CN107045075B - A kind of characterizing method of the cell physical state based on porous media model - Google Patents

A kind of characterizing method of the cell physical state based on porous media model Download PDF

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CN107045075B
CN107045075B CN201710208656.6A CN201710208656A CN107045075B CN 107045075 B CN107045075 B CN 107045075B CN 201710208656 A CN201710208656 A CN 201710208656A CN 107045075 B CN107045075 B CN 107045075B
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CN107045075A (en
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任克礼
韩东
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National Center for Nanosccience and Technology China
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01QSCANNING-PROBE TECHNIQUES OR APPARATUS; APPLICATIONS OF SCANNING-PROBE TECHNIQUES, e.g. SCANNING PROBE MICROSCOPY [SPM]
    • G01Q60/00Particular types of SPM [Scanning Probe Microscopy] or microscopes; Essential components thereof
    • G01Q60/24AFM [Atomic Force Microscopy] or apparatus therefor, e.g. AFM probes

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Abstract

The present invention provides a kind of characterizing method of cell physical state based on porous media model.Above-mentioned characterizing method in order to obtain, it needs to obtain Young's Moduli based on porous media model first, wherein, the acquisition methods of Young's Moduli include: load force-time curve of the S1. based on cell surface to be measured, obtain loading force and compression distance of the cell to be measured when the time is region infinity;S2. the loading force and compression distance based on cell to be measured when the time is region infinity, the Young's modulus of cell to be measured is calculated using Hertz model.Method provided by the invention can efficiently solve the problem big using the result difference measured under conventional method different compression distances according to present in Hertz model measurement Young's modulus and cell rigidity and different loading speeds, and reasonably explain that the reason of difference occurs in conventional method measurement, and the accurately mesoporous resilient nature of characterization cell and cell physical state.

Description

A kind of characterizing method of the cell physical state based on porous media model
Technical field
The present invention relates to cell characterization technical fields, more particularly, to a kind of cell object based on porous media model The characterizing method of reason state.
Background technique
The method of existing description cyto-mechanics state mainly has rigid using Young's modulus characterization cell based on Hertz model Degree, characterizes cell with apparent viscosity using relaxation modulus based on Theory of Viscoelasticity, and is based on porous medium theory To calculate cytoplasmic diffusion coefficient.
The method that Young's Moduli is calculated using Hertz model mainly carries out cell using atomic force microscope Indentation test acquires power-distance Curve of cell, is fitted for probe of different shapes using different formula.
For tapered probe, indentation test is carried out to cell using tapered probe, as shown in figure 1 shown in (a), is had:
For spherical probes, indentation test is carried out to cell using tapered probe, as shown in figure 1 shown in (b), is had:
Wherein, F is loading force, and E is Young's modulus, and v is Poisson's ratio,It is half angle of release of tapered probe, R is spherical probes Radius, δ is compression distance.
It is first to allow probe certain with certain speed indentation cell using the method that viscoelastic model calculates viscosity and rigidity Compression distance, be then allowed to settle the regular hour, force curve a relaxation can occur with time of repose.By will be loose The force curve in relaxation stage is fitted with following equation:
Wherein, ERIt is relaxation modulus, τσAnd τsIt is the Relaxation time constant of load and deformation respectively, apparent viscosity can root It is calculated according to following formula:
μ=ERσε)
The power that AFM probe applies cell can pass through:
F=S × Δ × k
To calculate, wherein S is the susceptibility of probe, and Δ is the variation of deflection value, and k is the force constant of probe.
It is also mainly carried out using the curve in relaxation stage using the method for porous media model measurement cellular invasion coefficient Fitting.Fit equation is as follows:
For tapered probe, have:
α=(2/ π) δ tan θ
For spherical probes, have:
Wherein, D is diffusion coefficient, and α is effective contact area.
