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WO2017008699A1 - Dispositif de mesure de la force de traction de cellule, et procédé de mesure et procédé de préparation - Google Patents

Dispositif de mesure de la force de traction de cellule, et procédé de mesure et procédé de préparation Download PDF

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Publication number
WO2017008699A1
WO2017008699A1 PCT/CN2016/089401 CN2016089401W WO2017008699A1 WO 2017008699 A1 WO2017008699 A1 WO 2017008699A1 CN 2016089401 W CN2016089401 W CN 2016089401W WO 2017008699 A1 WO2017008699 A1 WO 2017008699A1
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WIPO (PCT)
Prior art keywords
nanowire
cell
layer
measuring device
traction
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Ceased
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PCT/CN2016/089401
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English (en)
Chinese (zh)
Inventor
李舟
金一鸣
张亚岚
郑强
欧阳涵
王中林
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Beijing Institute of Nanoenergy and Nanosystems
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Beijing Institute of Nanoenergy and Nanosystems
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Publication of WO2017008699A1 publication Critical patent/WO2017008699A1/fr
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y40/00Manufacture or treatment of nanostructures
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence

Definitions

  • the present invention relates to the technical field of cell measurement, and in particular to a cell traction measuring device, a measuring method and a preparation method.
  • Traction is one of the most important properties of cells. It is associated with many complex biological signal-mediated channels and plays an important role in cell proliferation, differentiation, contraction, migration and apoptosis. In addition, cell traction is highly correlated with the development and progression of many diseases, such as tumors. Therefore, some quantitative studies of individual cells are of great interest in both physiology and pathology.
  • cell traction is typically measured based on a soft nano/micro line array.
  • cell traction is calculated by measuring the amount of bending of the microcolumn based on a PDMS (polydimethylsiloxane) microcolumn array.
  • PDMS polydimethylsiloxane
  • this method has great limitations: (1) the measurement method is limited, and it is necessary to fix the cells and perform SEM (scanning electron microscope) observation, which cannot reflect the traction of living cells in real time; (2) soft A nanowire array (such as a PDMS microcolumn array) not only bends but also elastically deforms (axially stretches) when subjected to force, thereby affecting the accuracy of cell traction measurement; (3) nano-line shape according to SEM photographs It is subject to mechanical quantification, more interference by human factors, and greater error; (4) SEM price is more expensive, which is not conducive to popularization.
  • SEM scanning electron microscope
  • the present invention provides a cell traction measuring device, the measuring device comprising: a base layer; a nanowire layer on the base layer, comprising a nanowire array, the nanowires in the array being used for And being capable of being bent by an external force; and an illuminating layer comprising a light-emitting point disposed at an end of each of the nanowires for supporting the cell to be tested after the cell to be tested is placed on the luminescent layer
  • the nanowire is bent to drive the light-emitting point of the end of the nanowire to move, resulting in an offset displacement that characterizes the traction of the cell.
  • the measuring device for cell traction of the present invention can directly place the cell to be tested on the light emitting layer by providing a light emitting layer on the nanowire layer, and obtain the table in real time according to the movement of the light emitting point in the light emitting layer.
  • the displacement displacement of the cell traction force is high and the accuracy is high.
  • Another object of the present invention is to provide a method for preparing a cell traction measuring device, the method comprising: providing a substrate layer; generating a nanowire layer on the substrate layer, the nanowire layer comprising a nanowire array The luminescent material is modified at the ends of the nanowires within the array to form a luminescent layer.
  • the preparation method of the cell traction measuring device of the invention can obtain the cell traction force measuring device by sequentially forming the nanowire layer and the luminescent layer on the substrate layer, and the preparation method is simple and convenient to operate.
  • FIG. 1 is a schematic structural view of a measuring device for cell traction of the present invention
  • FIG. 2 is a front view showing a dynamic view of a cell traction measuring device of the present invention
  • Fig. 3 is a top plan view showing the apparatus for measuring the cell traction force of the present invention.
  • the measuring device for cell traction of the present invention comprises a base layer 3; a nanowire layer 1 on the base layer 3, comprising a nanowire array, the nanowires in the array being used for receiving an external force When functional, capable of bending; and the luminescent layer 2, including each of the nanowires 11
