CN104458504A - Diffusion cell membrane module and diffusion cell - Google Patents
Diffusion cell membrane module and diffusion cell Download PDFInfo
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- CN104458504A CN104458504A CN201310422389.4A CN201310422389A CN104458504A CN 104458504 A CN104458504 A CN 104458504A CN 201310422389 A CN201310422389 A CN 201310422389A CN 104458504 A CN104458504 A CN 104458504A
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Abstract
The present invention relates to a diffusion cell membrane module, which provides at least a separate barrier compartment for various forms of conventional diffusion cells and is used for simulating the diffusion process that a substance passes through a monolayer or multi-layer semi-solid or non-solid barrier. The membrane module comprises an outer wall, filtration membranes, volume metering rings and an enhanced network, wherein at least the one barrier compartment is enclosed through the alternating and repeated alignment of the filtration membranes and the volume metering rings so as to separate the donor chamber and the acceptor chamber of the diffusion cell and allow the substance to diffuse and pass through.
Description
Technical field
Diffusion cell is made up of donor compartment, receptor compartment, barrier stationary installation, holdout device and sampling and pick-up unit usually; can be used for simulation substance (molecule, ion, particle or drop etc.) through the diffusion process of various barrier, be applied to and spread in relevant experimental study.Membrane module involved in the present invention is the one in the barrier stationary installation in diffusion cell system.
Background technology
Diffusion cell is used widely in research fields such as medical science, catalytic science, environmental science and geological sciences at present, therefore also create various dissimilar diffusion cell to meet different research needs, such as, in diffusion process, the membranes barriers in drug screening can be used for the diffusion cell of barrier oxygen supply, the research etc. of the diffusion cell of film both sides electrochemical properties for catalyzer can be monitored in diffusion process.Existing multiple commercial diffusion cell instrument comes out at present, and comprise the thermostat containing multiple diffusion cell and even a whole set of full-automatic sampling analytical system, wherein most widely used is the dissimilar diffusion cell that permegear company of the U.S. produces.
But the patented technology of these diffusion cells is mainly at sampling mode, the maintenance mode of monitoring mode diffusion cell external environment condition and the maintenance mode of diffusion barrier surrounding environment are innovated, but essential distinction (all being clipped by the Flange Plane of two frosteds) is not had in barrier stationary installation, therefore can only be applied in the research of the solid-state diffusion barrier with some strength itself, such as skin, gastrointestinal tract mucous, petrographic thin section, catalyst support etc., be not suitable for some non-solid diffusion barrier, such as rete malpighii (being distributed in the mucus shape liquid film outside tissue adherence), blood, face cream, semisolid culturemedium, cell monolayer, mud etc. in treatment tank, because this special dispersive medium cannot clip between the flanges form complete barrier.
Thus conventional diffusion cell cannot meet the needs that some are in particular cases studied, such as in the research of oral Pharmaceutical dosage forms, need to simulate novel form enters blood process through intestines wall, intestines wall is made up of multilayer structure, wherein to its main inhibition of drug diffusion is rete malpighii and epithelium layer, rete malpighii is by mucoitin (glycoprotein), lipid, inorganic salts, cell fragment, the thick semi solid that the compositions such as immunoglobulin (Ig) are formed or fluent meterial, adhere to inside intestines wall and in enteric cavity, constantly secrete renewal by intestinal epithelial cell, play lubrication and prevent external source objectionable impurities (toxin, bacterium, virus etc.) effect of invading.Conventional diffusion cell cannot be applied in above-mentioned research, specifically see embodiment 1, and comprise the diffusion cell of membrane module of the present invention, rete malpighii can be placed in independently shielded cubicle, medicine is allowed to diffuse into barrier cell from donor compartment, through rete malpighii, finally enter receptor compartment, research kinetics of diffusion process.
Summary of the invention
The present invention relates to a kind of diffusion cell membrane module, its advantage is to be arranged between the donor compartment of diffusion cell and receptor compartment by non-solid barrier material, and described non-solid barrier comprises the materials such as blood plasma, cell, mucus, nutrient culture media, face cream and mud.Described membrane module can be applied to commercial Franz diffusion cell or horizontal proliferation pond, does not need the structure and the element that change original diffusion cell, also can be applied in the diffusion cell of designed, designed.The diffusion cell being provided with described membrane module can be simulated with detection material through diffusion process during non-solid barrier.