The method of the physical state of traditional characterization cell whether has it from model hypothesis or in data acquisition Deficiency.On model hypothesis, cell is assumed to be a Homogeneous Elastic Solid by Hertz model, and viscoelastic model regards cell as It is complete viscoelastic body, cell is assumed to be a single porous media system by porous media model.And these are assumed not Meet the state of cell itself.In data acquisition, Hertz model always exists two problems, first is that surveying under different compression distances The value of the Young's modulus measured has larger difference, second is that the value measured under different loading speeds also has larger difference.This Outside, previous a variety of models, all only with one or two kinds of physical parameters based on this model as characterization cyto-mechanics The main standard of state, and cell interior, due to its complexity, its physical state is described by one or two kinds of parameters may be simultaneously It cannot meet the needs, and the state of its description also has certain one-sidedness, locating for description cell that can not be accurate or perfect Physiological status.
Summary of the invention
(1) technical problems to be solved
The technical problem to be solved by the present invention is to how reduce to obtain under different compression distances and different loading speeds The obtained difference between Young's modulus value.
(2) technical solution
To solve the above-mentioned problems, the present invention provides a kind of acquisition methods of Young's Moduli, comprising:
S1. based on the load force-time curve of cell surface to be measured, cell to be measured is obtained when the time is region infinity Loading force and compression distance;
S2. the loading force and compression distance based on cell to be measured when the time is region infinity, utilizes Hertz model meter Calculation obtains the Young's modulus of cell to be measured.
Preferably, S1 specifically:
Based on deformation-time graph of cell surface AFM probe to be measured, cell surface to be measured is obtained using viscoelastic model Load force-time curve, obtain cell to be measured the time be region infinity when loading force and compression distance.
Preferably, in the acquisition of the deformation-time graph, data collection steps include: withdraw of the needle section, stand section, is close Needle section and slack strand.
Preferably, the data collection steps specifically:
S11. according to the force curve of cell to be measured, estimation is obtained the position of probe Yu cell contact point to be measured, is estimated with described Location is set to contact point, and probe is lifted and is placed in the first height, is denoted as withdraw of the needle section, acquires the time value and AFM probe of withdraw of the needle section Deflection changing value;
S12. probe is stood in first height, is denoted as standing section, acquisition stands the time value and AFM probe of section Deflection changing value;
S13. it enables probe decline first distance with First Speed, to obtain the first compression distance in cell surface, is denoted as Nearly needle section, acquires the time value and AFM probe Deflection changing value of nearly needle section;
S14. it keeps probe constant in first compression distance, records the relaxation behavior of probe, be denoted as slack strand, acquire The time value and AFM probe Deflection changing value of slack strand.
Preferably, the data collection steps further include:
Using S11-S14 as a cycle, multiple periods are repeated.
Preferably, the First Speed is at least 10 μm/s.
According to an aspect of the present invention, a kind of characterizing method of cell physical state is additionally provided, comprising: use Young Modulus, apparent viscosity and diffusion coefficient comprehensive characterization cell physical state;Wherein, the Young's modulus is to use above-mentioned cell poplar The measurement method of family name's modulus obtains.
Preferably, the apparent viscosity is the song of slack strand described in the measurement method based on above-mentioned Young's Moduli Line is fitted acquisition using viscoelastic model.
Preferably, the diffusion coefficient is the song of slack strand described in the measurement method based on above-mentioned Young's Moduli Line is fitted acquisition using porous media model.
Preferably, the characterizing method further include: use comprehensive porosity combination Young's modulus, apparent viscosity and diffusion system Number synthesis characterizes cell physical state;Wherein, the comprehensive porosity is calculated using single bore diameter porous MEDIUM THEORY and is obtained.
According to an aspect of the present invention, a kind of mesoporous elastic or rigidity the acquisition methods of cell are additionally provided, comprising: make The acquisition methods of the Young's Moduli described in preceding claim obtain Young's Moduli, to characterize the mesoporous elasticity of cell Or rigidity.
Method proposed by the present invention can be efficiently solved using conventional method based on porous media model according to conspicuous Hereby different compression distances present in model measurement Young's modulus and cell rigidity are obtained from measurement under different loading speeds The big problem of result difference, and reasonably explain that the reason of difference occurs in conventional method measurement;Cell characterization proposed by the present invention It is insufficient with incomplete, root present in cell physical state that method solves the problems, such as that tradition is described using various physical models According to multilevel multiphase porous medium theory, the essence more profound for disclosing intracellular mechanical behavior, more comprehensively more comprehensive description The physical state of cell interior.It can be adapted for tissue based on tissue and multilevel multiphase porous media, method of the invention Or biomimetic material, be applied to clinical medicine, it would be possible to help scientific worker see clearly disease occur the reason of and it is right The diagnosing and treating of disease.
