CN101301632B - Chemical reaction kit, production method thereof and chemical reaction kit driving system - Google Patents

Abstract

The invention enables to provide a chemical reaction box. The chemical reaction box realizes predetermined regulation easily without generating difference among operators. The chemical reaction box is sealed and one-off and has safety structure to virus and dangerous medicaments. The box of the invention is used to carry out chemical reaction of samples, comprising a container formed by a rigid substrate and an elastomer, wherein the container is provided with two or more chambers that are communicated or arranged to be communicated by a fluid passage and closes the fluid passage or chambers or both partly by applying external forces of the container so as to move or block the fluid materials in the fluid passage or chamber.

Description

Cartridge for chemical reaction, its manufacture method and chemical reaction box driving system

The application be that November 10, application number in 2004 are 200410090633.2 the applying date, denomination of invention divides an application for the Chinese patent application of " cartridge for chemical reaction, its manufacture method and chemical reaction box driving system ".

Invention field

The present invention relates to cartridge for chemical reaction, more specifically, relate to a kind of like this cartridge for chemical reaction, wherein synthetic, the dissolving of solution, detection, separation or similar operation, rules according to appointment can easily be carried out under low cost, and can not produce the error between the operator.

Background technology

Traditionally, test tube, beaker, pipette or similar instrument generally have been used to handle synthetic, dissolving, detection, separation or similar operation such as solution.For example, as shown in Figure 1, substance A and substance B are collected in container 1 and container 2 respectively for example in test tube or the beaker.Then, pour these materials into container 3, for example in test tube or the beaker, these materials are mixed or stir and generate substance C.In this manner synthetic of substance C for example, can be observed by luminous, heating, variable color, color contrast or similar phenomenon.

In addition, compounding substances is carried out diafiltration, centrifugation or similar operation, separate and extract target substance.

And, use glass apparatus, as test tube or beaker, carry out the processing such as dissolving, for example, with an organic solvent dissolve.And, in testing process, as shown in Figure 1, the reagent that is tried in substance A and the container 2 in the container 1 is injected container 3, observe their reaction result.

On the other hand, for the device of biological analyser and so on, for example, use the flat bag of making by flexible material, described in Japanese unexamined patent No.2002-365299.

Fig. 2 is the structure chart of the biochip described in the above-mentioned Japanese unexamined patent No.2002-365299.Fig. 2 (a) is a cutaway view, and Fig. 2 (b) is a plane.The core of the flat blood collection bag 41 that seals at the edge is bags of fish shape.The opening of fish shape bag seals with rubber stopper 42.

In blood collection bag 41, according to forming collecting bag 43, pretreating zone 44, junction surface 45 and waste reservoir 47 from filling in 42 orders to the rear portion.Collect in order to carry out blood, plug 42 inserts in the syringe (not shown), and wherein the syringe needle of syringe passes plug 42.

Collect in order to carry out blood, plug 42 inserts in the syringe (not shown), and wherein the syringe needle of syringe passes plug 42.

Collect in order to carry out blood, the needle point of stretching at the syringe needle of syringe exterior inserts in examined people's the health.The hook 52 of blood collection bag 41 is drawn out, and makes blood be collected in collecting region 43.Blood is extracted syringe out after collecting from blood collection bag 41.Then, as shown in Figure 3, blood collection bag 41 is clipped between the rotation roller 61 and 62, with biochip 44 extruding from collecting region 43 towards pretreating zone, the blood of collecting is delivered to pretreating zone 44.

When roller 61 and 62 runnings and beginning squeeze bag 48, the solution in the bag 48 is washed valve 49 open, flows into pretreating zone 44.Then, the solution in the bag 50 flows into pretreating zone 44 in the same way.When the assignment procedure in the pretreating zone 44 finished, roller was rotated further, and the blood of handling is delivered to junction surface 45.

DNA chip 46 is arranged in the junction surface 45 hybridizes.Unnecessary blood or the solution handled at pretreating zone 44 are stored in the waste reservoir 47.Utilization is arranged in outside reading device the situation of carrying out the DNA chip 46 of hybridizing is observed.

But, use the conventional method of beaker, pipette or analogous instrument to have some problems, for example, complicated operation, difference is big between the different operating person, and requires a great deal of time and work.

In addition, blood collection bag be problematic in that it is not easy to be used for moving liquid because these the bag lack flexibility.

