CN115386487A - Single cell puncture system based on hammer type micro-nano robot - Google Patents

Single cell puncture system based on hammer type micro-nano robot Download PDF

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Publication number
CN115386487A
CN115386487A CN202210974703.9A CN202210974703A CN115386487A CN 115386487 A CN115386487 A CN 115386487A CN 202210974703 A CN202210974703 A CN 202210974703A CN 115386487 A CN115386487 A CN 115386487A
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hammer
type micro
nano robot
single cell
micro
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CN115386487B (en
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李隆球
庄仁诚
周德开
刘军民
岳红尔
王艺醇
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Harbin Institute of Technology
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Harbin Institute of Technology
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M35/00Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
    • C12M35/02Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
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    • C12M23/16Microfluidic devices; Capillary tubes
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    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
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    • C12M27/10Rotating vessel
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    • C12M35/00Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
    • C12M35/04Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli

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Abstract

The invention relates to a single cell puncturing technology, in particular to a hammer type micro-nano robot-based single cell puncturing system, which comprises a hammer type micro-nano robot, a magnetic field generating device and an ultrasonic field generating device, wherein the magnetic field generating device is used for driving the hammer type micro-nano robot to rotate, the ultrasonic field generating device is used for driving the hammer type micro-nano robot to move; the two physical field coupling effects can realize effective puncture breakthrough on the cell membrane of a single cell.