The Basic Design thinking of membrane module involved in the present invention utilizes suitable filter membrane to be separated by the sample in non-solid barrier and donor compartment and receptor compartment.Described filter membrane allows research object to enter receptor compartment from donor compartment through membrane module, prevent the non-solid barrier of membrane module inside from entering donor compartment or receptor compartment simultaneously, and avoid the disturbance that causes due to stir and sampling etc. in donor compartment and receptor compartment to the impact of non-solid barrier.
Described new membrane assembly is formed primarily of two parts, the separable outer wall with support and sealing function of the first one, its two multilayer (or individual layer) barrier cell structure formed by having the segmentation of certain thickness constant volume circle pad between multilayer filter membrane and filter membrane.
Described cell structure is for holding the non-solid barrier of needs research.The volume of non-solid barrier and thickness are determined by the internal diameter of constant volume circle and thickness.For selected filter membrane, can arrange outside the filter membrane of multilayer cell or enhancing net is not set, in order to limit the volume of barrier cell, preventing soft filter membrane from expanding to side.
Described cell structure can be contained in inside and compress by described shell mechanism, and before and after only exposing, effective contact area of both sides, is connected with donor compartment and receptor compartment respectively, needs the diffusate of research to be arranged in donor compartment.
Once applying in the model experiment that the present invention carries out, first diffusate in donor compartment passes the ground floor filter membrane near donor compartment after entering membrane module through connecting hole, enter first barrier cell, then through barrier, and then enter next barrier cell, until finally enter receptor compartment through second layer filter membrane.In this course can manually or automatic sampling detect the concentration of diffusate in donor compartment and receptor compartment, then draw kinetics of diffusion curve; Original position replacing and sampling can also be carried out to the non-solid barrier in every one deck cell by the through hole connecting extraneous and barrier cell.
Accompanying drawing explanation
The structural representation of Fig. 1---conventional vertical diffusion cell (Franz diffusion cell);
Fig. 2---the structural representation of described diffusion cell;
Fig. 3---the profile schematic diagram of donor compartment and receptor compartment in described diffusion cell;
Profile schematic diagram after Fig. 4---membrane module decomposes;
Fig. 5---in membrane module, outer wall A is from the vertical view of film cavity side;
In Fig. 6---embodiment 1, receptor compartment drug concentration and medicine are across rete malpighii rate of diffusion curve
In Fig. 7---embodiment 3, receptor compartment drug concentration and medicine are across rete malpighii rate of diffusion curve
In Fig. 8---embodiment 4, receptor compartment drug concentration and medicine are across rete malpighii rate of diffusion curve
In Fig. 9---embodiment 5, receptor compartment drug concentration and medicine are across blood plasma rate of diffusion curve
Figure 10---constant volume circle and outer wall A assemble schematic diagram and sample passage A and the B location drawing
Explanation numbered by table 1.
| Numbering | Explanation | Numbering | Explanation | Numbering | Explanation |
| 1 | Donor compartment | 2 | Receptor compartment | 3 | Membrane module |
| 4 | Barrier cell | 5 | O type circle | 6 | Sampling lid |
| 7 | Thief hole | 8 | Bolt | 9 | Stirrer |
| 10 | Membrane module connecting hole | 11 | Fixing eaves | 12 | Screw |
| 13 | Outer wall A | 14 | Outer wall B | 15 | Donor compartment connecting hole |
| 16 | Film cavity | 17 | Receptor compartment connecting hole | 18 | Strengthen net |
| 19 | Filter membrane | 20 | Constant volume circle |
Embodiment
Embodiment 1:
Understand for ease of contrasting, the model first adopting Tianjin Zheng Tong company to produce is that the drug transdermal diffusion instrument mensuration medicine of ff-18 passes the rate of diffusion of slime layer in contrast, and wherein diffusion cell type is franz vertical diffusion pond, and its structure can with reference to accompanying drawing 1.
Because the mobility of rete malpighii own is strong, cannot be clamped between upper and lower flange face, having to first to introduce one deck filter membrane is fixed between flange, then being extracted by certain volume spreads on filter membrane from the rete malpighii of pig stomach, then fill damping fluid in receptor compartment, Franz diffusion batteries is installed and inserts constant temperature water bath.
Add finite concentration fluorescein aqueous solution in donor compartment, fluorescein is a kind of Small molecular that can send intense green fluorescence under 485nm illumination is penetrated, herein for simulating the diffusate through rete malpighii.
Diffusate starts timing after adding donor compartment immediately, and timing sampling and measuring fluorescein content from receptor compartment, kinetics of diffusion curve is done to the time, the results are shown in accompanying drawing 6.
