CN104232614B - Cell magnetic force micromanipulation method and system under physiological environment - Google Patents

Cell magnetic force micromanipulation method and system under physiological environment Download PDF

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CN104232614B
CN104232614B CN201310254647.2A CN201310254647A CN104232614B CN 104232614 B CN104232614 B CN 104232614B CN 201310254647 A CN201310254647 A CN 201310254647A CN 104232614 B CN104232614 B CN 104232614B
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magnetic
cell
probe
magnetic force
nano
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CN104232614A (en
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曲英敏
王作斌
刘劲芸
侯煜
刘洋
王国梁
李文君
翁占坤
李景梅
宋正勋
胡贞
许红梅
于淼
刘兰娇
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Changchun University of Science and Technology
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Changchun University of Science and Technology
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Abstract

The invention discloses cell magnetic force micromanipulation method and system under a kind of physiological environment.The system of cell magnetic force micromanipulation is in the culture environment for the suitable cell in-vitro growth that the system being made up of magnetic probe, probe nano offset detection module, three-D displacement platform, inverted/upright light microscope, magnetic probe control module and Bit andits control module is placed in accurate control under physiological environment, realizes the external operation of biological cell and real-time tracking observation.The method of cell magnetic force micromanipulation is to be based on being combined cell magnetic force micromanipulation with magnetic nano-particle, by selection region point-to-point measurement and magnetic force size is recorded to the individual cells containing magnetic nano-particle using magnetic probe, magnetic force and pattern dot matrix image are obtained in nanoscale simultaneously, it is accurately positioned magnetic cell and magnetic nano-particle, and then individual cells are operated, moved, carried, inject and tested with magnetic probe, this has directive significance to nanometer biotechnology and micro-nano manipulation technology.

Description

Cell magnetic force micromanipulation method and system under physiological environment
Technical field
The present invention relates to the cell magnetic force micromanipulation method and system under physiological environment, its potential application includes following section Skill field:Bioscience, medical science, electronics, computer science etc..
Technical background
Nanoscale magnetic measurement is one of very important nanometer technology, and its application prospect is extremely wide, especially exists The research of biomedical sector is significant.
Nineteen ninety, IBM Eigler etc. under the conditions of high vacuum and extremely low temperature, using PSTM 35 Xenon atom has been combined into " IBM " printed words in nickel surface, so as to realize the resettlement of atom first.Stark in 1998 etc. utilizes atom Force microscope probe has carried out imaging and rupturing operation experiment to DNA.Kim in 2012 etc. has found that cancer is thin using AFM The property of born of the same parents' apoptosis is relevant with surface topography roughness and rigid change, and the change of pattern and biological nature can assess anticancer The activity of medicine.
Some domestic scientific research institutions have carried out micro-manipulating robot system and its research work in terms of biotechnology.North Biological cell micro OS of the robot Research Institute of navigating based on optical microscopy, has carried out the base of mouse egg cell Because injection is studied;Robot of Nankai University have developed the micro-manipulating robot towards bioengineering based on optical microphotograph vision System, and carried out the cutting test of chromosome of wheat;Precision instrument National Key Laboratory of Tsing-Hua University also constructs laser Microbeam operating operation test system, the optical tweezer capture for realizing particulate by accurate control trap platform position is cut with finishing tool, and is by this System realizes the experiments such as spore operation, chromosome cutting.
Because cell there is no magnetic, and biological cell manipulate under physiological environment and certain hardly possible be present Degree, so the magnetic research that micro-nano manipulation technology is applied to cell in vitro has not yet to see relevant report.Based on Cell magnetic Power micromanipulation system is combined with magnetic nano-particle, and the individual cells containing magnetic nano-particle are pressed using magnetic probe Selection region point-to-point measurement simultaneously records magnetic force size, obtains magnetic force and pattern dot matrix image simultaneously in nanoscale, is accurately positioned Magnetic cell and magnetic nano-particle, and then individual cells are operated, moved, carried, inject and tested with magnetic probe. Cell magnetic force micromanipulation method and system is provided directly in cell, subcellular fraction for life science under physiological environment Or the technology and instrument of Molecular level study biological phenomena, can be provided for the diagnosis and treatment of cancer cell science it is theoretical according to According to.
The content of the invention
It is an object of the invention to provide cell magnetic force micromanipulation method and system under physiological environment, by living to biology Body cell is detected, manipulated to realize active somatic cell configuration, physical characteristic, dynamic process, surface in real time in growing environment The acquisition of the information such as the distribution of acceptor and active state, field of biomedical research is provided directly in cell, subcellular fraction And the technology and instrument of Molecular level study biological phenomena.
The present invention implementation method be:, will be by magnetic probe, probe nano offset detection module, three under physiological environment The system that dimension displacement platform, inverted/upright light microscope, magnetic probe control module and Bit andits control module form is placed in essence In the culture environment of the suitable cell in-vitro growth of close control, using magnetic probe to the individual cells containing magnetic nano-particle By selection region point-to-point measurement and magnetic force size is recorded, magnetic force and pattern dot matrix image are obtained simultaneously in nanoscale, it is accurate fixed Position magnetic cell and magnetic nano-particle, and then individual cells are operated, moved, carried, inject and surveyed with magnetic probe Examination.
The invention has the advantages that:
Magnetic force microscopy is combined with inverted/upright light microscope can be accurately positioned magnetic cell and magnetic nano particle Son, improve scan efficiency and scanning precision.The combination of system and cell injuring model environment to cell magnetic force micromanipulation Use, the operation to external living cells can be achieved, obtain magnetic force and pattern dot matrix image simultaneously in nanoscale, magnetic can be used Probe is operated to individual cells, is moved, is carried, injected and tested.
Embodiment
As shown in figure 1, to cell magnetic force micromanipulation system include by magnetic probe, probe nano offset detection module, Three-D displacement platform, inverted/upright light microscope, magnetic probe control module, Bit andits control module and environmental control system Composition.Liquid cell is placed on above scanner, and the cover glass with cell is placed in pond, and piezoelectric ceramic tube is alive outside Under effect, liquid cell self-movement in the x, y, and z directions can be controlled.The laser beam that diode laser is sent passes through optics System focuses on the micro-cantilever back side, then through in micro-cantilever backside reflection to photodetector.Due to sample surfaces atom with it is micro- The interatomic interaction force of cantilevered probe needles, in Sample Scan, micro-cantilever will be bent with sample surface morphology Rise and fall, the reflected beams will also be offset therewith, and then change of the can by detecting facula position obtains the surface of sample Topographical information, meanwhile, the individual cells containing magnetic nano-particle by selection region point-to-point measurement and are remembered using magnetic probe Magnetic force size is recorded, magnetic force and pattern dot matrix image is obtained simultaneously in nanoscale, is accurately positioned magnetic cell and magnetic nano particle Son, and then individual cells are operated, moved, carried, inject and tested with magnetic probe.