Description

Single cell puncture system based on hammer type micro-nano robot
Technical Field
The invention relates to a single cell puncturing technology, in particular to a single cell puncturing system based on a hammer type micro-nano robot.
Background
The single cell puncture technology is a key technical premise for research and application of clinical diagnosis, drug research and development, genetic engineering and the like. At present, single cell puncture mostly still stays at a manual operation level, and is realized by using a mechanical clamp, a micro-pipette, a puncture needle and the like. The existing method depends on experience and proficiency of operators to a great extent, is low in operation precision, high in failure rate and low in efficiency, and is difficult to meet the requirement of accurate puncture for single cells. The micro-nano robot is a micro-nano actuator with small scale, good controllability and large thrust-weight ratio, can realize accurate motion control and complex functions in a micro environment, and particularly has wide application prospect in the field of biomedicine. The efficient driving capability and flexible controllability of the micro-nano robot are utilized to serve as a micro-nano scale puncture needle to act on cell membranes of single cells, and effective puncture breakthrough of the cell membranes of the single cells can be realized. However, most of the existing micro-nano robots are driven by using chemical fuels or a single external physical field as energy input, depend on toxic and harmful fuels, have short service life, weak driving capability, single control means and limited extensible functions, and are difficult to meet the puncture requirement for a single cell membrane. Therefore, how to provide a single cell puncturing method based on a micro-nano robot, overcoming the limitation of the existing micro-nano robot in the aspect of single cell puncturing, and meanwhile, aiming at the characteristic parameters of the micro-nano robot, building a driving control system of the micro-nano robot is a key problem which needs to be solved urgently.
Disclosure of Invention
The invention aims to provide a hammer-type micro-nano robot-based single cell puncture system, which can realize effective puncture breakthrough of a single cell membrane.
The purpose of the invention is realized by the following technical scheme:
a single cell puncture system based on a hammer type micro-nano robot comprises the hammer type micro-nano robot, a magnetic field generating device for driving the hammer type micro-nano robot to rotate and an ultrasonic field generating device for driving the hammer type micro-nano robot to move;
the hammer type micro-nano robot comprises a hammer head and a hammer handle, and the hammer head has paramagnetism;
the hammer head is made of ferric oxide, and the hammer handle is made of silicon dioxide;
the hammer type micro-nano robot is prepared by a sol-gel process and a chemical precipitation process;
the hammer type micro-nano robot has an asymmetric structure;
the magnetic field generating device is a three-dimensional Helmholtz coil;
a signal generator is used for generating sine wave signals, the sine wave signals are amplified by a power amplifier and then are input into a Helmholtz coil as a signal source, the Helmholtz coil provides a rotating magnetic field, and the hammer type micro-nano robot is driven to show autorotation movement behavior;
the ultrasonic field generating device is an interdigital transducer taking lithium niobate as a substrate, and a signal generator is utilized to generate a high-frequency sine wave signal which is used as a signal source and input into the interdigital transducer;
the interdigital transducer converts an input high-frequency sine wave signal into mechanical vibration and transmits the mechanical vibration along the substrate in a planar ultrasonic mode, and the hammer type micro-nano robot shows a horizontal movement behavior under the action of a planar ultrasonic field provided by the interdigital transducer;
processing a polydimethylsiloxane micro-channel by adopting a micro-channel processing technology, bonding the polydimethylsiloxane micro-channel with a lithium niobate substrate, and providing a fluid environment for cell puncture of the hammer type micro-nano robot;
the beneficial effects of the invention are as follows:
the hammer handle of the hammer type micro-nano robot prepared by the sol-gel and chemical precipitation process is thin, so that the micro-nano robot can obtain higher puncture force in the process of breaking cell membranes;
the hammer-type micro-nano robot can respond to an external magnetic field and an ultrasonic field at the same time, the motion state of the hammer-type micro-nano robot can be controlled by adjusting parameters of the magnetic field and the ultrasonic field, and the remote and controllable cell puncture function can be realized;
the micro-nano robot is driven by magnetic field and ultrasonic field coupling, so that the micro-nano robot has higher driving capability and larger thrust-weight ratio, and the micro-nano robot is easier to break through cell membrane barriers of single cells;
the hammer-type micro-nano robot is used for cell puncture, so that the existing artificial cell puncture means can be replaced, the cell puncture precision and efficiency are improved, and manpower and material resources are greatly saved.
Drawings
The invention is described in further detail below with reference to the accompanying drawings and specific embodiments.
FIGS. 1 to 4 are a scanning electron microscope image and an energy spectrum image of the hammer type micro-nano robot;
FIG. 5 is a schematic diagram of a driving control system of the hammer type micro-nano robot;
FIG. 6 is a schematic diagram of a driving mechanism of the hammer type micro-nano robot;
fig. 7 to 10 are experimental diagrams of motion control of the hammer type micro-nano robot according to the invention;
fig. 11 to 13 are cell puncture experimental diagrams of the hammer type micro-nano robot of the invention.
Detailed Description
The present invention will be described in further detail with reference to the accompanying drawings.
A single cell puncture system based on a hammer type micro-nano robot comprises the hammer type micro-nano robot, a magnetic field generating device for driving the hammer type micro-nano robot to rotate and an ultrasonic field generating device for driving the hammer type micro-nano robot to move are further arranged; the hammer type micro-nano robot comprises a hammer head and a hammer handle, wherein the hammer head has paramagnetism;
scanning electron microscope images and energy spectrum images of the hammer type micro-nano robot are shown in fig. 1 to 4, the hammer head is made of ferric oxide, the hammer handle is made of silicon dioxide, and the fact that the hammer head of the micro-nano robot is made of ferric oxide and the hammer handle is made of silicon dioxide is proved;
because the hammer head material of the hammer type micro-nano robot is ferric oxide and has paramagnetism, the long axis of the hammer head of the micro-nano robot, namely the X axis, is always parallel to the direction of an external magnetic field under the action of the external magnetic field. Therefore, when the applied magnetic field is a plane rotating magnetic field, the micro-nano robot can show autorotation movement behavior under the driving of the hammer head;
meanwhile, the hammer type micro-nano robot has an asymmetric structure, so that a horizontal motion behavior can be shown in a low sound pressure gradient direction in a mode that a hammer handle faces forwards under the action of a horizontal ultrasonic field;
the hammer type micro-nano robot is prepared by a sol-gel process and a chemical precipitation process, and the hammer handle of the hammer type micro-nano robot prepared by the sol-gel process and the chemical precipitation process is thinner, so that the micro-nano robot can obtain higher puncture force in the process of breaking through cell membranes;
as shown in fig. 5 to 13, the structure and function of the magnetic field generating device and the ultrasonic field generating device will be described in detail;
as shown in fig. 5, observation was performed using an inverted microscope. The three-dimensional Helmholtz coil is used as a magnetic field generating device of a driving control system, a signal generator is used for generating sine wave signals, the sine wave signals are amplified by a power amplifier and then input into the Helmholtz coil as a signal source to generate a three-way uniform strong magnetic field, and two directions in the three-way uniform strong magnetic field are combined to form a plane uniform rotating magnetic field (20Hz, 3.71mT). The hammer type micro-nano robot rotates around a long axis, namely a Z axis, and shows a self-rotation motion behavior under the action of a rotating magnetic field.
The interdigital transducer is used as an ultrasonic field generating device of a driving control system, is prepared by sequentially depositing 7 nm chromium, 200 nm aluminum and 300 nm silicon dioxide on a Y-128-degree lithium niobate substrate, and generates a high-frequency sine wave signal (100kHz, 10Vpp) by using a signal generator to serve as a signal source to be input into the interdigital transducer. According to the inverse piezoelectric effect, the interdigital transducer converts an input high-frequency electric signal into mechanical vibration and transmits the mechanical vibration along the lithium niobate substrate in the form of planar ultrasonic waves. The hammer type micro-nano robot shows horizontal movement behavior under the action of plane ultrasonic waves generated by the interdigital transducer. And a micro-channel processing technology is adopted to process the polydimethylsiloxane micro-channel and is bonded with the lithium niobate substrate, so that a fluid environment is provided for the cell puncture of the hammer-type micro-nano robot.
After a driving control system of the hammer type micro-nano robot is started, an ultrasonic field generating device generates plane ultrasonic waves to push the hammer type micro-nano robot to move horizontally; the magnetic field generating device generates a plane uniform rotating magnetic field to push the hammer type micro-nano robot to rotate around a long axis of the hammer type micro-nano robot, namely a Z axis; under the coupling effect of two physical fields, the hammer type micro-nano robot can perform high-frequency autorotation while performing horizontal rapid motion, and drill into a target cell to realize the function of puncturing a single cell, as shown in fig. 6.
By using the driving control system provided by the invention, the movement behavior of the hammer type micro-nano robot can be regulated and controlled by changing the characteristic parameters of the externally applied physical field. The control of the motion speed of the hammer type micro-nano robot can be realized by changing the ultrasonic amplitude of the ultrasonic field. The ultrasonic frequency of the ultrasonic field is changed, the control of the motion direction of the hammer type micro-nano robot can be realized, as shown in fig. 7 to 10, the hammer type micro-nano robot and the chicken red blood cells are simultaneously injected into a micro channel, the external physical field parameters are changed, the motion speed and the motion direction of the hammer type micro-nano robot are controlled, and the function of puncturing a single cell can be effectively realized, as shown in fig. 11 to 13.