As can be seen from the figure, kinetics of diffusion curve serious distortion, major embodiment is penetrability diffusion, big ups and downs and poor repeatability.Cause the reason of this phenomenon to be that barrier material is not separated with donor compartment, inevitably cause barrier material artificially to be diluted and erosion damage during application of sample, thus make poor repeatability between result, be difficult to reflect the truth of sample through rete malpighii diffusion.
Embodiment 2:
The membrane module (3) with an independent barrier cell designed according to this invention, its structure can with reference to accompanying drawing 4 and accompanying drawing 5, the diffusion cell material can simulated in people's coelenteron being provided with this membrane module passes intestines wall surface rete malpighii close to enterocyte, or the diffusion process contrary with it.It is characterized in that described membrane module is by outer wall A(13), outer wall B(14), filter membrane (19), constant volume circle (20) and strengthen net (18) form.
Described outer wall A(13) be the square plate structure be made up of teflon, length of side 50mm, thickness 5mm, its side is provided with circular groove, is provided with manhole in the middle part of groove, groove diameter 35mm, depth of groove 3mm, through-hole diameter 15mm; 8 through holes are provided with, diameter 3mm in the middle part of outer wall corner and surrounding.
Described outer wall B(14) be the ring plate structure be made up of teflon, thickness 3mm, is provided with through hole in the middle part of it, through-hole diameter 15mm,
Oppose side wall has carried out the better gluing, sealing of groove that graining process makes on itself and outer wall A.
Described individual layer barrier cell (4) is arranged in order is formed by enhancing net 1, filter membrane 1, constant volume circle, filter membrane 2, enhancing net 2.
Described enhancing net (18) to be a thickness the be 40 order copper mesh of 50 μm.
Described constant volume circle (20) is a silica gel annular gasket, thickness 0.5mm, and hollow cavity cross-sectional diameter is 15mm.
Described filter membrane (19) is the porose filter membrane of water system of a polyethersulfone, thickness 20 ± 2 μm, 0.8 μm, aperture.
The example of the number of assembling steps of application membrane module (3) is:
1. by one strengthen net (18) put into outer wall A(13) on groove;
2. a slice filter membrane (19) is put into outer wall A(13) on groove;
3. a constant volume circle is put into outer wall A(13) on groove;
4. insert barrier cell by pipettor accurate measuring 100 μ l mucus;
5. successively second filter membrane and second are strengthened net carefully and put into outer wall A(13) on groove;
6. outer wall B is pressed into outer wall A(13) on groove and fasten;
Embodiment 3:
Designed according to this invention is provided with the diffusion cell with independent barrier cell membrane module, and its structure can with reference to accompanying drawing 2 and accompanying drawing 3; It is characterized in that the membrane module (3) of described diffusion cell designed by donor compartment (1), receptor compartment (2) and embodiment 2 forms.
Described donor compartment (1) with reference to accompanying drawing 3, can be made by polymethylmethacrylate with the structure of receptor compartment (2).Fixing eaves arranges 8 through holes corresponding with lead to the hole site on outer wall A, aperture 3mm.By bolt, donor compartment, membrane module and receptor compartment are fixed and clamped, O type circle are set therebetween and prevent from revealing.
Apply described diffusion cell to measure fluorescein and through the example of rete malpighii kinetics of diffusion curve method be:
1, the diffusion cell assembled be placed in 37 DEG C of water-baths and stir;
2,50ml fluorescein aqueous solution is added donor compartment;
3,50ml water is added receptor compartment;
4, measure receptor compartment fluorescein concentration every 30min;
5, fluorescein concentration was mapped to the time;
6, fluorescein rate of diffusion (diffusing through the fluorescein total amount of unit area rete malpighii in the unit interval) was mapped to the time;
Gained kinetics of diffusion curve is shown in accompanying drawing 7.
Embodiment 4:
Use the membrane module designed by embodiment 2 and assembling mode, just change constant volume circle, new constant volume circle thickness is 1mm, and after changing, in the present embodiment, the barrier cell thickness of membrane module becomes 1mm; In assembling mode, the volume that adds of the 4th step mucus becomes 200 μ l from 100 μ l.Be applied to by above-mentioned membrane module in diffusion cell designed by embodiment 2 and diffusion experiment method, the kinetics of diffusion curve finally obtained is shown in accompanying drawing 8.
