CN205719867U - A kind of Mechanobiology coupling testing system - Google Patents

A kind of Mechanobiology coupling testing system Download PDF

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CN205719867U
CN205719867U CN201620106353.4U CN201620106353U CN205719867U CN 205719867 U CN205719867 U CN 205719867U CN 201620106353 U CN201620106353 U CN 201620106353U CN 205719867 U CN205719867 U CN 205719867U
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light path
sample
biological sample
mechanobiology
cabin
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杨磊
刘浩然
白艳洁
杨惠林
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Suzhou University
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Suzhou University
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Abstract

The utility model provides a kind of Mechanobiology coupling testing system, it is characterized in being carried out high-resolution to material sample and biological sample interface immediately measure in situ by lower light path system, upper light path system, biochemical culture system, obtain the biological signals of interface mechanics and synchronization, and by results needed is obtained to the synthesis of signal and Treatment Analysis.Material sample that the utility model can be formed for any base material sample and any biological sample and biological sample interface, it is achieved with biological signals, high-resolution original position is carried out to mechanics simultaneously and immediately measures.

Description

A kind of Mechanobiology coupling testing system
[technical field]
The utility model relates to biotechnology and biomedical engineering field, is specifically related to a kind of Mechanobiology coupling Close test system.
[background technology]
In the clinical intervention and treatment of modern medicine, embedded type medicine equipment and artificial material have become as quick growth Great demand.But, as a example by orthopaedic disease, orthopaedics implant and artificial joint material are still faced with a series of being stranded Disturb the worldwide problem of people's many decades, such as prosthetic loosening, attrition and attack, stress fatigue and inefficacy and adjoint life Reason and pathological symptom.Problem above can be summarized as the mechanics mismatch (effect) of rigidity embedded material and tissue near interface substantially Result.But up to the present, the biological sample such as cell or tissue and material surface mechanics adaptation state (or mechanics phase interaction With) very difficult laboratory facilities measure or characterize, substantially can only be estimated by theoretical modeling and calculating.
For example, the method for the mechanical state between biological sample and material sample such as conventional at present measurement cell or tissue Have:
(1) AFM Atomic force microscopy
The critical component of AFM is the probe of nano-scale, when needle point is scanned on material sample surface When, sample can make cantilever bend with the active force of needle point, and order is deflected by the laser beam at the cantilever back side, by light electric-examination Survey device to detect, obtain surface topography image.In the mechanics of biological sample detects, AFM is commonly used to measure The viscoelasticity of the biological sample (such as cell, tissue etc.) of material sample surface adhesion, hardness and rigidity, biological sample surface are joined Body and the Interaction Force etc. of material acceptor.
(2) optical tweezer technology Optical tweezers
Can produce the power of 1-200pN when strong illumination is at minimum place, therefore laser gathering can form ligh trap, small items Being bound in by optical pressure at ligh trap, mobile beam can make small items move with ligh trap.Therefore this method may be used for Pearl (being made up of material interested) for example, is coated with by power Biological measurement by fibronectin, and therefore pearl can stick to On the biological samples such as cell, moved by Beam Control pearl, by detecting the displacement of pearl, biological sample rigidity can be obtained And the relevant information with material surface interactions.
(3) magnetic bead microflow control technique Magnetic bead microrheometry
In fluent material, fibronectin is utilized to be coated with paramagnet pearl, can be by biological samples such as pearl and cells Skeleton or part are joined directly together.Pearl is placed in magnetic field, can be observed, by light microscope, the shifting that pearl is caused by magnetic field Dynamic, the relevant information of available displacement and active force, with this mechanical property judging biological sample and mutual with fluent material Active state.
(4) technology Micropipette aspiration sucked by micro-pipe
The pipette that internal diameter is 1-10um is carried out contacting with cell and suction is provided, under the microscope direct observation of cell Deformation and movement.This technology can be used for the Biomechanics test of neutrophil leucocyte, red blood cell and outer hair cells, especially suitable Test for mammalian erythropoietin.
(5) tractive force microtechnic Traction force microscopy
