CN106503423A - Based on the microvascular implantation seed magnetic targeted experiment in vitro device and method of infiltration - Google Patents
Based on the microvascular implantation seed magnetic targeted experiment in vitro device and method of infiltration Download PDFInfo
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Abstract
The present invention discloses a kind of being based on and permeates microvascular implantation seed magnetic targeted experiment in vitro device and method, and the device includes conveyor module, external magnetic field module, targeting district, seed suspension and magnetic drug-carrying particle suspension.Conveyor module conveying seed suspension and magnetic drug-carrying particle suspension；In targeting district periphery, capture is once transported to the seed of targeting district and excites seed to produce local auxiliary magnetic field external magnetic field module loading, and then under external magnetic field with auxiliary magnetic field effect captures second-pumping to the magnetic drug-carrying particle of targeting district；Targeting district simulation blood capillary and its cancerous issue of surrounding；Seed suspension and the carrier fluid that magnetic drug-carrying particle suspension is seed and magnetic drug-carrying particle respectively.The experimental technique of seed and magnetic drug-carrying particle trapping rate experiment in vitro is devised, the method can simulate human canceration's tissue and its microvascular Penetration Signature, while considering blood properties, test the optimized parameter for obtaining and data supporting can be provided for clinical practice.
Description
Technical field
The present invention relates to a kind of experiment in vitro device of magnetic targeted system, especially a kind of based on capillary permeability effect
It is implanted into the experiment in vitro device and its experimental technique of the magnetic targeted system of seed auxiliary.
Background technology
Cancer treatment method typically has：Excision, radiotherapy, chemotherapy.Need in chemotherapy by improving drug dose
Increasing the drug level of cancerous region to reach therapeutic effect, this inevitable normal tissue causes toxic and side effects to mode.Medicine
Targeted therapy is specially treated cancer therapy drug under the guiding of stereotactic conditions, is selectively transported in human body
Focal area, can thus change medicine and be distributed in vivo, while focal zone drug level is improved, reduce normal structure medicine
Thing concentration is reducing toxic and side effects.Magnetic targeted as one of most promising research direction in treatment of cancer, with improving canceration
Tissue regions local cancer therapy drug concentration, reduces the advantage to health tissues toxic and side effects.Its principle be by magnetic carrier,
Under external magnetic field, internal specific part is directly targeted by magnetic and medicated, improves target site drug level, reduce medicine and align
The Side effect that often organizes.But two point defects are still suffered from application：1) due to external magnetic field produce weak magnetic field force not
Can play a leading role in tissue fluid, blood etc. are to the active force of magnetic drug-carrying particle, and make magnetic drug-carrying aggregation of particles with
Retention effect is not notable；2) delivery method generally can only be larger to treating the effect of superficial cancerous issue, when
When canceration area is located at skin following deep place, Targeting Effect is poor, and can with the increase Targeting Effect of depth can drastically under
Drop.For overcoming the defect of traditional magnetic targeted method, there is related researcher to propose and be implanted into the magnetic and medicated of auxiliary magnetic seed
The concept of targeted therapy, i.e., on the premise of using external magnetic field, help magnetic drug-carrying particle in targeting by being implanted into magnetic seed
Area is attracted and is detained.The principle of the method is separated from High-gradient Magnetic：The magnetic seed that targeting district is implanted into is in external magnetic field
Under be magnetized, the size of the auxiliary magnetic field for not only producing is bigger than external magnetic field, while changing external magnetic field and generating bigger magnetic
Field gradient, proportional to magnetic field size and magnetic field gradient due to acting on the magnetic field force on magnetic drug-carrying particle, so in outer magnetic
Under field and auxiliary magnetic field dual function, the magnetic field force being added on magnetic drug-carrying particle strengthens therewith, and magnetic drug-carrying particle is in outer magnetic
It is attracted under field and auxiliary magnetic field collective effect and is trapped in targeting district.