Embodiment 5:
Use the membrane module designed by embodiment 2 and assembling mode, just in assembling mode, the isopyknic fresh plasma of the 4th step replaces mucus, adds anti-coagulants in blood plasma; Be applied to by above-mentioned membrane module in diffusion cell designed by embodiment 2 and diffusion experiment method, the kinetics of diffusion curve finally obtained is shown in accompanying drawing 9.
Embodiment 6:
The membrane module with two independent barrier cells designed according to this invention, the material that the diffusion cell being provided with this membrane module can be simulated in sewage settling tank enters at the bottom of pond through top layer mud and deep layer mud successively, or the diffusion process contrary with it.Its structure can with reference to accompanying drawing 4 and accompanying drawing 5.It is characterized in that described membrane module is by outer wall A(13), outer wall B(14), filter membrane (19), constant volume circle (20) and strengthen net (18) form.
Described outer wall A(13) be the rectangular flat structure be made up of stainless steel steel, length 15cm, width 10cm, thickness 20mm.Its side is provided with square indentations, groove cross section length of side 8cm, degree of depth 17mm; Be provided with manhole in the middle part of groove, its diameter is 6cm; 8 through holes are provided with, diameter 6mm in the middle part of outer wall corner and surrounding.
Described outer wall B(14) be the square plate structure be made up of stainless steel, thickness 13mm; Manhole is provided with, through-hole diameter 6cm in the middle part of it; Oppose side wall has carried out the better gluing, sealing of recess sidewall that graining process makes on itself and outer wall A;
Described barrier cell (4) is two independently disc-shaped cavitys, is arranged in order is surrounded by enhancing net 1, filter membrane 1, constant volume circle 1, filter membrane 2, enhancing net 2, constant volume circle 2, filter membrane 3, enhancing net 3.
The corrosion resistant plate of described enhancing net (18) to be a thickness be 0.2mm, above has evenly distributed circular hole, aperture 3mm, porosity 50%.
Described constant volume circle (20) is a teflon square plate, length of side 8cm, thickness 2mm, and middle part is provided with manhole, and its diameter is 6cm; Through hole is provided with as sampling passage A on its annular hollow place sidewall, along the radial direction being parallel to schistose surface; Corresponding to the sampling passage A on constant volume circle, on the sidewall of the groove of outer wall A, along being parallel to outer wall A(13) surface radial direction be provided with through hole as sampling channel B; Described sampling channel B is connected with sampling passage A, and its structure can with reference to accompanying drawing 10.
Described filter membrane (19) is a synthetic fabrics, aperture 200 order, thickness 200 μm.
The example of the number of assembling steps of application membrane module (3) is:
1. by one strengthen net (18) put into outer wall A(13) on groove;
2. a filter membrane (19) is put into outer wall A(13) on groove;
3. a constant volume circle is put into outer wall A(13) on groove, note direction, sampling passage A is connected with sampling channel B;
4. by same procedure successively by filter membrane 2, strengthen net 2, constant volume circle 2, filter membrane 3 and strengthen net 3 put into outer wall A(13) on groove;
5. by outer wall B(14) be pressed into outer wall A(13) on groove and fasten;
6., by corresponding sampling passage, top layer mud sample and deep layer mud sample are joined successively two independently in barrier cell.
Above-mentioned exemplary embodiments of the present invention all in be exemplary, instead of it is determinate, therefore the present invention can carry out the multiple modification of exemplary embodiments per sample with applied environment, technician can obtain described modification from the description comprised, and all these modification are considered to fall in scope and spirit of the present invention.
Claims (10)
1. a diffusion cell membrane module, is characterized in that: membrane module (3) comprises outer wall A(13), outer wall B(14), strengthen net (18), filter membrane (19) and constant volume circle (20);
Outer wall A(13) be a plate-like structure, the side surface in flat board is provided with groove, is provided with through hole in the middle part of groove;
Outer wall B(14) be a plate-like structure, be provided with through hole in the middle part of flat board, be parallel to outer wall B(14) the outer wall B(14 on surface) cross section be parallel to outer wall A(13) section shape and size of surperficial groove is identical;
Constant volume circle (20) is the plate-like structure being provided with through hole in the middle part of in the of;
Outer wall B(14) one end or all embed in groove;
In groove, from outer wall B(14) to outer wall A(13) direction be provided with filter membrane (19), constant volume circle (20), filter membrane (19) successively; Or in groove, from outer wall B(14) to outer wall A(13) direction be provided with filter membrane (19) successively, by filter membrane (19) constant volume circle (20), the filter membrane (19) of more than two or two separately;
Be provided with in the side of filter membrane (19) and strengthen net (18), filter membrane (19) amplexiforms mutually with enhancing net (18).