Claims (1)

1. a kind of cell magnetic force micromanipulation method under physiological environment, it is characterised in that:It will be offset by magnetic probe, probe nano Detection module, three-D displacement platform, inverted/upright light microscope, magnetic probe control module and Bit andits control module composition The system suitable cell in-vitro growth that is placed in accurate control culture environment in, using magnetic probe to containing magnetic nano particle The individual cells of son by selection region point-to-point measurement and record magnetic force size, and magnetic force and pattern dot matrix are obtained simultaneously in nanoscale Image, magnetic cell and magnetic nano-particle are accurately positioned, and then individual cells are operated with magnetic probe, including moved Dynamic, injection and test;
By the magnetic force of probe or additional electromagnetic force with being interacted with magnetic nano particle daughter cell, detection magnetic force size is with weight The Distribution of Magnetic Field of structure measured zone;
Under physiological environment, cell fast rough is carried out using inverted/upright light microscope, selects magnetic imaging, operation Target location;
The preparation method of the cell with magnetic nano-particle:It is one or more using the absorption of magnetic probe needle point, control Magnetic nano-particle is simultaneously implanted into selected cell, obtains the cell that ad-hoc location carries magnetic nano-particle, carry out magnetic force it is micro- into Picture and manipulation;Or co-culture cell and magnetic nano-particle, obtained by encytosis containing one or more magnetic The cell of nano-particle distribution, carries out magnetic force micro-imaging and operation;Probe contact is selected to be connect with non-by probe control module Tactile mode carries out micrometering and operation;
To the system of cell magnetic force micromanipulation and being used in combination for cell injuring model environment in the system, can be achieved to external The operation of living cells, magnetic force and pattern dot matrix image are obtained simultaneously in nanoscale.
CN201310254647.2A 2013-06-15 2013-06-15 Cell magnetic force micromanipulation method and system under physiological environment Active CN104232614B (en)

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CN106148185B (en) * 2015-04-13 2018-11-27 浙江大学 Real-time electromagnetic field cell exposure system and its application
CN105607686B (en) * 2016-01-11 2017-02-01 浙江大学 Nanometer-level-microoperation-based unicellular sub-nanometer-level motion control system
CN106501554B (en) * 2016-11-16 2019-01-29 长春理工大学 A kind of method of operating for moving magnetic nano-particle
CN106841684B (en) * 2017-01-16 2019-05-21 长春理工大学 The cooperated measuring method of cell growth state
CN110018332B (en) * 2019-04-30 2021-08-06 长春理工大学 Atomic force probe contact type scanning biological cell imaging error compensation method
CN112285386A (en) * 2020-10-13 2021-01-29 长春理工大学 Detection method of tumor exosome induced cell malignant change process based on atomic force microscopy

Citations (2)

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WO2010036957A1 (en) * 2008-09-25 2010-04-01 William Marsh Rice University Systems and methods for magnetic guidance and patterning of cells and materials
WO2011038370A1 (en) * 2009-09-25 2011-03-31 N3D Biosciences, Inc. Materials for magnetizing cells and magnetic manipulation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010036957A1 (en) * 2008-09-25 2010-04-01 William Marsh Rice University Systems and methods for magnetic guidance and patterning of cells and materials
WO2011038370A1 (en) * 2009-09-25 2011-03-31 N3D Biosciences, Inc. Materials for magnetizing cells and magnetic manipulation

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