In the achievement that has studied：1) invention " magnetic composite and the method for treating cancer " is (open (public
Accuse) number：CN1548159), the application in radiotherapy in magnetic composite is paid close attention to, a kind of new magnetic is prepared for multiple
Condensation material simultaneously devises application process of the composite in radiotherapy；2) invention " is used for magnetic and medicated thing using permanent-magnet
The method and device of reason targeting positioning " (open (bulletin) number：CN102429857A), it is absorbed in the optimization of magnetic field device, proposes
A kind of new permanent-magnet arrangement is magnetic and medicated to position, and which is especially fitted for the medicine positioning at middle depth position
With；3) utility model " the non-invasive magnetic steering device for promoting agent-cell to assemble to deep tissue targeting " (open (bulletin)
Number：CN203342198U), equally focus is placed on magnetic field device, devises a kind of electromagnet of magnetic field deep focus, with reality
Positioning of the existing medicine in deep layer；4) utility model " a kind of targeting drug-delivery system of antitumor magnetic nano-particle medicine " is (open
(bulletin) number：CN204016940U), a kind of targeting drug-delivery system has been designed and developed, the device can reduce magnetic and medicated stream
Dynamic, and medicine is concentrated on tumor locus preferably.
Above achievement in research all presents the using value in terms for the treatment of of cancer, but not from magnetic targeted system
Problem from the aspect of the overall situation, focuses simply on certain a part of (the such as magnetic field device) of system.Due to the complexity of body tissue,
Diversity between cancerous issue and health tissues etc. can all affect magnetic drug-carrying particle in the aggregation of targeting district, therefore body
In the property of tissue must be considered in.In addition in above achievement, 1) in be research with regard to radiotherapy, 2), 3), 4) be all based on nothing
The research of auxiliary magnetic seed medicine targeting mode is implanted into, it is concluded that being also qualitatively in the application of achievement in research.?
It is implanted into before aiding in magnetic seed magnetic targeted system to be put to clinical practice, in order to safety and reliability considers, it is necessary to first from body
Exterior-excess check-in handss, on the premise of obtaining experimental data support, just progressively can launch.
At present, in the magnetic and medicated targeting ill vitro test method for being implanted into seed auxiliary, for microvascular simulation mainly
Internal diameter is adopted for hundreds of micron of glass tubing, or the porous material for being covered with micro-meter scale hole using inside substitutes body
The blood capillary of random distribution in tissue.Both approaches all compare actual blood capillary (internal diameter on yardstick：6～10 μm) big two
The order of magnitude, in addition the former ignores capillary permeability effect completely, and the latter simply considers that the blood capillary of random distribution in body is produced
Population effect, do not make research for single blood capillary.In terms of magnetic drug-carrying particle and its carrier fluid, simply with single go from
Sub- water does not consider the actual nature of blood as carrier fluid, while not adding other particles in the suspension of magnetic drug-carrying particle
To simulate the impact of the erythrocyte in blood.Although closed using the rare earth material with very big remanent magnetism in the selection of outer magnetizing mediums
Gold is (such as：Neodymium iron boron), but be all rectangular configuration in appearance, Distribution of Magnetic Field has limitation, and the decay in distal end is very big.
Content of the invention
Technical problem：In order to improve accuracy of the experiment in vitro in simulation truth, glass tubing and porous is overcome
Seepage material yardstick is big and does not consider to permeate, and the defect of blood properties impact ignored by magnetic drug-carrying particle and its carrier fluid, with
When in order to reach outer magnetizing mediums distal end still have comparatively dense Distribution of Magnetic Field, the present invention provide a kind of consideration infiltration experiment
Device and method, the device can not only simulate the property of truly microvascular structure and blood well, and can solve
Violent decay of the outer magnetizing mediums in distal end, while obtain one group of experiment parameter for making capture rate optimum for clinic by experiment in vitro
Application provides data supporting.