  • the light-emitting point 21 at the end of the nanowire 11 is used to move the light-emitting point 21 at the end of the nanowire 11 after the cell 4 to be tested is placed on the light-emitting layer 2 , producing an offset displacement that characterizes the cell's traction.
  • the measuring device for cell traction of the present invention can directly place the cell to be tested on the luminescent layer by disposing a luminescent layer on the nanowire layer, and obtain an offset displacement characterization of the cell traction force in real time according to the movement of the illuminating point in the luminescent layer.
  • the accuracy is high; and in the measurement process, the cells can be detected without the need to fix the cells.
  • the nanowire 11 of the cell traction measuring device of the present invention is made of a hard material having a Young's modulus.
  • the hard material may be a metal, a non-metal or a compound thereof, for example, the metal may be germanium (Ge), lead (Pb), copper (Cu), silver (Ag) or platinum (Pt), etc.
  • the non-metal may be silicon (Si) or selenium (Se), and the compound may be gallium nitride (GaN), silicon dioxide (SiO 2 ), zinc oxide (ZnO) or zinc sulfide (ZnS), etc. Not limited to this.
  • the entire measuring device can be made transparent, and the nanowire 11 is made of a transparent material.
  • the nanowire 11 is made of a transparent material.
  • glass or quartz can be selected.
  • the density of the nanowires 11 in the nanowire layer 1 is 1 ⁇ 10 5 /cm 2 -1 ⁇ 10 8 /cm 2 .
  • the nanowire 11 has an aspect ratio of 5-50; in general, the nanowire 11 has a length of 1-20 ⁇ m and a diameter of 50-500 nm.
  • the light-emitting point 21 in the light-emitting layer 2 is made of a light-emitting material.
  • the luminescent material can be a quantum dot and/or a fluorescent dye.
  • the quantum dots may be cadmium sulfide (CdS), cadmium selenide (CdSe), cadmium telluride (CdTe), zinc sulfide (ZnS), etc.
  • the fluorescent dye may be fluorescein isothiocyanate , FITC), tetraethyl rhodamine B200 (RB200), tetraethyl rhodamine isothiocyanate (TRITC), phycoerythrin (R-Re), 4,6 - 4,6-diamidino-2-phenylindole (DAPI), etc., at a lower cost.
  • the invention also provides a method for measuring cellular traction.
  • the measuring method of the cell traction force comprises: placing the cell to be tested on the luminescent layer in the measuring device for the cell traction force; and obtaining an offset displacement characterization of the cell traction force according to the movement of the illuminating point in the illuminating layer; The traction of the cells to be tested is determined.
  • external stimuli such as light, electricity, force or biochemical molecules, can also be applied to the cells to speed up the spreading of the cells and shorten the measurement time.
  • the invention does not need to use a more expensive SEM when measuring the cell traction force, and only needs to use an ordinary optical microscope (for example, a metallographic microscope or an inverted fluorescence microscope). Convenient and fast, low cost and wide range of use.
  • the present invention provides a method of preparing a cell traction measuring device.
  • the preparation method includes: providing a base layer; generating a nanowire layer on the base layer, the nanowire layer comprising a nanowire array; modifying a luminescent material at an end of the nanowire in the array to form a luminescent layer .
  • the method for generating a nanowire layer on the base layer includes: when the base layer and the nanowire layer are the same material, generally etching a nanowire layer on the substrate by etching; When the base layer and the nanowire layer are of different materials, a nanowire layer is grown and/or deposited on the base layer by techniques such as hydrothermal and/or epitaxial growth.
  • the etching method includes: at least one of Metal-Assisted Chemical Etching (MACE), Electron Beam Lithography (EBL), and Laser Interference Lithography (LIL).
  • MACE Metal-Assisted Chemical Etching
  • EBL Electron Beam Lithography
  • LIL Laser Interference Lithography
  • a method of modifying a luminescent material at an end of a nanowire within the array includes: affixing a luminescent material to an end of the nanowire by a nano-seal technique; or coating a hydrophilic layer on the nanowire layer Etching the hydrophilic substance with a plasma or the like to expose an end of the nanowire; adding a luminescent material (the luminescent material is a hydrophobic substance), and modifying an end of the nanowire with the a luminescent material; the hydrophilic substance is dissolved using a solvent.
  • the plasma may be an Inductively Coupled Plasma (ICP) or a Reactive Ion Etching (RIE), but is not limited thereto.
  • the method for preparing a cell traction measuring device of the present invention can obtain a cell traction force measuring device by sequentially forming a nanowire layer and a light emitting layer on a substrate layer, the preparation method is simple, the operation is convenient; and the prepared cell traction force measuring device structure Simple, high measurement accuracy and wide range of use.