Summary of the invention

An object of the present invention is to provide manufacture method and a kind of chemical reaction box driving system of a kind of cartridge for chemical reaction, this cartridge for chemical reaction, described cartridge for chemical reaction can easily be finished the operational procedure of appointment and not have difference between the different operating person, this cartridge for chemical reaction be sealing with disposable, and have at the virus and the safeguard construction of dangerous drug.

Brief description of drawings

Fig. 1 represents processing method of the prior art;

Fig. 2 is the structure chart of blood collection bag in the prior art;

Fig. 3 represents the method for operating of blood collection bag;

Fig. 4 is the structure chart of an embodiment of cartridge for chemical reaction of the present invention;

What Fig. 5 showed is mode of operation;

Fig. 6 represents another mode of operation;

Fig. 7 is the structure chart of another embodiment of the present invention;

Fig. 8 represents an embodiment of relevant fluid passage pressure method;

Fig. 9 represents another embodiment of relevant fluid passage pressure method;

Figure 10 represents another embodiment of relevant fluid passage pressure method;

Figure 11 represents the structure chart of another embodiment of the present invention;

Figure 12 represents the method for pressurizeing;

Figure 13 represents a concrete example of fluid passage shape;

Figure 14 represents the method for another pressurization;

Figure 15 represents the method for another pressurization;

Figure 16 represents the method that another pressurizes;

Figure 17 is the structure chart of another embodiment of the present invention;

Figure 18 represents the shape of fluid passage or chamber;

Figure 19 represents to have the elastomer of hierarchy;

Figure 20 represents the detection method of reative cell;

Figure 21 represents the structure chart of another embodiment of box;

Figure 22 represents the structure chart of another embodiment of box;

Figure 23 represents the structure chart of another embodiment of box;

Figure 24 represents the structure chart of embodiment of the inlet of box;

Figure 25 represents the figure relevant with matrix material;

Figure 26 represents with injection and engages relevant method;

Figure 27 is the structure chart of another embodiment of box;

Figure 28 is the structure chart of another embodiment of box;

Figure 29 represents the inhalation method of sample;

Figure 30 is the structure chart of another embodiment of box;

Figure 31 represents an embodiment of the shape of chamber;

Figure 32 has shown processed object;

Figure 33 represents to make an embodiment of cell homogenising;

Figure 34 is the structure chart of another embodiment of box;

Figure 35 is the structure chart of another embodiment of box;

Figure 36 is the structure chart of another embodiment of box;

Figure 37 represent with elastomer and matrix between a relevant embodiment of junction surface;

Figure 38 is the structure chart of another embodiment of box;

Figure 39 is the structure chart of an embodiment of cartridge for chemical reaction of the present invention;

Figure 40 is the structure chart of another embodiment of cartridge for chemical reaction of the present invention;

Figure 41 is the structure chart of another embodiment of cartridge for chemical reaction of the present invention;

Figure 42 represents another embodiment of flow passage pressure method;

Figure 43 represents another embodiment of relevant fluid passage pressure method;

Figure 44 represents to have for a chamber embodiment of 6 fluid passages formation, wherein is formed with three close/open valves;

Figure 45 represents another embodiment of the shape of roller;

Figure 46 represents another embodiment of the shape of roller;

Figure 47 represents to use an embodiment of the roller with projection;

Figure 48 represents the major part of an embodiment of cartridge for chemical reaction of the present invention;

Figure 49 represents the major part of another embodiment of the present invention;

Figure 50 represents the major part of another embodiment of the present invention; And

Figure 51 represents the major part of another embodiment of the present invention.

The specific embodiment mode

At length explain the present invention below with reference to accompanying drawing.Fig. 4 is the structure chart of an embodiment of cartridge for chemical reaction of the present invention.Fig. 4 (a) is a perspective view, the elastomeric bottom view that Fig. 4 (b) is.Fig. 4 (c) is the cutaway view along Z-Z '.Cartridge for chemical reaction 100 comprises by the elastic caoutchouc of sealing or the elastomer 110 made of similar material, and the tabular matrix (rigid body matrix) 120 of being determined the position and being kept shape by hard material being used for of making.

Viscoelastic body or plastic body can be as the elastomers 110 (still, elastomer is used as the example of embodiment) of box.