Technical scheme：The present invention is that a kind of being based on permeates microvascular implantation seed magnetic targeted experiment in vitro device, the dress
Put including conveyor module, targeting district, external magnetic field module, seed suspension, magnetic drug-carrying particle suspension；Wherein, conveyor module
Comprising dual pathways syringe pump, the first syringe, the second syringe, glass tubing are exported with ware, two of dual pathways syringe pump are collected
End connects the first syringe and the second syringe respectively, the sub- suspension of the load that is magnetic in wherein the first syringe powder, the second injection
The outfan connection for having seed suspension or cleanout fluid, two syringes in device is followed by glass tubing；Targeting district is that a centre is opened
The bar-shaped porous media material two ends connection glass tubing for having through hole is constituted；External magnetic field module is located at by targeting district, comprising one forever
Magnet, with the fixture that can control distance between permanent magnet surfaces and targeting district axis；In seed suspension comprising magnetic seeds,
Deionized water, sodium lauryl sulphate and glycerol；Include magnetic drug-carrying particle, deionization in magnetic drug-carrying particle suspension
Water, sodium lauryl sulphate and glycerol；Cleanout fluid includes ionized water, sodium lauryl sulphate and glycerol；The experimental provision
Effect be in vitro research be implanted into auxiliary magnetic targeted system in magnetic drug-carrying particle trapping rate influence factor and its change rule
Rule.
The hole mean radiuss of the inner homogeneous distribution of the bar-shaped porous media material adopted by described targeting district are for 50
～250nm, porosity are 75%～90%, and define permeability parameters and describe the concept nondimensionalization of permeability inside difference
The osmotic effect of the material of structure；The external structure size of bar-shaped porous media material is simultaneously：Diameter D=10mm, length l
=50mm, a diameter of 50 μm of the through hole that is opened in bar-shaped porous media material axis.
The material of the permanent magnet in the external magnetic field module is neodymium iron boron Nd2Fe14B rare earth permanent-magnetic materials, structure are cylinder
Type, magnetic direction radial magnetizing.
Outside targeting district, the fixture in external magnetic field module is by fixed permanent magnet, running target to external magnetic field module loading
Change distance between permanent magnet surfaces and targeting district axis to the mode in area, distance change scope is 0～7cm.
Described seed suspension is will to obtain the ferroso-ferric oxide particle of hydrophilic group through surface modification, fully dispersed
The stable suspension for being formed in deionized water；The mean diameter of seed is 20nm, and adds sodium lauryl sulphate wherein
SDS is used as activating agent, and ensures that the concentration of SDS is 50mM, finally with the glycerol that volume ratio is 5% as viscosity additive.
Described magnetic drug-carrying particle suspension is will to obtain the ferroso-ferric oxide particle of hydrophilic group through surface modification,
The fully dispersed stable suspension for being formed in deionized water；The mean diameter of magnetic drug-carrying particle between 50～400nm, and
Sodium lauryl sulphate SDS is added wherein as activating agent, and ensures that the concentration of SDS is 50mM, be finally 5% with volume ratio
Glycerol as viscosity additive.
In cleanout fluid, the concentration of sodium lauryl sulphate is 50mM, and the volume ratio of glycerol is 5%.
Being included based on the experimental technique for permeating microvascular implantation seed magnetic targeted experiment in vitro device for the present invention is following
Step：
1) configuration concentration be 200mg/L, the seed suspension of 400mg/L, 600mg/L, 800mg/L, 1000mg/L；
2) configuration concentration is respectively 200mg/L, 400mg/L, 600mg/L, 800mg/L, 1000mg/L magnetic drug-carrying particle
Suspension, magnetic drug-carrying particle mean radiuss be 50nm, 150nm, 250nm, 350nm, 400nm；
3) cleanout fluid is configured；
4) weigh the quality of dry collection ware, arrange cylindrical permanent magnet surface and bar-shaped porous media material axis it
Between distance be 1cm-5cm；
5) the bar-shaped porous media material that permeability parameters are 1 is soaked completely with cleanout fluid；
6) whole experiment in vitro device is connected, the cleanout fluid for extracting certain volume with the second syringe, and be injected into
In the fluid passage of experimental provision until end has liquid to flow out；
7) constant flow rate for arranging dual pathways syringe pump makes flow rate of liquid in the bar-shaped hole dielectric material intermediate throughholes of targeting district
For 20mm/s, magnetic seeds suspension 10mL is extracted and on the lower channel of syringe pump with the second syringe, connect glass
Glass pipe；It is 200mg/L magnetic drug-carryings particle suspension 20mL and installed in the upper logical of syringe pump that concentration is extracted with the first syringe
On road, glass tubing is connected；
8) start syringe pump lower channel, start to inject seed suspension up to terminating, from the kind that whole experimental provision flows out
Sub- suspension is collected with beaker；Syringe pump upper channel is again started up, starts to inject magnetic drug-carrying particle suspension, from whole experiment
The magnetic drug-carrying particle suspension that device flows out is collected with the collection ware for weighing quality；
9) the cleanout fluid injection experimentses device of certain volume is extracted with the second syringe again, until liquid is from experimental provision
Flow out end；
10) will collect ware in collect magnetic drug-carrying particle suspension in liquid portion dry, and weigh wherein not by
The quality of the magnetic drug-carrying particle of capture；
11) capture rate is calculated：The quality of the magnetic drug-carrying particle of injection experimentses device is calculated according to concentration known with volume
Mi, according to the mass M for collecting Mass Calculation of the ware before and after experiment magnetic drug-carrying particle at largeo, calculate capture rate
12) said process three times is repeatedly performed with identical experiment parameter, seeks CE meansigma methodss；
13) repeat said process under other experiment parameters successively, until the experiment of all parameters is fully completed.