The contraction that intracellular actin cytoskeleton produces is delivered to extracellular matrix via talin, can cause elastic substrates Deformation, tractive force microtechnic utilizes this deformation, substrate phosphor pattern before and after shooting deformation, and extracts areal deformation letter Breath, thus calculate the traction field of force of cell.
Prior art has the disadvantage in that
Multiple cells (generally less than 10) can be tested simultaneously under low cell adherence density by tractive force microtechnic simultaneously The mechanics calculating cell with material interacts, but cannot be at high-cell density (measuring hundreds of cell) bar for example simultaneously Implement under part, it is impossible to the tissue of test monoblock or biological sample, also cannot survey on rigid or opaque base material Amount, and when measurement, it is impossible to biology test is carried out to cell, it is impossible to obtain pattern and the biological signals of cell or tissue. Additionally, the method need material sample (i.e. substrate) possess special appearance (such as columnar arrays or micro-sphere array) and fluorescence or other Optical markings process.
AFM, optical tweezer technology, magnetic bead microflow control technique, micro-pipe suck technology every time can to single or several carefully Born of the same parents, and the tissue sample of micron-scale carries out biomethanics measurement, but cannot conditions of high cell density and to millimeter, centimetre The biological sample of size measures.And these methods are not the interaction of directly detection cell and material, but directly The mechanical state of detection cell, then calculated or simulate mechanics interaction or the mechanics adaptation obtaining cell and material by theory State, is not therefore the instant measurement in situ of mechanical signal truly.In addition, AFM speed is slow, survey every time Measure time-consuming a few minutes, it is impossible to realize instant measurement, and optical tweezer technology, magnetic bead microflow control technique, micro-pipe suck technology also cannot be Measurement carries out immediate observation in situ simultaneously to biological sample pattern or other biological signal.
[utility model content]
For above-mentioned deficiency and the restriction of prior art, the utility model provides a kind of Mechanobiology coupling measurement system System, is characterized in being carried out material sample with biological sample interface by lower light path system, upper light path system, biochemical culture system High-resolution instant measurement in situ, obtains the biological signals of interface mechanics signal and synchronization, and can be by the synthesis to signal Obtain biomethanics or power biological information with Treatment Analysis.The utility model can for the material sample of any substrate with Greatly any biological sample of cm size, including arbitrarily adhere to the cell of density or material sample that microbiological specimens is constituted with Biological sample interface, it is achieved the biological signals of mechanics and synchronization is carried out high-resolution original position, immediately measures.
A kind of Mechanobiology coupling testing system provided by the utility model, comprising: lower light path system, upper light path system System, biochemical culture system;Described lower light path system is for obtaining the power of material sample and biological sample interface in test process Learning signal, lower light path system includes optical strain sensor, light beam steering device and light path calibration system;Described optical strain senses Device is provided laser beam and is irradiated material sample burnishing surface by the turnover of light beam steering device, adjusts through light path calibration system After whole and calibration, the light beam returning after the reflection of material sample burnishing surface is caught, it is thus achieved that in situ, instant mechanics letter Number;Described upper light path system for carrying out immediate observation in situ in test process to biological sample, it is thus achieved that the biological sample of synchronization The biological signals of the pattern of product, upper light path system includes Visible imaging system and fluoroscopic imaging systems, described fluorescence imaging System includes fluorescence microscope;Described biochemical culture system is used for producing and keep the normal culture environment of biological sample, and ensures Described culture environment all-the-time stable when test, biochemical culture system includes cultivating atmosphere source of the gas, humidifier, culture dish, cultivation Cabin, temperature control system and sampling system, wherein cultivate atmosphere source of the gas and be connected to cultivate cabin, temperature control system through humidifier It is respectively connecting to cultivate cabin with sampling system.
Preferably, described optical strain sensor includes laser generator and CCD camera;Described laser generator produces Through the reflection of sample burnishing surface after radiating laser beams, return optical strain sensor;Described CCD camera catch return laser beam with Just original position, the mechanical signal of instant sample interface are obtained.
Preferably, light path calibration system is used for adjusting and calibrate light path to adapt to sample position, described light path calibration system Including support, cultivation cabin pallet, culture dish pallet and positioner.