Shown in Fig. 4 (b), be formed for holding hole (below be called " chamber ") 111 and 112 (they are the cavity recessed from the surface) of solution in the bottom surface of elastomer 110, the chamber that is used to react (being also referred to as " reative cell ") 113, the chamber (being also referred to as " waste reservoir ") 114 that is used to store waste liquid and the fluid passage 115 that is communicated with these chambers.

Shown in Fig. 4 (c), the remainder of the elastomer 110 except the fluid passage and plane bonding zone 116, be bonded on the surface of matrix 120, thereby formation chamber and fluid passage are used to prevent that by the structure of elastomer 110 and matrix 120 sealings solution is leaked to the outside.

Transfer to the solution in the box with this structure makes an explanation below.Material (below be called " solution ", because with solution as an example) A and solution B are infused in the chamber 111 and 112 that forms in the box 100 in advance.Solution utilizes syringe 118 injections after syringe needle 117 directly inserts elastomer 110, shown in Fig. 4 (c).Because elastomer 110 is made by elastomeric material, therefore when syringe needle 117 was extracted out, pin hole was with own closure.For complete closed hole, after injecting solution, to pin hole filling adhesive or similar material.Yet, also can utilize heating for dissolving to come closed hole.

As shown in Figure 5, from the left end of box 100 top to lower compression roller 130 to a certain degree, chamber 111 is flattened.Then, if roller 130 rotation, and 1 move right from the position, shown in Fig. 6 (a), the solution A that is stored in the chamber 111 is extruded to the right.Solution A is transported to reative cell 113 by fluid passage 115.Air in the chamber 113 is sent in the waste reservoir 114.

If roller 130 is rotated further and moves to the position 2 shown in Fig. 6 (b), the solution B in the chamber 112 is sent.Solution B flows into reative cell 113 by fluid passage 115.In this case, when roller 130 when pressing down, the part of fluid passage 115 central roll processes also is crushed, and correspondingly becomes the valve of an anti-backflow, thereby prevents that solution B from flowing back in the chamber 111.

When solution A and solution B entered reative cell 113, they were mixed and react.The reaction here is meant, for example, mixes, synthesizes, dissolves, separates or similar process.

Use these boxes to detect, for example, dioxin, DNA or similar material.

In addition, if roller 130 rotates and after the position 3 shown in Fig. 6 (c) moves to position 6, when roller 130 rotates and move to position 7 shown in Fig. 6 (d) in opposite direction, can easily solution be mixed.

Usually, roller 130 finishes to rotatablely move in a direction (path).

These boxes can be made with little size, light weight and low cost.And, handle rules, as the mixing of material, synthetic, dissolving, separate or detect, can easily in box, carry out, and can between the different operating person, not create a difference.

In addition, box of the present invention be the sealing with disposable.It can handle virus, dangerous drug or similar material safely.For example, can safely and in this box, carry out processing (a series of processing of plant chimney stalk and concentrated waste water reliably, as neutralization, distillation, sampling, mixing and colorimetric estimation), the cyanogen in rivers that waste water flows into or similar place detects, from blood or ill extracting section DNA or protein, perhaps similar process.

Notice these explain it only is to be used to the embodiment that represents that some is suitable, so that illustration the present invention.Therefore, the present invention is not limited to the foregoing description.On the contrary, under the situation that does not depart from spirit of the present invention and inner characteristic, can make much substituting and modification of other.

(1) as shown in Figure 7, not only can form the chamber 111 and 112 that is respectively applied for solution A and B,, also form the chamber 141 and 142 of leading to fluid passage 115 in order to store cleaning fluid or dry air.

(2) as shown in Figure 8, utilize the external force convection cell passage of box outside to pressurize downwards, not only can utilize roller to carry out, and can utilize actuator to carry out, described actuator vertically applies power to syringe 151, chamber 112 wherein shown in Figure 7 or similar structure also can directly be pressurizeed by actuator, thus the solution in can delivery chamber 112.

(3) as shown in Figure 9, can use a plurality of actuators to realize pumping,, just can extrude solution 153 along arrow (to the right) direction if depress wide syringe 152 again after wherein depressing syringe 151.

(4) as shown in figure 10, be arranged in array if having a plurality of actuators of control individual part ability, and to pressing down, they also can be used to have the box of general service fluid passage.