Claims (10)

1. A unicellular puncture system based on hammer type micro-nano robot comprises a hammer type micro-nano robot and is characterized in that: the ultrasonic vibration generator is also provided with a magnetic field generating device for driving the hammer type micro-nano robot to rotate and an ultrasonic field generating device for driving the hammer type micro-nano robot to move.
2. The hammer-type micro-nano robot-based single cell puncture system according to claim 1, characterized in that: the hammer type micro-nano robot comprises a hammer head and a hammer handle, wherein the hammer head has paramagnetism.
3. The hammer-type micro-nano robot-based single cell puncture system according to claim 2, characterized in that: the hammer head is made of ferric oxide, and the hammer handle is made of silicon dioxide.
4. The hammer-type micro-nano robot-based single cell puncture system according to any one of claims 1 to 3, characterized in that: the hammer type micro-nano robot is prepared by a sol-gel process and a chemical precipitation process.
5. The hammer-type micro-nano robot-based single cell puncture system according to any one of claims 1 to 3, characterized in that: the hammer type micro-nano robot has an asymmetric structure.
6. The hammer-type micro-nano robot-based single cell puncture system according to claim 1, characterized in that: the magnetic field generating device is a three-dimensional Helmholtz coil.
7. The hammer-type micro-nano robot-based single cell puncture system according to claim 6, wherein: a signal generator is used for generating sine wave signals, the signals are amplified by a power amplifier and then input into a Helmholtz coil as a signal source, the Helmholtz coil provides a rotating magnetic field, and the hammer type micro-nano robot is driven to show autorotation movement behaviors.
8. The hammer-type micro-nano robot-based single cell puncture system according to claim 1, characterized in that: the ultrasonic field generating device is an interdigital transducer taking lithium niobate as a substrate, and a signal generator is utilized to generate a high-frequency sine wave signal which is used as a signal source to be input into the interdigital transducer.
9. The hammer-type micro-nano robot-based single cell puncture system according to claim 8, characterized in that: the interdigital transducer converts an input high-frequency sine wave signal into mechanical vibration and transmits the mechanical vibration along the substrate in a planar ultrasonic mode, and the hammer type micro-nano robot shows horizontal movement behavior under the action of a planar ultrasonic field provided by the interdigital transducer.
10. The hammer-type micro-nano robot-based single cell puncture system according to claim 9, characterized in that: the polydimethylsiloxane micro-channel is processed by adopting a micro-channel processing technology and is bonded with a lithium niobate substrate, so that a fluid environment is provided for cell puncture of the hammer type micro-nano robot.
CN202210974703.9A 2022-08-15 2022-08-15 Single-cell puncture system based on hammer type micro-nano robot Active CN115386487B (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR200243812Y1 (en) * 2001-04-28 2001-10-12 안재목 Low frequency magnetic field exposure device
KR20140026958A (en) * 2012-08-24 2014-03-06 전남대학교산학협력단 Micro-robot system
WO2017101149A1 (en) * 2015-12-18 2017-06-22 中国科学院深圳先进技术研究院 Vertical mobile puncture robot
CN111592048A (en) * 2020-06-03 2020-08-28 四川轻化工大学 Spindle-shaped iron oxide nano material and preparation method and application thereof
CN113288421A (en) * 2021-05-07 2021-08-24 山东商业职业技术学院 Minimally invasive breast interventional operation robot and operation method thereof
CN114601509A (en) * 2020-12-08 2022-06-10 长春工业大学 Design of magnetic drive micro-nano robot, preparation method and drive mode thereof

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Publication number Priority date Publication date Assignee Title
KR200243812Y1 (en) * 2001-04-28 2001-10-12 안재목 Low frequency magnetic field exposure device
KR20140026958A (en) * 2012-08-24 2014-03-06 전남대학교산학협력단 Micro-robot system
WO2017101149A1 (en) * 2015-12-18 2017-06-22 中国科学院深圳先进技术研究院 Vertical mobile puncture robot
CN111592048A (en) * 2020-06-03 2020-08-28 四川轻化工大学 Spindle-shaped iron oxide nano material and preparation method and application thereof
CN114601509A (en) * 2020-12-08 2022-06-10 长春工业大学 Design of magnetic drive micro-nano robot, preparation method and drive mode thereof
CN113288421A (en) * 2021-05-07 2021-08-24 山东商业职业技术学院 Minimally invasive breast interventional operation robot and operation method thereof

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