Preferably, described light path can by light beam steering device, cultivate cabin pallet and set spacing from and angle be adjusted And light beam steering device, the distance cultivated between cabin pallet and support and angle are fixed after the adjustment, can be filled by positioning after fixing Put and sample position is finely adjusted.
Preferably, described biochemical culture system can keep in making described cultivation cabin stable temperature, relative humidity and Cultivate atmosphere level.
Preferably, described sampling system includes micro-injection pump, syringe or injector, is used for controlling biological sample or training Support base dripping quantity.
The advantage of the application includes: be applied to any base material sample of arbitrary surfaces pattern, any biological sample is appointed Meaning adheres to the material sample under density conditions and mechanics and the biological signals at biological sample interface are measured;Can be to macro-scale The large number of biological sample population of (full-size is Centimeter Level) or tissue are studied;And can be right under the physiological condition of simulation The interface of material sample and biological sample carries out high-resolution instant measurement in situ, it is thus achieved that the biological signals of mechanics and synchronization; Lower light path system ensures that system can carry out high-resolution in-situ mechanical test to material sample and biological sample interface;Upper light path system Guarantee system carries out instant biology test to material sample and biological sample interface, biological to the pattern and other of biological sample Learn signal to characterize;Mechanics and the biological signals of in-situ synchronization can be obtained, by analyze data in the range of special time, Image, obtains material sample and the state of biological sample and the mode of interaction and information;Can be to carrying out even under biological sample Continuous instant test, biological sample is cultivated and external environment condition isolation, it is achieved the cultivation under physiological condition;And by expanding lower light path Light path calibration system in system and the sampling system in biochemical culture system, improve test efficiency, accuracy, stability and Ease for operation.
[brief description]
With detailed description of the invention, the utility model is described in further detail below in conjunction with the accompanying drawings.
Fig. 1 is Mechanobiology coupling testing system structure principle chart described in the utility model embodiment.
Fig. 2 is the lower light path system schematic diagram of Mechanobiology coupling testing system described in the utility model embodiment.
Fig. 3 is the cultivation cabin pallet schematic diagram of Mechanobiology coupling testing system described in the utility model embodiment.
Fig. 4 is the culture dish pallet schematic diagram of Mechanobiology coupling testing system described in the utility model embodiment.
Fig. 5 is the positioner schematic diagram of Mechanobiology coupling testing system described in the utility model embodiment.
Fig. 6 is the sampling system of Mechanobiology coupling testing system described in the utility model embodiment.
Fig. 7 (1) to Fig. 7 (2) is obtained by Mechanobiology coupling testing system described in the utility model embodiment Experimental result example.
[detailed description of the invention]
As the utility model preferred embodiment, provide a kind of Mechanobiology coupling testing system, as Shown in Fig. 1-6.Fig. 1 is this Mechanobiology coupling testing system structure principle chart.This system is by lower light path system A, upper light path System B, biochemical culture system C composition.Lower light path system A is for obtaining interface mechanics signal in test process;Upper light path system System B carries out immediate observation in situ in test process to material sample, it is thus achieved that the biology letter of the pattern of the biological sample of synchronization Number;Biochemical culture system C is used for producing and keep biological sample normally to cultivate or growing environment.
As shown in Figure 1, Figure 2, shown in Fig. 3, Fig. 4, Fig. 5, lower light path system A specifically includes: optical strain sensor the 1st, light beam turns Folding device 2 and light path calibration system 3.Optical strain sensor 1, with laser generator, provides light beam to material by light path system Sample is irradiated, and catches the light beam returning after material sample reflection, it is thus achieved that in situ, instant mechanical signal; Light beam steering device 2 is level crossing;Light path calibration system 3 includes that the 10th, support cultivates cabin pallet the 11st, culture dish pallet, positioner, Light path can by light beam steering device, cultivate cabin pallet and set spacing from and angle is adjusted and light beam steering device, cultivation Distance between cabin pallet and support and angle are fixed after the adjustment, can be carried out material sample position by positioner after fixing Fine setting.Cultivate cabin pallet as it is shown on figure 3, be made up of two c-type aluminium alloy devices, adjustable device pitch from and set spacing from