Beneficial effect：The magnetic targeted system of the implantation auxiliary magnetic seed that this experimental provision and method are related to, is produced by seed
Raw auxiliary magnetic field can solve violent decay of the outer magnetizing mediums in distal end, improve the capture rate of magnetic drug-carrying particle.And this
Experimental provision and method simulate the property of human canceration's tissue and its microvascular permeability and blood, while test yardstick connecing
Nearly truth, the experiment in vitro for therefore being carried out by the device simulation can be implanted in the magnetic targeted system of seed very well
Seed transporting in blood capillary with magnetic drug-carrying particle, the experimental data for drawing can be that following experiments in vivo is answered with clinical
With offer support.
Description of the drawings
The present invention is further described with reference to the accompanying drawings and examples.
Fig. 1 is shown as the principle schematic for being implanted into auxiliary magnetic seed magnetic targeted system.
Fig. 2 is shown as illustrating based on the principle for permeating microvascular implantation seed auxiliary magnetic targeted system experiment in vitro device
Figure.
Fig. 3 is shown as the principle schematic of targeting district partial cross section amplification.
Fig. 4 is shown as permanent magnet schematic diagram.
Have in figure：Dual pathways syringe pump 1, the first syringe 2, the second syringe 3, glass tubing 4, collection ware 5, seed are suspended
Liquid 6, magnetic drug-carrying particle suspension 7, targeting district 8, external magnetic field module 10, permanent magnet 10.1, cleanout fluid 11, conveyor module 12,
External magnetic field 13, the magnetic seed 14 being once injected, the secondary magnetic drug-carrying particle 15 being injected, cancerous issue 16, magnetic seed with
Blood flow 17.
Specific embodiment
The present invention be a kind of based on permeate microvascular be implanted into seed aid in magnetic targeted system experiment in vitro device, the dress
Put including conveyor module, external magnetic field module, targeting district, seed suspension and magnetic drug-carrying particle suspension, cleanout fluid.Wherein,
Conveyor module is used for conveying seed suspension with magnetic drug-carrying particle suspension to targeting district until the outside of whole device；Outer magnetic
The effect of field module is once to be transported to the seed of targeting district by external magnetic field capture by conveyer device and excite seed to produce
Local auxiliary magnetic field, and then attract under external magnetic field with auxiliary magnetic field effect and capture by conveyor module second-pumping to targeting district
Magnetic drug-carrying particle；Targeting district is the module for simulating human canceration's tissue microvascular and the cancerous issue around blood capillary；Kind
Sub- suspension produces local auxiliary magnetic field by being excited by external magnetic field；Magnetic drug-carrying particle suspension is magnetic drug-carrying particle
Carrier, while simulate the property of blood；Cleanout fluid rinses the fluid passage of experimental provision in experimentation.
The effect of the present invention is to simulate true cancerous issue and its blood capillary and blood properties in vitro, by changing outer magnetic
Medium simultaneously determines the injection rate of magnetic seeds and magnetic target medicine in the case of being implanted into seed, magnetic and medicated in targeting in order to describe
The capture effect in area, defines capture rate：
Wherein, MiIt is the gross mass of the magnetic drug-carrying particle for being transported to targeting district by conveyor module, MoFor at large
The quality of magnetic drug-carrying particle.Magnetic seeds by conveyer device by finite concentration with volume in experimentation are carried with magnetic
The sub- suspension of powder, is transported to targeting district according to the order of particle after first seed with certain flow velocity, is being added in the outer magnetic of targeting district
In the presence of the module of field, the magnetic seeds being initially injected are captured and excite generation local auxiliary magnetic field, the magnetic being injected into again
Property carry powder and be captured in the presence of external magnetic field and auxiliary magnetic field and be trapped in targeting district, part at large is with outstanding
Turbid liquid movement is to conveyor module end.