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Nanotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • Manufacturing & Machinery (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Force Measurement Appropriate To Specific Purposes (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Abstract

L'invention concerne un dispositif de mesure de la force de traction de cellule, et un procédé de mesure et un procédé de préparation, le dispositif de mesure comprenant : une couche de substrat (3) ; une couche de nanofils (1) située sur la couche de substrat (3), comprenant des réseaux de nanofils, des nanofils (11) pouvant être courbés sous l'effet d'une force externe ; et une couche électroluminescente (2), comprenant des points lumineux (21) agencés sur l'extrémité de chaque nanofil (11), et supportant la courbure des nanofils (11) d'une cellule de support (4) à analyser, et entraînant le mouvement du point lumineux (21) sur l'extrémité du nanofil (11) pour produire le déplacement de décalage représentant la force de traction de la cellule (4) après que la cellule (4) à analyser est agencée sur la couche électroluminescente (2). Le dispositif de mesure de la force de traction de cellule acquiert le déplacement de décalage représentant la force de traction de la cellule (4) en temps réel en fonction de la situation de mouvement du point lumineux (21) de la couche électroluminescente (2), et présente une grande précision.
PCT/CN2016/089401 2015-07-10 2016-07-08 Dispositif de mesure de la force de traction de cellule, et procédé de mesure et procédé de préparation Ceased WO2017008699A1 (fr)

Applications Claiming Priority (2)

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CN201510406035.X 2015-07-10
CN201510406035.XA CN106338500B (zh) 2015-07-10 2015-07-10 细胞牵引力的测量装置、测量方法及制备方法

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Cited By (1)

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FR3136480A1 (fr) 2022-06-13 2023-12-15 4Dcell Dispositif de culture cellulaire

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CN107238661B (zh) * 2017-05-31 2018-04-17 湖南农业大学 一种细胞牵引力与粘弹性的同时定量测定方法
CN108711591B (zh) 2018-05-22 2019-10-01 京东方科技集团股份有限公司 一种显示器件及其制备方法、显示装置
CN109827928B (zh) * 2019-02-02 2019-10-11 东南大学 多模态生物力学显微镜及测量方法
CN115876759A (zh) * 2021-09-26 2023-03-31 瑞新(福州)科技有限公司 细胞机械力的检测系统、方法、装置及其制备方法
AU2024247326A1 (en) * 2023-03-24 2025-11-13 Yigong Ruishi (Fujian) Engineering Research Center Co., Ltd. Multi-modal fluid characterization and disturbance system and method, and application

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Publication number Priority date Publication date Assignee Title
FR3136480A1 (fr) 2022-06-13 2023-12-15 4Dcell Dispositif de culture cellulaire
WO2023242495A1 (fr) 2022-06-13 2023-12-21 4Dcell Dispositif de culture cellulaire

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CN106338500B (zh) 2019-11-01

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