Detailed description of the invention
Fig. 1 is the schematic diagram that tapered probe (a), spherical probes (b) carry out indentation test to cell respectively in the prior art;
Fig. 2 is the overview flow chart according to the acquisition methods of Young's Moduli in embodiment of the present invention;
Fig. 3 is according to the curve that z is changed over time to distance in a cycle experiment in a preferred embodiment of the invention Scheme the curve graph (b) and Deflection time history plot of (a), Deflection with z to distance change;
Fig. 4 is to obtain according in a preferred embodiment of the invention using measured by conventional method and method of the invention The curve graph that 3T3 Young's Moduli value changes with compression distance;
Fig. 5 is to obtain according in a preferred embodiment of the invention using measured by conventional method and method of the invention The curve graph that DC Young's Moduli value changes with loading speed.
Specific embodiment
With reference to the accompanying drawings and examples, specific embodiments of the present invention will be described in further detail.Implement below Example is not intended to limit the scope of the invention for illustrating the present invention.
The acquisition methods of Young's Moduli provided by the invention, as shown in Figure 2, comprising:
S1. based on the load force-time curve of cell surface to be measured, cell to be measured is obtained when the time is region infinity Loading force and compression distance;
S2. the loading force and compression distance based on cell to be measured when the time is region infinity, utilizes Hertz model meter Calculation obtains the Young's modulus of cell to be measured.
The present invention is based on the Young's modulus that porous media model obtains cell, it is contemplated that utilizes traditional Hertz model method The effect for the intracellular liquid phase that measurement Young's modulus is not considered.In the method for traditional measurement Young's modulus, only will Cell processing is pure elastomer, is equivalent to us with porous Jie for the data of the compression distance and loading force that calculate Young's modulus Matter model calculate when relaxation curve in t=0 data.And if by cell carry out porous media model processing, due to liquid The presence of phase, in t=0, intracellular liquid is not redistributed also mutually, and the also non-complete stability of the integrality of cell gets off, Therefore, measured obtained Young's modulus is highly susceptible to the influence of compression distance and loading speed.And it is bent if choosing relaxation Value in line when t=∞, intracellular liquid have mutually redistributed completely, and the integrality of cell has reached one completely Stable state, at this point, can exclude to cause to do from the different behaviors of liquid phase under loading speed in different compression distances It disturbs, therefore with certain superiority and higher accuracy.
Based on when the loading force and compression distance under the time is region infinity ∞ using t are 0 in unorthodox method Loading force and compression distance, the Young's modulus value being calculated using Hertz model is more accurate, reduces in different indentations The difference between Young's modulus value acquired under depth and different loading speeds.
Wherein, compression distance refers to probe in the compression distance on the surface of cell to be measured.
Hertz model is Hertz model commonly used in the art, usually mainly using atomic force microscope probe to thin Born of the same parents carry out indentation test acquisition cell force-displacement curve and AFM probe deformation-time (also referred to as Deflection-t, or The Deflection- time) curve.
It can use different formula for probe of different shapes to be fitted, for tapered probe, be visited using taper Indentation test is carried out for cell, as shown in figure 1 shown in (a), is had:
For spherical probes, indentation test is carried out to cell using tapered probe, as shown in figure 1 shown in (b), is had:
Wherein, F is loading force, and E is Young's modulus, and v is Poisson's ratio,It is half angle of release of tapered probe, R is spherical probes Radius, δ is compression distance.
In embodiments of the present invention, obtained loading force and compression distance are substituted into above-mentioned model, so that it may Obtain the Young's modulus of cell.
In a preferred embodiment of the invention, used is spherical probes, and diameter is usually 10 μm.Art technology Personnel can according to actual needs and the known advantage and disadvantage of each probe select different type or various sizes of probe.