Conveyor module is made up of syringe pump, syringe, glass tubing, collection ware etc., and wherein syringe pump can be defeated with constant flow rate
Send seed or magnetic drug-carrying particle suspension.
Magnetic field source in external magnetic field module is all very high using remanence strength, magnetic energy product, coercivity, while can
The rare earth permanent-magnetic material for stablizing big field intensity is provided, the Distribution of Magnetic Field in order to change targeting district is designed to adjust permanent magnet and targeting
The fixture of distance between area.
Targeting district：Targeting district is the region that magnetic seeds and magnetic and medicated particle are directed capture.In order to simulate canceration group
The osmotic effect of wall of micrangium in the structure and properties that knits and cancerous issue, targeting district adopt the uniform nanoscale of internal random
The bar-shaped porous media material imitated biological tissue of hole, and through hole simulation blood capillary is opened on porous media material.
Seed suspension and magnetic drug-carrying particle suspension：Seed suspension and magnetic drug-carrying particle suspension are all to pass through
Cross the ferroso-ferric oxide particle that surface modification obtains hydrophilic group, the fully dispersed stable suspension for being formed in deionized water,
The mean diameter of seed is 20nm, and in order to meet experiment needs, the mean diameter of magnetic drug-carrying particle is between 50～400nm.
In order to simulate the property of true blood, in suspension, add the viscosity additive of certain volume ratio to change its viscosity, select third
Triol is viscosity additive, and the addition of glycerol is measured by capillary tube method.
Cleanout fluid：Cleanout fluid injection experimentses device before and after experiment, plays a part of cleaning liquid passage, is dodecyl
Sodium sulfate (SDS) and the deionized water mixed solution of glycerol.
For becoming apparent present disclosure, it is described further below in conjunction with the drawings and specific embodiments.
As shown in Figure 1 for being implanted into the principle schematic of auxiliary magnetic seed magnetic targeted system, auxiliary magnetic seed magnetic target is implanted into
Include three parts to system：1) external magnetic field 13, i.e., at a distance, the magnetic field of low gradient；2) the magnetic seed 14 being once injected, can be
Can be magnetized under external magnetic field and a high-gradient magnetic field is created near cancerous issue 16；3) the secondary magnetic being injected
Powder 15 is carried, i.e., is captured by high-gradient magnetic field under external magnetic field with internal auxiliary magnetic field effect and is trapped near cancerous issue
Pharmaceutical carrier.The capture step of cancer therapy drug is：1) magnetic seed is injected, magnetic seed enters blood capillary with blood flow 17, in canceration
In the presence of adjacent tissue external magnetic field device, magnetic seed is captured and is trapped near cancerous issue, and near cancerous issue
Produce auxiliary magnetic field.2) magnetic drug-carrying particle is injected, and magnetic drug-carrying particle is common in the auxiliary magnetic field that external magnetic field and magnetic seed are produced
It is captured under same-action.
It is the schematic diagram of experimental provision as shown in Figure 2, is respectively from left to right：Dual pathways syringe pump 1, the first syringe
2nd, the second syringe 3, glass tubing 4, collection ware 5, targeting district 8 and external magnetic field module 10, external magnetic field module loading is outside targeting district
Enclose.Due to affect capture rate factor have a lot, now with regard to concentration factor under the influence of capture rate test experiments example as follows：
(1) configuration concentration is ρsThe magnetic seeds suspension of=600mg/L, and the volume ratio by 5% adds glycerol；Will
Mean radiuss are that 150nm (or 50nm, 250nm, 350nm, 400nm) magnetic drug-carrying particle concentration is respectively ρnp=200mg/L,
The magnetic drug-carrying particle suspension of 400mg/L, 600mg/L, 800mg/L, 1000mg/L, and the volume ratio by 5% adds the third three
Alcohol；Sodium lauryl sulphate (SDS) solution of the configuration concentration for 50mM, same addition volume ratio are 5% glycerol, obtain by third
The cleanout fluid that triol is constituted with SDS.