(5) on the surface of the elastomer directly over the fluid passage 110, has projection 161, shown in Figure 11 (a), 11 (b) and 11 (c).Even when the width of fluid passage, shape or number change, they can be crushed and sealing reliably, and wherein rigid matrix 120 helps accurately to keep the position very much.

(6) if the width of roller less than the width of box, shown in Figure 12 (a), the peripheral region of elastomer 110 may be tending towards forming warpage, in this case, shown in Figure 12 (b), utilizes pressurizing frame 171 in advance the peripheral region to be pushed down.

(7) shown in Figure 13 (a), between the chamber of elastomer 110 and fluid passage, form very narrow coupling part, make the easier outflow of solution in described chamber, but, because the factor such as the viscosity resistance does not allow the solution in the fluid passage to enter this chamber.Perhaps, as Figure 13 (b) or (c), can form the film valve and be used for the coupling part.Perhaps, shown in Figure 13 (d), valve can be opened by the pressure of indoor solution, thereby solution is extruded.

(8) as shown in figure 14, can use pressing means 180, its shape is center swell (bending), as a bucket, rather than uses cylindrical roller.Perhaps, as shown in figure 15, can use spherical pressing means 190.Perhaps, as shown in figure 16, can use the pressing means 200 based on suction drawing paper method, it has the circular shape of larger radius of curvature.If pressing means 200 is along right rotation shown in Figure 16, then solution can extrude along the direction of arrow.

(9) shown in Figure 17 (a), if the reative cell 113 of Xing Chenging is the reative cell that approaches at the beginning, it expands along thickness direction when exerting pressure, and does not just need to discharge the air in the reative cell 113.Therefore, in the elastomer 110 of box 100, needn't have the chamber of storing waste liquid.

(10) about the cross sectional shape of fluid passage 115 (or chamber), if the angle is the right angle shown in Figure 18 (a), fluid passage 115 is crushed when then pressurizeing from the top, and shown in Figure 18 (b), and solution is tending towards remaining on the angle.Therefore, shown in Figure 18 (c), the angle should have the curvature that radius is R.If the height of fluid passage 115 is H, width is W, then wish R be H or W 1/10th or bigger.Shown in Figure 18 (d), wish also have the curvature that radius is R, shown in Figure 18 (d) with the joint angle of matrix 120.

(11) wall surface that can convection cell passage 115 carries out surface treatment, if solution dissolves in water, then forms hydrophobic surface; If solution is oiliness, then form hydrophilic surface, be used to prevent the adhesion of solution.Perhaps, can apply Teflon (registration mark) coating, perhaps use the material of Teflon (registration mark) rubber as elastomer 110.

(12) elastomer 110 can have two-layer or multilayer.For example, shown in the schematic diagram (Figure 19 (a) is the bottom view of elastomer 110, and Figure 19 (b) is the cutaway view of elastomer 110) of Figure 19, in ground floor 110a, form chamber 210 and 211, and in second layer 110b, form chamber 220.In addition, form fluid passage 212, be used to connect the chamber 210 of ground floor 110a and the chamber 220 of second layer 110b, thereby make these chambers on three-dimensional, be in compact way.

(13) form reative cell 113, so that can be used for light, voltage, electric current or heat of detection reaction material or the like.For example, whole elastomer can be made (opaque) printing opacity or light tight.Perhaps, only partly make photo measure transparent.If will make opaquely except the part the photo measure part, and then be stored in reactant in these chambers and just can avoid illumination and penetrate.Perhaps, whole elastomer can be formed by insulator, and a part is formed by the elastomer that conducts electricity (containing carbon or similar material).

The light that sends for the observing response material, shown in Figure 20 (a), elastomer 110 is made by transparent material, wherein reads the light that reactive material sends by reading device 230 and observes.Elastomer 110 needs not to be whole clearing.On the contrary, only the photo measure partially transparent is enough.Here, can embed glass chamber or similar structure.

If detect voltage or electric current, if perhaps carry out electrophoresis, shown in Figure 20 (b), conductor 231 and 232 be set, in order to directly to pick up detection signal from reative cell 113.Perhaps, shown in Figure 20 (c), in needs, insert electrode 233 and 234 from the outside.