In a preferred embodiment of the invention, more accurate loading force and compression distance, S1 are specific in order to obtain Are as follows:
Based on deformation-time graph of cell surface AFM probe to be measured, cell surface to be measured is obtained using viscoelastic model Load force-time curve, obtain cell to be measured the time be region infinity when loading force and compression distance.
Wherein, when probe is along testee apparent motion, the reaction force of measured surface makes probe, and deformation occurs.It uses When AFM probe, the load for obtaining cell surface to be measured can be gone by deformation-time graph of cell surface AFM probe to be measured Force-time curve.
Wherein, according to deformation-time (Deflection-t) curve of AFM probe, in viscoelastic model, AFM probe The power applied to cell can pass through:
F=S × Δ × k
The curve of loading force-time (F-t) is calculated, wherein S is the susceptibility of probe, and Δ is deflection The variation of value, k are the force constants of probe.
In order to keep data more accurate and obtain other characterization values, in a preferred embodiment of the invention, in deformation In the acquisition of the change curve of Deflection- time t, as shown in figure 3, data collection steps include: withdraw of the needle section, stand section, Nearly needle section and slack strand.
In order to reduce data acquisition to the Young's modulus measured under different compression distances and different loading speeds It influences, in a preferred embodiment of the invention, following methods is preferably selected to acquire data:
S11. according to the force curve of cell to be measured, estimation is obtained the position of probe Yu cell contact point to be measured, is estimated with described Location is set to contact point, and probe is lifted and is placed in the first height, is denoted as withdraw of the needle section, acquires the time value and AFM probe of withdraw of the needle section Deflection changing value;
S12. probe is stood in the first height, is denoted as standing section, acquisition stands the time value and AFM probe of section Deflection changing value;
S13. it enables probe decline first distance with First Speed, to obtain the first compression distance in cell surface, is denoted as Nearly needle section, acquires the time value and AFM probe Deflection changing value of nearly needle section;
S14. it keeps probe constant in the first compression distance, records the relaxation behavior of probe, be denoted as slack strand, acquisition relaxation The time value and AFM probe Deflection changing value of section.
It is also possible to Z-direction distance value is acquired respectively in withdraw of the needle section, standing section, nearly needle section and slack strand, it is available It is bent with Z-direction distance change (Deflection-Z to distance) that Z-direction distance changes over time (Z-direction distance-t) curve and deformation Line, as shown in figure 3, whole experiment process can be showed under different presentations.
Wherein, in S11, a force curve is done on cell to be measured to estimate the position of contact point.With the estimation position For contact point, probe is lifted and is placed in the first height d0
It, can be according to deformation in order to more accurately obtain the position of contact point in a preferred embodiment of the invention With Z-direction distance change (Deflection-Z to distance) curve, the linearity range of curve and the separation of non-linear section are to estimate Position estimates position as contact point using this, probe is lifted and is placed in the first height d0
In S12, section is being stood, probe is being stood into a period of time in first height, which, which can according to need, sets It sets.Different cells are possible to identical to the response of probe, it is also possible to which different, standing is to make cell restore normal shape for a moment State, this time needs are adjusted according to specific experimental subjects and phenomenon.Usually several seconds.
In S13, in nearly needle section, First Speed can according to need setting, at least speed of 10 μm/s in the present invention For be described in detail the present invention.Wherein, the second height is d1, compression distance δ.
In the velocity interval value, the liquid in cell is not yet redistributed.
In S14, in slack strand, due to the redistribution of cell flow phase, probe can show a time dependence Relaxation, record the relaxation behavior of probe.
It, can be by the first height d according to experiment needs0With first distance d1It is set as same or different value, can be collected Experimental data of the cell under same compression distance or different compression distances.
When the first height and first distance value are set as identical, that is, probe is lifted the first height and then is declined again and the The one identical distance of height, while being restored to normal condition by standing Procedure Cell, then position after decline and before lifting Position be same position, i.e., the compression distance tested twice be also it is the same, cell can be collected in same indentation depth Experimental data under degree.
More accurate data in order to obtain, data collection steps further include: S11-S14 is set as a cycle, is repeated more A period.
Wherein, " multiple " in the present invention refer to 2 or 2 or more.