(2) quality of dry collection ware is weighed, is arranged between cylindrical permanent magnet surface and simulation blood capillary axis
Apart from d=1cm (or 2cm, 3cm, 4cm, 5cm).
(3) it is that 1 (or 2,3,4,5,6, porous media material 7) soaks completely, this step with cleanout fluid by permeability parameters
Purpose is the effect for simulated human tissue liquid to magnetic drug-carrying particle in acquisition procedure.
(4) connect whole experiment in vitro device according to accompanying drawing, with syringe extract certain volume cleanout fluid, and by its
In the fluid passage of injection experimentses device until end has liquid to flow out.
(5) constant flow rate for arranging dual pathways syringe pump is 5.08mL/h, liquid flow in now targeting district simulation blood capillary
Speed is 20mm/s (or 1.5mm/s, 10mm/s, 30mm/s, 40mm/s)；Magnetic seeds suspension 10mL is extracted simultaneously with syringe
On the lower channel of syringe pump, glass tubing is connected；With syringe extract concentration be 200mg/L (or 400mg/L,
600mg/L, 800mg/L, 1000mg/L) magnetic drug-carrying particle suspension 20mL and installed in syringe pump upper channel on, connection
Good glass tubing.
(6) start syringe pump upper channel button, start to inject seed suspension until end, flows out from whole experimental provision
Seed suspension collected with beaker；Syringe pump lower channel button is again started up, starts to inject magnetic drug-carrying particle suspension, from
The magnetic drug-carrying particle suspension that whole experimental provision flows out is collected with the collection ware for weighing quality.Certain volume is extracted again
Cleanout fluid injection experimentses device, until liquid from experimental provision end flow to collect ware in.
(7) will collect ware in collect magnetic drug-carrying particle suspension in liquid portion dry, and weigh wherein not by
The quality of the magnetic drug-carrying particle of capture.
(8) capture rate is calculated：The quality of the magnetic drug-carrying particle of injection experimentses device is calculated according to concentration known with volume
Mi, according to the mass M for collecting Mass Calculation of the ware before and after experiment magnetic drug-carrying particle at largeo, count according to formula (1)
Calculate capture rate CE.
(9) said process three times is repeatedly performed with identical magnetic drug-carrying particle turbid liquid concentration, seeks CE meansigma methodss.
(10) the magnetic drug-carrying particle suspension for changing other concentration repeats said process, until the experiment under all concentration is complete
Portion completes.
Can be measured under variable concentrations by above procedure, the capture rate of magnetic drug-carrying particle, and then draw curve and be obtained
It is that clinical practice plays directive function to capture rate Changing Pattern.Simultaneously when other influences factor is studied, for example：External magnetic field factor
(being described with the distance between blood capillary axis is simulated by changing cylindrical permanent magnet surface)；Suspension is in simulation blood capillary
In flow velocity；The mean radiuss of magnetic drug-carrying particle；The permeability parameters of porous media.This covering device can be equally adopted, according to
Process like above is carrying out.When all magnetic drug-carrying particle trapping rates influence factor test experiments all after the completion of, you can
Changing Pattern of the capture rate under different affecting factors is inquired in terms of each, final choice is most viable, while capture rate is higher
Each influence factor parameter, provide important reference for clinical practice.