2. membrane module according to claim 1, is characterized in that: in constant volume circle (20) through hole, become at least one independently barrier cell (4) by filter membrane with constant volume corral.
3. membrane module according to claim 1, it is characterized in that: described outer wall A(13) be made up of at least one in glass, quartz, polymethylmethacrylate, teflon and Steel material, thickness, between 1mm to 100mm, is parallel to outer wall A(13) the outer wall A(13 on surface) the outline area in cross section is between 1cm
2to 1000cm
2between; Groove is set in the side of outer wall A as film cavity (16), is parallel to the area of section of outer wall A surface groove between 0.5cm
2to 800cm
2between, its degree of depth is between 1mm to 100mm; Portion arranges manhole as donor compartment connecting hole (15) in a groove, and its diameter is between 0.2cm to 20cm;
The sidewall of described film cavity is through frosted process or arrange fluid sealant, packing washer or arrange internal thread, is convenient to be connected with outer wall B, prevents barrier material from revealing.
4. membrane module according to claim 1, it is characterized in that: described outer wall B(14) be made up of at least one in glass, quartz, polymethylmethacrylate, teflon and Steel material, thickness is between 1mm to 100mm, can embed in the film cavity on outer wall A, it is arranged manhole as receptor compartment connecting hole (17), its diameter is between 0.2cm to 20cm.
5. membrane module according to claim 1, it is characterized in that: described filter membrane (19) is one or two or more kinds in microfiltration membranes, NF membrane, ultra filtration membrane, reverse osmosis membrane, forward osmosis membrane, electric osmose film, concrete, described filter membrane material is made up of at least one in teflon, cellulose mixture, polyethersulfone, nylon, polycarbonate, polyester, polyacrylonitrile, polyimide, polyamide, pottery, micropore glass, stainless steel and carbon materials, its aperture is between 0.001 μm to 50 μm, and thickness is between 10 μm to 5000 μm; Can not wrap in the side of film or two side surfaces by or wrap the collagen layer being convenient to cell tactophily.
6. membrane module according to claim 1, it is characterized in that: described enhancing net (18) is made up of at least one in glass fibre, copper, steel or synthetic fabrics material, mesh is between 500 order to 5 orders, and its thickness is between 50 μm to 2000 μm.
7. membrane module according to claim 1, is characterized in that: described constant volume circle (20) is made up of at least one in silica gel, stainless steel, teflon, synthetic resin, quartz, silicon chip, metal material; Described constant volume circle is annular slice, and its thickness is between 0.05mm to 80mm, and xsect external diameter is between 0.3cm to 25cm; Through hole is provided with as sampling passage A in the inner on portion's annular hollow place sidewall, along the radial direction being parallel to schistose surface; Corresponding to the sampling passage A on constant volume circle, on the sidewall of the groove of outer wall A, along being parallel to outer wall A(13) surface radial direction be provided with through hole as sampling channel B; Described sampling channel B is connected, for carrying out original position replacing and sampling to the material in barrier cell with sampling passage A.
8. membrane module according to claim 1, it is characterized in that: outer wall B(14) one end or all embed be placed with filter membrane (19), strengthen in the groove of net (18) and constant volume circle (20), outer wall B(14) surrounding side wall surface and outer wall A groove madial wall between fit tightly.
9. membrane module according to claim 1, is characterized in that: the barrier material added in barrier cell (4), and barrier material can be one or two or more kinds mixing in blood plasma, cell, mucus, nutrient culture media, face cream and mud.
10. a diffusion cell, is characterized in that: described diffusion cell comprises donor compartment, receptor compartment, the arbitrary described membrane module of claim 1-9; Be connected by interface channel between donor compartment and receptor compartment, on interface channel, establish membrane module, by membrane module, donor compartment and receptor compartment are separated.
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| CN201310422389.4A CN104458504A (en) | 2013-09-16 | 2013-09-16 | Diffusion cell membrane module and diffusion cell |
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| CN201310422389.4A CN104458504A (en) | 2013-09-16 | 2013-09-16 | Diffusion cell membrane module and diffusion cell |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107462507A (en) * | 2017-08-11 | 2017-12-12 | 上海交通大学医学院附属第九人民医院 | A kind of porous material drainage rate determining instrument |
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