Place different model sterile culture cabin.Described support is assembled by the guide rail containing groove.As shown in Figure 4, culture dish pallet is led by height Heating rate aluminium alloy is made, it is ensured that in cultivating cabin, homogeneous temperature is constant.Light path can be by light beam steering device, cultivation cabin pallet and support Spacing and angle are adjusted.Distance and angle are adjusted rear fixing, only need to change material sample and be not necessarily to when testing every time Again carry out light path calibration, simplify testing process, improve efficiency.As it is shown in figure 5, positioner is rack-mount, in order to admittedly Surely cultivate cabin pallet, and pass through device and the spring 12 (1) to 12 (7) cultivated between the pallet of cabin and knob 13 (1) to 13 (3) fine setting Position in X, Y-direction.
Upper light path system B includes: Visible imaging system and fluoroscopic imaging systems 4, wherein fluoroscopic imaging systems 4 includes glimmering Light microscope.As shown in Figure 1, Figure 3, the Visible imaging system of upper light path system and fluoroscopic imaging systems 4 to material sample with The interface of biological sample carries out instant biology test, it is thus achieved that the biological sample biological signals of synchronization.
Biochemical culture system C includes cultivating atmosphere source of the gas the 5th, humidifier the 6th, culture dish, cultivation cabin the 7th, temperature control system the 8th, Sampling system 9, it is possible to provide stable biological sample condition of culture: stable temperature, relative humidity and atmosphere level, it is ensured that biological The normal of sample is cultivated and growing environment.Wherein cultivate cabin and fluoroscopic imaging systems connected by flexible clear materials and seals, Fluoroscopic imaging systems camera lens retractable, the biological sample growing environment that cultivating cabin is provided will not change, and with outward Portion is environmentally isolated, it is achieved sterile culture.Sampling system 9 as shown in Figure 6, including micro-injection pump the 14th, syringe or sample injector 15. Micro-injection pump by advancing fixed range control biological sample dripping quantity when sample introduction.
Fig. 7 is the experimental result example that this experiment obtains.Wherein Fig. 7 (1) is the interface mechanics letter that lower light path system obtains Number, 7 (2) is the biological signals of the synchronization that upper light path system obtains.
In Fig. 7 (1), X-axis is time/s, and Y-axis is apparent strain/STRESS VARIATION:
In 0-3700s, system no-load running;
At 3700s, drip biological sample;
At 4100s, it appeared that direct stress (strain) signal, show that material sample is interacted by biological sample;
At 4250s, direct stress (strain) reaches maximum, starts reversion;
At 4300s, negative stress (strain) signal occurs, show that material sample be there occurs by the interaction of biological sample Change;
After 4400s, stress (strain) signal is gradually restored to zero, shows the phase interaction by biological sample for the material sample With fading away.
Fig. 7 (2) is the biological signals that upper light path system obtains when 4100s and 4300s respectively.
Be applied to any base material sample of arbitrary surfaces pattern, any biological sample arbitrarily adheres under density conditions The mechanics at material sample and biological sample interface and biological signals measurement;Can be to macro-scale (full-size is Centimeter Level) Large number of biological sample population or tissue are studied;And can be under the physiological condition of simulation, to material sample and biological sample Interface carries out high-resolution instant measurement in situ, it is thus achieved that the biological signals of mechanics and synchronization;Lower light path system ensures that system can High-resolution in-situ mechanical test is carried out to material sample and biological sample interface;Upper light path system ensure system to material sample with Biological sample interface carries out instant biology test, characterizes the pattern and other biological signals of biological sample;Can obtain The mechanics of in-situ synchronization and biological signals, by analyzing data in the range of special time, image, obtain material sample with The mode of the state of biological sample and interaction and information;Can be to carrying out continuously instant test under biological sample, biological sample Product are cultivated and external environment condition isolation, it is achieved the cultivation under physiological condition;And by expanding out the light path calibration in lower light path system Sampling system in system and biochemical culture system, improves efficiency, accuracy, stability and the ease for operation of test.
Above example is merely to illustrate the utility model, and is not limitation of the utility model, relevant technical field Those of ordinary skill, in the case of without departing from spirit and scope of the present utility model, can also make a variety of changes and become Type, therefore all equivalent technical schemes fall within category of the present utility model, and scope of patent protection of the present utility model should be by Claim limits.