If accompanying drawing 3 is the enlarged section of targeting district local, when seed suspension is injected into experimental provision and moves to
During targeting district, under the effect of external magnetic field module, seed is captured and produces local auxiliary magnetic field；Then magnetic drug-carrying particle is suspended
Liquid is injected into experimental provision and moves to targeting district, magnetic drug-carrying particle quilt under the auxiliary magnetic field effect of external magnetic field and seed
Capture.9 internal random of porous media material that targeting district is adopted is dispersed with average diameter for 50～250nm nano apertures, its hole
Porosity is 75%～90%, and the power for being exactly osmotic effect in macroeffect due to the distinguishing reaction of internal structural properties is not
Same, can thus simulate the blood capillary and its surrounding tissue of different permeability.In order to meet experiment demand and fully simulate micro-
Tissue around blood vessel and blood capillary, the physical dimension of bar-shaped porous media is：Diameter D=10mm, spends l=50mm.Due to
The microvascular internal diameter of general human body is 8～10 μm, in order to simulate blood capillary to greatest extent under conditions of experiment is met, many
The through hole radius that is opened on the medium of hole is 25 μm (R=25 μm).For porous media osmotic effect power permeability general
Read to describe, and permeability parameters are defined by permeability nondimensionalization.In experimentation, porous media material two ends and glass tubing
4, magnetic seed 14 is entered in the through hole of porous media material through glass tubing with magnetic drug-carrying particle 15, and is caught on wall
Obtain.
Such as accompanying drawing 4, it is the schematic diagram of rare earth material permanent magnet, the rare earth material in the present invention specifically adopts neodymium iron boron
(Nd2Fe14B) rare earth permanent-magnetic material, while structure is that column type is (high with magnetic direction：50mm, diameter：30mm) radial magnetizing.
In order to change the distance between targeting district and permanent magnet, permanent magnet is fixed by self-made clamp, while the radial direction in permanent magnet
Mobile targeting district targeting district, makes the distance between permanent magnet surfaces and targeting district center change in the range of 0～7cm, so controls
Distribution of the external magnetic field processed in targeting district.
Claims (8)
1. a kind of based on the microvascular implantation seed magnetic targeted experiment in vitro device of infiltration, it is characterised in that：The device includes defeated
Send module (12), targeting district (8), external magnetic field module (10), seed suspension (6), magnetic drug-carrying particle suspension (7)；Wherein,
Conveyor module includes dual pathways syringe pump (1), the first syringe (2), the second syringe (3), glass tubing (4) and collection ware (5),
Two outfans of dual pathways syringe pump (1) connect the first syringe (2) and the second syringe (3), wherein the first syringe respectively
(2) load that is magnetic in powder is sub- suspension (7), has seed suspension (6) or cleanout fluid, two injections in the second syringe (3)
The outfan connection of device is followed by glass tubing (4)；Targeting district (8) is the bar-shaped porous media material (9) that a centre is provided with through hole
Two ends connection glass tubing (4) are constituted；External magnetic field module (10) is located at targeting district (8) side, comprising a permanent magnet (10.1), with energy
The fixture of distance enough between control permanent magnet surfaces and targeting district axis；Include magnetic seeds, deionization in seed suspension (6)
Water, sodium lauryl sulphate and glycerol；In magnetic drug-carrying particle suspension (7) comprising magnetic drug-carrying particle, deionized water, ten
Sodium dialkyl sulfate and glycerol；Cleanout fluid includes ionized water, sodium lauryl sulphate and glycerol；The effect of the experimental provision
It is that research in vitro is implanted into the influence factor of magnetic drug-carrying particle trapping rate and its Changing Pattern in auxiliary magnetic targeted system.
2. according to claim 1 based on microvascular implantation seed magnetic targeted experiment in vitro device is permeated, its feature exists
The hole mean radiuss of the inner homogeneous distribution of the bar-shaped porous media material (9) adopted in described targeting district for 50～
250nm, porosity are 75%～90%, and define permeability parameters the concept nondimensionalization of permeability is described different internal junctions
The osmotic effect of the material of structure；The external structure size of bar-shaped porous media material is simultaneously：Diameter D=10mm, length l=
50mm, a diameter of 50 μm of the through hole that is opened in bar-shaped porous media material axis.
3. according to claim 1 based on microvascular implantation seed magnetic targeted experiment in vitro device is permeated, its feature exists
The material of the permanent magnet (10.1) in external magnetic field module (10) is neodymium iron boron Nd2Fe14B rare earth permanent-magnetic materials, structure is
Column type, magnetic direction radial magnetizing.
4. according to claim 1 or 3 based on permeate microvascular implantation seed magnetic targeted experiment in vitro device, its feature
Be that external magnetic field module (10) is carried in targeting district (8) outside, the fixture in external magnetic field module (10) be by fixed permanent magnet,
The mode of mobile targeting district changes distance between permanent magnet surfaces and targeting district axis, and distance change scope is 0～7cm.