I.e. after the completion of the experiment in said one period, the experiment of next cycle can be and then carried out.
The present invention also provides a kind of acquisition methods of cell rigidity, comprising: uses the measurement of above-mentioned Young's Moduli Method obtains Young's Moduli, to obtain the rigidity of cell.
Wherein, the rigidity of cell and Young's Moduli correspond, and from the perspective of biology, are all used to indicate that The soft or hard degree of cell.
Since the Young's modulus is inwardly measuring in porous media model, the above method can be measured again Obtained Young's modulus is referred to as the mesoporous elasticity of cell.
That is, the present invention also provides a kind of characterizing methods of the mesoporous elasticity of cell, comprising: use above-mentioned Young's Moduli Acquisition methods obtain Young's Moduli to be measured, to characterize the mesoporous elasticity of cell.
The present invention also provides a kind of characterizing methods of cell physical state, comprising: using Young's modulus, apparent viscosity and Diffusion coefficient comprehensive characterization cell physical state;Wherein, Young's modulus is to be obtained using the measurement method of above-mentioned Young's Moduli ?.
In characterizing method of the invention, cell is considered as a multilevel multiphase porous media, it is false in traditional model If on, cell is assumed to be a Homogeneous Elastic Solid by Hertz model, and viscoelastic model regards cell as complete viscoelastic body, more Cell is assumed to be a single porous media system by hole dielectric model.And these hypothesis do not meet the shape of cell itself State.Cell is innovatively considered as a multilevel multiphase porous media, uses the present invention by the state based on cell itself, the present invention Measured obtained Young's modulus combination apparent viscosity and diffusion coefficient carry out comprehensive characterization cell physical state, wherein use this The Young's modulus that the method for invention obtains more can reflect the state of cytoskeleton, apparent viscosity then with the state relation of cell liquid Bigger, the diffusion coefficient comprehensive description active state of one cell interior compensates for previous various models and carries out object to cell Manage deficiency present in state representation.
For the state of more acurrate reflection cell liquid, apparent viscosity is the measurement side of Young's Moduli according to the present invention The curve of slack strand in method is fitted acquisition using viscoelastic model.
For the active state of more acurrate reflection cell interior, diffusion coefficient is Young's Moduli according to the present invention The curve of slack strand in measurement method is fitted acquisition using porous media model.
The curve of above-mentioned slack sections is the slack sections curve in deformation-time (Deflection-t) curve of cell, then Power-time (F-t) curve for obtaining the slack sections curve is calculated according to F=S × Δ × k, is utilized respectively viscoelastic model progress Fitting is obtained cell apparent viscosity value and is fitted the diffusion coefficient for obtaining cell using porous media model.
Entire deformation-time (Deflection-t) curve of cell can also be calculated according to F=S × Δ × k and be obtained Corresponding power-time (F-t) curve is utilized respectively viscoelastic model and is fitted acquisition further according to the curve of wherein slack strand Cell apparent viscosity value and the diffusion coefficient that acquisition cell is fitted using porous media model.
Wherein, being fitted using viscoelastic model and obtaining cell apparent viscosity value is method common in this field, In a preferred embodiment of the invention, specifically:
By the way that the F-t curve of slack sections is fitted with following equation:
Wherein, ERIt is relaxation modulus, τσAnd τsIt is the Relaxation time constant of load and deformation respectively, apparent viscosity can root It is calculated according to following formula:
μ=ERσε)
Wherein, being fitted using porous media model and obtaining the diffusion coefficient of cell is method common in this field, In a preferred embodiment of the invention, specifically:
By the way that the F-t curve of slack sections is fitted with following equation:
For the spherical probes in a preferred embodiment of the invention, have:
Wherein, D is diffusion coefficient, and α is effective contact area.
The available diffusion coefficient D value from above formula.
In porous media, in order to more comprehensively reflect the physical state of cell, usually also need using comprehensive hole Degree combines Young's modulus, apparent viscosity and diffusion coefficient to come together to characterize cell physical state.