Claims (6)

1. a Mechanobiology coupling testing system, it is characterised in that include: lower light path system, upper light path system, biochemical training The system of supporting;Described lower light path system is used for obtaining the mechanical signal of material sample and biological sample interface in test process, under Light path system includes optical strain sensor, light beam steering device and light path calibration system;Optical strain sensor provides laser light Material sample burnishing surface is simultaneously irradiated by bundle by the turnover of light beam steering device, after light path calibration system call interception and calibration, The light beam returning after the reflection of material sample burnishing surface is caught, it is thus achieved that in situ, instant mechanical signal;Described upper light path System for carrying out immediate observation in situ in test process to biological sample, it is thus achieved that the biology of the pattern of the biological sample of synchronization Learning signal, upper light path system includes Visible imaging system and fluoroscopic imaging systems, and described fluoroscopic imaging systems includes that fluorescence shows Micro mirror;Described biochemical culture system is used for producing and keeping the normal culture environment of biological sample, and ensures that described culture environment exists All-the-time stable during test, biochemical culture system includes cultivating atmosphere source of the gas, humidifier, culture dish, cultivation cabin, temperature control system And sampling system, wherein to cultivate atmosphere source of the gas and be connected to cultivate cabin through humidifier, temperature control system and sampling system are respectively It is connected to cultivate cabin.
2. Mechanobiology coupling testing system according to claim 1, it is characterised in that described optical strain sensor Including laser generator and CCD camera;Through the reflection of sample burnishing surface after the radiating laser beams that described laser generator produces, return Optical strain sensor;Described CCD camera catches the laser beam returning to obtain the mechanics letter of original position, instant sample interface Number.
3. Mechanobiology coupling testing system according to claim 1, it is characterised in that light path calibration system is used for adjusting Whole and calibration light path is to adapt to sample position, and described light path calibration system includes support, cultivates cabin pallet, culture dish pallet and fixed Position device.
4. Mechanobiology coupling testing system according to claim 3, it is characterised in that described light path can pass through light beam Turner, cultivate cabin pallet and set spacing from and angle is adjusted and light beam steering device, cultivates between cabin pallet and support Distance and angle fix after the adjustment, fixing after by positioner, sample position can be finely adjusted.
5. Mechanobiology coupling testing system according to claim 1, it is characterised in that described biochemical culture system makes Stable temperature, relative humidity can be kept in described cultivation cabin and cultivate atmosphere level.
6. Mechanobiology coupling testing system according to claim 1, it is characterised in that described sampling system includes micro- Amount syringe pump, syringe or injector, be used for controlling biological sample or culture medium dripping quantity.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019128766A1 (en) * 2017-12-27 2019-07-04 大连理工大学 Experimental system and method applicable to precise regulation of macromolecular crystallization processes

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019128766A1 (en) * 2017-12-27 2019-07-04 大连理工大学 Experimental system and method applicable to precise regulation of macromolecular crystallization processes
US11452948B2 (en) 2017-12-27 2022-09-27 Dalian University Of Technology Experiment system and method for accurate controlling of macromolecular crystallization process

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