5. according to claim 1 based on microvascular implantation seed magnetic targeted experiment in vitro device is permeated, its feature exists
Be the ferroso-ferric oxide particle of hydrophilic group will to be obtained through surface modification in described seed suspension (6), be well dispersed in
The stable suspension formed in deionized water；The mean diameter of seed is 20nm, and adds sodium lauryl sulphate SDS wherein
As activating agent, and ensure that the concentration of SDS is 50mM, finally with the glycerol that volume ratio is 5% as viscosity additive.
6. according to claim 1 based on microvascular implantation seed magnetic targeted experiment in vitro device is permeated, its feature exists
Be the ferroso-ferric oxide particle of hydrophilic group will to be obtained through surface modification in described magnetic drug-carrying particle suspension (7), fill
The stable suspension that dispersion is formed in deionized water；The mean diameter of magnetic drug-carrying particle between 50～400nm, and
Sodium lauryl sulphate SDS is wherein added as activating agent, and ensures that the concentration of SDS is 50mM, be finally 5% with volume ratio
Glycerol is used as viscosity additive.
7. according to claim 1 based on microvascular implantation seed magnetic targeted experiment in vitro device is permeated, its feature exists
In cleanout fluid, the concentration of sodium lauryl sulphate is 50mM, and the volume ratio of glycerol is 5%.
8. a kind of as claimed in claim 1 based on the experiment side for permeating microvascular implantation seed magnetic targeted experiment in vitro device
Method, it is characterised in that ill vitro test method is comprised the steps of：
1) configuration concentration be 200mg/L, the seed suspension (7) of 400mg/L, 600mg/L, 800mg/L, 1000mg/L；
2) configuration concentration is respectively 200mg/L, and 400mg/L, 600mg/L, 800mg/L, 1000mg/L magnetic drug-carrying particle is suspended
Liquid (6), magnetic drug-carrying particle mean radiuss be 50nm, 150nm, 250nm, 350nm, 400nm；
3) cleanout fluid is configured；
4) quality of dry collection ware (5) is weighed, cylindrical permanent magnet surface and bar-shaped porous media material (9) axis is set
The distance between be 1cm-5cm；
5) the bar-shaped porous media material (9) that permeability parameters are 1 is soaked completely with cleanout fluid；
6) whole experiment in vitro device is connected, the cleanout fluid for extracting certain volume with the second syringe (3), and it is injected into reality
In the fluid passage of experiment device until end has liquid to flow out；
7) constant flow rate for arranging dual pathways syringe pump (1) makes liquid flow in targeting district bar-shaped hole dielectric material (9) intermediate throughholes
Speed is 20mm/s, extracts magnetic seeds suspension (7) 10mL and on the lower channel of syringe pump with the second syringe (3),
Connect glass tubing (4)；Concentration is extracted with the first syringe (2) to be 200mg/L magnetic drug-carrying particle suspension (6) 20mL and pacify
It is mounted on the upper channel of syringe pump, connects glass tubing (4)；
8) start syringe pump lower channel, start to inject seed suspension up to terminating, from the kind fullness over the chest during pregnancy that whole experimental provision flows out
Turbid liquid is collected with beaker；Syringe pump upper channel is again started up, starts to inject magnetic drug-carrying particle suspension, from whole experimental provision
The magnetic drug-carrying particle suspension of outflow is collected with the collection ware (5) for weighing quality；
9) the cleanout fluid injection experimentses device of certain volume is extracted with the second syringe (3) again, until liquid is from experimental provision
Flow out end；
10) liquid portion that will be collected in the magnetic drug-carrying particle suspension that collects in ware (5) is dried, and is weighed wherein at large
The quality of the magnetic drug-carrying particle for obtaining；
11) capture rate is calculated：The mass M of the magnetic drug-carrying particle of injection experimentses device is calculated according to concentration known with volumei, press
Collect the mass M of collection Mass Calculation of the ware before and after experiment magnetic drug-carrying particle at large as beforeo, calculate capture rate
12) said process three times is repeatedly performed with identical experiment parameter, seeks CE meansigma methodss；
13) repeat said process under other experiment parameters successively, until the experiment of all parameters is fully completed.
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