In the present invention, comprehensive porosity can use single bore diameter porous MEDIUM THEORY and calculate acquisition, that is, Young mould Amount, apparent viscosity, diffusion coefficient and pore size have following relationship:
Wherein, ξ is pore size, characterizes comprehensive porosity;D is diffusion coefficient;α is effective contact area;E is Young mould Amount.
In one preferred embodiment, since the different most probables of intracellular porous media structure are embodied in its pattern In feature, therefore take the biggish two kinds of cell 3T3 cells of two kinds of varying topographies and DC cell as experimental subjects.Wherein, 3T3 Cell is big and thin, and DC cell is small and thick.
3T3 cell and DC cell are measured using method of the invention, as shown in figure 4, having obtained for 3T3 cell The Young's modulus value obtained under different compression distances using conventional method and method of the invention, as shown in figure 5, having obtained needle The Young's modulus value that DC cell is obtained under different loading speeds using conventional method and method of the invention.
From figure it can be concluded that, using method of the invention under different compression distances and different loading velocities Under, the difference very little of Young's Moduli, different from the use of the obtained value of conventional method.
The rigidity value of the 3T3 cell and DC cell that obtain using characterizing method of the invention is given in table 1, is apparently glued Angle value, diffusion coefficient and comprehensive porosity.
The cell parameters value that table 1 is obtained with characterizing method of the invention
From table 1 it follows that various physical characteristics have apparent difference, and difference size for different cells Different, therefore, it is possible and insufficient to characterize the state of cell that a certain physical quantity is applied alone, and needs to integrate this four kinds of parameters to be total to With being described, physical state that can more comprehensively with accurate description cell.
The present invention is based on multilevel multiphase porous medium theories, it is contemplated that the presence of intracellular fluid phase proposes utilization The method that Hertz model obtains the new acquisition data of Young's Moduli and rigidity, perfectly solves one in conventional method Straight existing cell rigidity is easy to be pressed into the influence both of these problems of depth and loading speed, also discloses traditional vacation from side If deficiency.Meanwhile the invention proposes retouched with diffusion coefficient, Young's modulus, apparent viscosity and comprehensive porosity to integrate The method for stating cell physical state, the liveness that they may respectively with cell entirety, the state of cytoskeleton, cell liquid status And cell interior design feature is related.If this set system is applied in clinical medicine, potentially contribute to a variety of diseases Disease is understood, Clinics and Practices, it is also possible to provide a new measurement standard for the physiological status of cell.
Finally, method of the invention is only preferable embodiment, it is not intended to limit the scope of the present invention.It is all Within the spirit and principles in the present invention, any modification, equivalent replacement, improvement and so on should be included in protection of the invention Within the scope of.

Claims (7)

1. a kind of acquisition methods of Young's Moduli, comprising:
S1. based on the load force-time curve of cell surface to be measured, cell to be measured adding when the time is region infinity is obtained Carry power and compression distance;
S2. the loading force and compression distance based on cell to be measured when the time is region infinity, is calculated using Hertz model To the Young's modulus of cell to be measured;Wherein, S1 specifically:
Based on deformation-time graph of cell surface AFM probe to be measured, adding for cell surface to be measured is obtained using viscoelastic model Force-time curve is carried, loading force and compression distance of the cell to be measured when the time is region infinity are obtained;In the deformation- In the acquisition of time graph, data collection steps include: withdraw of the needle section, stand section, nearly needle section and slack strand;The data acquisition step Suddenly specifically:
S11. according to the force curve of cell to be measured, estimation obtains the position of probe Yu cell contact point to be measured, with the estimation position It is set to contact point, probe is lifted and is placed in the first height, is denoted as withdraw of the needle section, acquires the time value and AFM probe of withdraw of the needle section Deflection changing value;
S12. probe is stood in first height, is denoted as standing section, acquisition stands the time value and AFM probe of section Deflection changing value;
S13. it enables probe decline first distance with First Speed, to obtain the first compression distance in cell surface, is denoted as nearly needle Section, acquires the time value and AFM probe Deflection changing value of nearly needle section;
S14. it keeps probe constant in first compression distance, records the relaxation behavior of probe, be denoted as slack strand, acquisition relaxation The time value and AFM probe Deflection changing value of section.
