piece (4), the other end of the vibration generator is used for mounting the glass needles (6), and meanwhile, the tail ends of the needle points of all the glass needles (6) are positioned on the same plane and are all positioned in a liquid environment on the glass slide (8);
the manual displacement platform (2) is fixed on the three-degree-of-freedom operation platform (1), wherein the three-degree-of-freedom operation platform (1) is used for adjusting the position of the manual displacement platform (2);
the vibration generator (5) is used for generating vibration under the control of an externally input sinusoidal voltage signal, so that the needle point vibration track of the glass needle (6) is circular;
the glass needle (6) is used for forming a vortex in a liquid environment through self vibration so as to drive the micro target (12) located in the liquid environment to move, wherein the moving direction of the micro target (12) is the same as the direction of the sum of flow velocity vectors of all vortex fields at the position of the micro target;
the electron microscope (7) is used for acquiring a flow field image in a liquid environment;
the processing unit is used for acquiring the size and the direction of the moving speed of the micro-object (12) according to at least five continuous frame flow field images, and then adjusting the sinusoidal voltage signal according to the size and the direction of the moving speed of the micro-object (12), so that the micro-object (12) moves along a preset track according to the preset speed, and the micro-object (12) is screened.
2. The micro-object screening device based on multi-needle array vibration exciting fluid is characterized in that the vibration generator (5) comprises a metal rod (9) and a piezoelectric actuator (10);
the metal rod (9) and the glass needle (6) are respectively connected to two ends of the piezoelectric actuator (10), and meanwhile, the other end of the metal rod (9) is fixedly connected to the metal array plate (3) through the metal connecting piece (4); the piezoelectric actuator (10) is used for generating vibration under the control of an externally input sinusoidal voltage signal.
3. The micro-object screening device based on multi-needle array vibration-excited fluid is characterized in that the vibration generator (5) further comprises a glass needle connector (11), and the glass needle (6) is connected with the piezoelectric actuator (10) through the glass needle connector (11).
4. The micro-object screening device based on multi-needle array vibration exciting fluid is characterized in that the metal rod (9) and the glass needle (6) are respectively and vertically connected to two ends of the piezoelectric actuator (10).
5. The micro-object screening device based on multi-needle array vibration-excited fluid as claimed in claim 1, wherein the number of the vibration units is three, and the needle points of the three glass needles are located to form an equilateral triangle, and at the same time, the three glass needles are respectively marked as a first glass needle, a second glass needle and a third glass needle;
assuming that the micro-object (12) is located between the needle tips of the first and second glass needles and the predetermined trajectory is a channel formed between the needle tips of the first and third glass needles, the processing unit adjusts phases of sinusoidal voltage signals input to the three vibration generators such that a direction of eddy current formed by the first vibration unit is clockwise, a direction of eddy current formed by the second vibration unit is counterclockwise, and a direction of eddy current formed by the third vibration unit is counterclockwise.
6. The micro-object screening device based on multi-needle array vibration-excited fluid as claimed in claim 1, wherein the number of the vibration units is three, and the needle points of the three glass needles are located to form an equilateral triangle, and at the same time, the three glass needles are respectively marked as a first glass needle, a second glass needle and a third glass needle;
assuming that the micro-object (12) is located between the needle tips of the first and second glass needles and the predetermined trajectory is a channel formed between the needle tips of the second and third glass needles, the processing unit adjusts phases of sinusoidal voltage signals input to the three vibration generators such that a direction of eddy current formed by the first vibration unit is clockwise, a direction of eddy current formed by the second vibration unit is counterclockwise, and a direction of eddy current formed by the third vibration unit is clockwise.
7. The micro-object screening device based on the multi-needle array vibration excitation fluid as claimed in claim 1, wherein the number of the vibration units is four, and the needle points of the four glass needles are located to form a square, and meanwhile, the four glass needles are respectively marked as a first glass needle, a second glass needle, a third glass needle and a fourth glass needle along the clockwise direction;
assuming that the micro-object (12) is positioned between the needle tips of the first and second glass needles and the predetermined trajectory is a channel formed between the needle tips of the third and fourth glass needles, the processing unit adjusts phases of sinusoidal voltage signals input to the four vibration generators such that the directions of eddy currents formed by the first and fourth vibration units are both clockwise and the directions of eddy currents formed by the second and third vibration units are both counterclockwise.
8. The micro-object screening device based on the multi-needle array vibration excitation fluid as claimed in claim 1, wherein the number of the vibration units is four, and the needle points of the four glass needles are located to form a square, and meanwhile, the four glass needles are respectively marked as a first glass needle, a second glass needle, a third glass needle and a fourth glass needle along the clockwise direction;
assuming that the micro-object (12) is located between the needle tips of the first and second glass needles and the predetermined trajectory is a channel formed between the needle tips of the first and fourth glass needles, the processing unit adjusts phases of sinusoidal voltage signals input to the four vibration generators such that a direction of a vortex formed by the first vibration unit is clockwise, a direction of a vortex of a stroke of the second vibration unit is counterclockwise, the third vibration unit remains stationary, and a direction of a vortex formed by the fourth vibration unit is counterclockwise.
9. The micro-object screening device based on the multi-needle array vibration excitation fluid as claimed in claim 1, wherein the number of the vibration units is four, and the needle points of the four glass needles are located to form a square, and meanwhile, the four glass needles are respectively marked as a first glass needle, a second glass needle, a third glass needle and a fourth glass needle along the clockwise direction;
assuming that the micro-object (12) is located between the needle tips of the first and second glass needles and the predetermined trajectory is a channel formed between the needle tips of the second and third glass needles, the processing unit adjusts phases of sinusoidal voltage signals input to the four vibration generators such that a direction of eddy current formed by the first vibration unit is clockwise, a direction of eddy current formed by the stroke of the second vibration unit is counterclockwise, a direction of eddy current formed by the third vibration unit is clockwise, and the fourth vibration unit remains stationary.
10. The micro-object screening device based on multi-needle array vibration excitation fluid as claimed in claim 1, wherein the processing unit adjusts the sinusoidal voltage signal according to the magnitude and direction of the moving speed of the micro-object (12) by:
s1: continuously reading at least five frames of flow field images, and acquiring the size and the direction of the moving speed of the micro-object (12) according to the displacement of the micro-object (12) in the adjacent flow field images;
s2: judging whether the moving speed of the micro-target (12) is higher than the expected speed range or lower than the expected speed range, if so, reducing the peak-to-peak value of the sinusoidal voltage signal input into each vibration generator (5) at the same time, and returning to the step S1; if the speed is lower than the expected speed range, simultaneously increasing the peak-to-peak value of the sinusoidal voltage signals input into each vibration generator (5), and returning to the step S1; if the speed is within the expected speed range, go to step S3;
s3: judging whether the moving speed direction of the micro-target (12) deviates from a preset track, if so, determining the vibration generator (5) closest to the micro-target (12), reducing the peak-to-peak value of a sinusoidal voltage signal input into the vibration generator (5), and simultaneously returning to the step S1; if not, the flow proceeds to step S4;
s4: and judging whether the current position of the micro-object (12) reaches the end point of the preset track, if not, reading the continuous at least five frames of flow field images again, and repeating the steps S1-S3 until the micro-object (12) reaches the end point of the preset track.
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