(14) as shown in figure 21, on elastomer 110, form outlet 235, be used to set up a kind of structure, thereby when utilizing roller 130 pressurization downwards, reactive material is forced into the outside from exporting 235.In this case, hope only is used as the reactive material that is discharged from the material of safety.

(15) as shown in figure 22, can form the lozenges 241 of circular arc on the upper surface of elastomer 110, if wherein tabular increased pressure board 240 pressurizes vertically downward from the top, then solution is discharged along the direction of arrow.

(16) as shown in figure 23, add gland 242 and can utilize hinge 243 to be connected, make to add gland 242 and can freely open or close, thereby can discharge solution when gland 242 is closed adding with matrix 120.

(17) as shown in figure 24, going into interruption-forming negative area 250 for injected sample.When syringe needle 117 inserted or extracts, injection inlet is revealed and sticked to injection.But shown in Figure 24 (b), the injection 251 of leakage can not discharged from box owing to the bottom surface that the viscosity or the surface tension of injection remains in negative area 250.This is useful when injecting fluid (for example blood) itself has harm.Syringe needle 117 extract track 252 auto-closings.

(18) elastomeric manufactured materials can be, for example, and silicon rubber, PDMS (dimethyl silicone polymer), natural rubber and polymer, acrylic rubber, polyurethane rubber or materials similar.These materials need not to be perfect elastomer, can be resin or the plastic bodies with viscoelasticity characteristic, as gel.If material almost is plastically to be out of shape, what under the situation of Figure 18 (b), also being difficult to form the gap.

(19) as the material of matrix 120, can use glass, metal, animi resin, can crooked rigid body or materials similar.Can crooked rigid body if use, shown in Figure 25 (a) and 25 (b), box is placed on hardboard or the desktop 260 exerts pressure, perhaps box 100 is clipped in two rollers, 130 centres from the top with from the below.

(20) for sealing injection arrive chamber 111, chamber 112 or similar structure in injection of solution after enters the mouth, can use heating or adhesive.

Perhaps, shown in Figure 26 (a) and 26 (b), with the end face of elastomer 110 down, chamber then wherein towards last, with injection of solution in the chamber.After this, use matrix 120 to cover the chamber, shown in Figure 26 (b).

(21) combining of elastomer 110 and matrix 120 except utilizing bonding mode, can be utilized absorption (for PDMS, glass or materials similar), ultrasonic wave, heating, plasma treatment, vibration or similar method.

(22) material that is suitable for detecting in box is biomolecule, organic matter, inorganic matter or the organism of living, as bacterium, lesion portion, cell or similar material.

(23), can use magnetic bead, silica beads, silica filter, monolithic (monolith) filter, antibody, enzyme, dendrimer (dendrimer) or similar material as the extraction means for the leaching process in the reative cell.Notice that provide vibration to disperse magnetic bead by vibration source to magnetic bead, for example, described vibration puts on the outside of box.

(24), wish the Hirschfeld-Klinger reaction formal matter is expelled in the waste reservoir earlier for security.

(25) because rigid matrix is fixed on the box, therefore maybe when measuring, can determine accurate position when applying external force.And, shown in Figure 27 (a), can adopt hook or be used for the hole 270 of this hook, be used for when when the outside applies power, fixing a position.Figure 27 (b) is the side view (cutaway view) of box when being fixed on the workbench 271, and wherein align with alignment pin 272 on being installed in workbench 271 in the hole 270 among Figure 27 (a).

In addition, as shown in figure 28, can as measuring telltale mark 273 be set for these are movable.

(26) as shown in figure 29, can use roller 1 30 injected sample.In other words, shown in Figure 29 (a), after inserting syringe needle 117, rotating from injection inlet to the roller 130 that presses down and to move, shown in Figure 29 (b), thereby making (Figure 29 (c)) in the sample suction chamber 111 to the back.

Sample shown in Figure 29 (d), is extracted syringe needle 117 after sucking, and roller 113 upwards lifts and turn back to the home position, and second roller that provides separately perhaps is provided, and the sample that sucks is transmitted towards the back.

If the viscosity of sample is enough big, utilizes the non-return valve effect of roller to transfer sample in the box in the position shown in Figure 29 (d), and do not extract syringe needle 117.

(27) for above-mentioned mixing, projection (or wall) 280 can be set in chamber 113, be used for separating and stirring, as shown in figure 30.