2. the acquisition methods of Young's Moduli according to claim 1, which is characterized in that the data collection steps are also wrapped It includes:
Using S11-S14 as a cycle, multiple periods are repeated.
3. the acquisition methods of Young's Moduli according to claim 1 or claim 2, which is characterized in that the First Speed is at least For 10 μm/s.
4. a kind of characterizing method of cell physical state, comprising: use Young's modulus, apparent viscosity and diffusion coefficient comprehensive characterization Cell physical state;Wherein, the Young's modulus is the measurement using Young's Moduli described in any one of claim 1-3 Method obtains.
5. the characterizing method of cell physical state according to claim 4, which is characterized in that the apparent viscosity is based on power Benefit requires the curve of slack strand described in the measurement method of Young's Moduli described in any one of 1-3, utilizes viscoelastic model It is fitted acquisition;
And/or
The diffusion coefficient is relaxation described in the measurement method based on Young's Moduli described in any one of claim 1-3 The curve of section, is fitted acquisition using porous media model.
6. the characterizing method of cell physical state according to claim 4, which is characterized in that further include: use comprehensive hole Degree combines Young's modulus, apparent viscosity and diffusion coefficient comprehensive characterization cell physical state;Wherein, the comprehensive porosity utilizes Single bore diameter porous MEDIUM THEORY, which calculates, to be obtained.
7. a kind of mesoporous elastic or rigidity the characterizing method of cell, comprising: use cell poplar described in any one of claim 1-3 The acquisition methods of family name's modulus obtain Young's Moduli, to characterize the mesoporous elasticity or rigidity of cell.
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* Cited by examiner, † Cited by third party
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CN109269892B (en) * 2018-11-14 2020-08-11 燕山大学 Method and system for measuring elastic modulus of polymer
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101063646A (en) * 2006-04-24 2007-10-31 香港理工大学 Method for testing and determining material or organizational Yang modulus and poisson ratio by impression
CN102608360A (en) * 2011-01-19 2012-07-25 国家纳米科学中心 Representation method for cell microdomain flexibility
CN103674813A (en) * 2013-09-22 2014-03-26 中国科学院电子学研究所 Method for measuring Young modulus of single cell based on micro-fluidic technology
CN106199078A (en) * 2016-06-27 2016-12-07 上海交通大学 A kind of active somatic cell surface topography atomic force microscope quick accurate Characterization method

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040133362A1 (en) * 2002-10-21 2004-07-08 Emit Systems Co. Method for significantly increasing computational speed, accuracy and versatility of electromagnetic reconstruction of shapes and composition of complex targets containing lossy materials

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101063646A (en) * 2006-04-24 2007-10-31 香港理工大学 Method for testing and determining material or organizational Yang modulus and poisson ratio by impression
CN102608360A (en) * 2011-01-19 2012-07-25 国家纳米科学中心 Representation method for cell microdomain flexibility
CN103674813A (en) * 2013-09-22 2014-03-26 中国科学院电子学研究所 Method for measuring Young modulus of single cell based on micro-fluidic technology
CN106199078A (en) * 2016-06-27 2016-12-07 上海交通大学 A kind of active somatic cell surface topography atomic force microscope quick accurate Characterization method

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
Determination of Elastic Moduli of Thin Layers of Soft Material Using the Atomic Force Microscope;Emilios K. Dimitriadis et al.;《Biophysical Journal》;20020531;第82卷;2798-2810
Evaluation of the influence of growth medium composition on cell elasticity;Mehdi Nikkhah et al.;《Journal ofBiomechanics》;20111231;762-766
Nu'ria Gavara et al..Determination of the elastic moduli of thin samples and adherent cells using conical atomic force microscope tips.《Nature Nanotechnology》.2012,733–736.
原子力显微镜在细胞力学特性研究中的进展;马斌 等;《微纳电子技术》;20140930;第51卷(第9期);593-597
基于AFM的临床原代细胞机械特性测量研究进展;李密 等;《中国科学: 生命科学》;20161114;第46卷(第12期);1370-1381
头颈部组织样品微尺度力学的原子力显微镜检测;王洲 等;《影像科学与光化学》;20160531;第34卷(第3期);288-296

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