(28) shape of chamber can be the shape such as hexagonal polygon, rhombus, circle or the like, shown in Figure 31 (a), 31 (b) and 31 (c).

(29) box of the present invention not only can Treatment Solution, also can handle biological cell.Shown in figure 32, target cell is placed in the reative cell 113, and will be stored in the pharmaceutical supply in another chamber and offer cell, thereby can cultivate or reaction by observation of cell.

The protein that box of the present invention also is used for cell free system synthesizes.

(30) leg-of-mutton projection 290, its surface has blade, shown in Figure 33 (a), is contained on the matrix 120.Then, shown in Figure 33 (b), roller 1 30 from turning left to the right side, and is reversed again from the right side and to get back to a left side, grind blade with the cell homogenising in the chamber 113 thereby utilize.

(31) the present invention has, for example, and following application:

(a) determine the glucose sensor of concentration of glucose in the blood, wherein box be closed type and can carry out safety test;

(b) measuring N Ox or dioxin;

(c) detect trace element in hair, water or the food, as cadmium, cyanide, arsenide and mercury, wherein box be closed type and can use the method such as colorimetric method to detect agricultural chemicals, noxious material or similar material safely;

(d) use hybridizing method detection or discriminating biopolymer,, perhaps use antigen-antibody reaction to detect or discriminating protein as DNA or RNA;

(e) in testing process, use electrophoresis method to detect or differentiate DNA, RNA or protein;

(f) the chromatography detection molecules of use such as HPLC;

(g) based on the spectroscopy detection molecules of using ultraviolet light, visible light or similar light;

(h) use the chemical reaction or the variation of electrochemical measuring method measurement of species, that is, use such as the electrochemical measuring method of the impedance method chemical reaction of detection material qualitatively or quantitatively, as oxidation-reduction reaction, the perhaps variation of conductance; And

(i) use flow site meter method, utilize fluorescence etc. by identification of cell, as lymphocyte, detection or isolated cell, blood platelet or similar composition;

(32) for the pcr amplification (PCR) of gene, metal 300 is embedded in the matrix 120, as shown in figure 34, wherein the temperature of metal 300 raises or reduces by 310 controls of Peltier heater, thereby is convenient to heat exchange and simplifies pcr amplification.

(33) as shown in figure 35, with little pressing mechanism 320, imbed in the box 100 as rigid body, PZT, memory shape metal alloy, actuator or similar device, wherein pressing mechanism 320 is driven and is subjected to the external pressure of actuator 321 or similar device, and actuator 321 or similar device are exerted pressure downwards and partly closed the fluid passage.

(34), can use the fiber waveguide 330 that is embedded in the box 100, as shown in figure 36 for the reactive material of using up in the detection reaction chamber 113.

(35) shape of the material of original elastomer or box can be used processing technology manufacturing, is shaped and wet or dry ecthing as milling, light.The manufacturing of these chambers not only can utilize lamella shown in Figure 4 bonding, and can general injection be shaped.The mould of injection moulding is to use such as milling, light and is shaped or etching method makes.

(36) sealing of elastomer 110 and matrix 120 not only can be by bonding, and can pass through strain or fit structure.In fit structure shown in Figure 37, on the bonding land end face between elastomer 110 and the matrix 120, form the complementary teeth 341 and 342 of right angled triangle, shown in Figure 37 (a).These teeth mesh together, shown in Figure 37 (b).Note, these teeth in the fluid passage or the entire circumference of chamber zone form.

The feature of this engagement is that when elastomer 110 was pressed downward, elastomer 110 was difficult to horizontal expansion.If along the chamber or the fluid passage projection is set, shown in Figure 37 (c), closed chamber or fluid passage simply.

In addition, being used for part and closing fluid passage or chamber and applied external force mobile or that block the flowing material of fluid passage or chamber, not only can be mechanical force, also can be air pressure.

And as shown in figure 38, can form wedge-like portion 350 in a position (inlet) of box, it at first contacts cylindrical roll.If wedge-like portion 350 is set, make roller 130 only along a direction, promptly to the right direction moves among Figure 38 (a) and 38 (b), and just being enough to just, solution moves to the right side.Do not have wedge shape inlet as compartmentalized box for holding assorted fruits and candies, roller 130 need move along both direction, i.e. downward direction and to right, shown in Figure 38 (c), 38 (d) and 38 (e).

Figure 39 represents an alternative embodiment of the invention.Figure 39 (a) is a plane, and Figure 39 (b) is the partial sectional view of chamber (A, B, C, D, E and G) and projection (dash area of Figure 39 (a)), and Figure 39 (c) is a Z-Z ' cutaway view.In order to simplify, the chamber of solution A is called chamber A, and the chamber of solution B is called chamber B (below identical principle being applied to C, E and G).

Notice that the situation of embodiment as indicated above is the same, cartridge for chemical reaction 100 is to be formed by elastomer 110 (as sealing and flexible rubber) and panel-shaped base body 120 (being made by rigid material).Connection between the material of matrix 120 and elastomer 110 and the matrix 120, also the situation with the foregoing description is identical.

The chamber A that is used to adorn solution is to F, and each all is the cavity recessed towards the surface, is to form in the bottom surface of elastomer 110, shown in Figure 39 (b).Projection 161 is (this projection is a shade in Figure 39 (a)) that form on the top of the chamber recessed towards the surface (A, B, C, E and G) part.

Blood is expelled among the A of chamber, and the solution reagent that will be used for lysed blood is expelled to chamber B, and the magnetic bead that will be used for catching such as the biopolymer of DNA is expelled to chamber C.Chamber D is a reative cell, has wherein applied magnetic field (not shown).Cleaning fluid is expelled among the E of chamber, and buffering liquid is expelled among the G of chamber.Chamber H is the finished product chamber, contains the liquid that reacts in reative cell D.Chamber F is a waste reservoir.

In these chambers, form fluid passage 115, be used to be communicated with them.Chamber A and B form zone (below be called " protrude district ") at projection and form, and are connected to chamber C by fluid passage 115a and 115b, and chamber C also is formed on and protrudes the district.Chamber C is connected to chamber D by fluid passage 115c, and chamber D is the zone that do not have projection (below be called " negative area ").In addition, protruding chamber E and the G that the district forms, be connected to chamber D by fluid passage 115d and 115e.And the chamber H that forms at negative area is connected to chamber D by the fluid passage 115f that forms in the protrusion district.The chamber F that forms at negative area is connected to chamber D by the fluid passage 115g that forms in the protrusion district.

Each chamber of elastomer 110 and the flat except that the fluid passage are bonded on the surface of matrix 120, shown in Figure 39 (c), thereby make these chambers and fluid passage by elastomer 110 and matrix 120 sealings, form one thus and prevent that solution is leaked to outside structure.

Hereinafter, with the solution transfer operation of explaining in the said structure box.

As mentioned above, blood, solution reagent, cleaning fluid and buffering liquid are expelled to respectively among chamber A, B, E and the G that forms in box 100 in advance.The magnetic bead that the surface is had positive charge is expelled among the C of chamber in advance.Injection (not shown) is to utilize, and for example, syringe is finished, and the syringe needle of wherein said syringe directly inserts in the elastomer 110.Because elastomer 110 is made by elastomeric material, if syringe needle is extracted, then pin hole is closed voluntarily.After injection of solution, pin hole is filled with adhesive or similar substance, the hole is sealed fully, but pin hole also can utilize heating for dissolving to seal.

In said structure, shown in Figure 39 (d), roller 130 the left end of box 100 from above be pressed downwardly onto to a certain degree, to protrude the district flattens, if roller 130 rotates and 1 move to position 2 along dextrad from the position, shown in Figure 39 (a), the blood and the reagent solution that then are injected in advance respectively among chamber A and the B are extruded to the right.

As a result, the blood that is expelled in advance among the A of chamber flows into the chamber C that injection in advance has magnetic bead by fluid passage 115a, and the reagent solution that is expelled to chamber B simultaneously in advance flows into chamber C by fluid passage 115b, and blood and reagent solution mix herein.DNA in the blood is trapped on the magnetic bead surfaces among the C of chamber.

Then, roller 130 rotates and 2 moves to position 3 from the position, makes the blood, reagent solution and the magnetic bead that mix among the C of chamber flow into chamber D by fluid passage 115c.Magnetic field is applied among the D of chamber, magnetic bead is hunted down.

Then, roller 130 rotates and 3 moves to position 4 from the position, thereby fluid passage 115f is flattened, and blocks flowing of inlet chamber H.And roller 130 rotates and 4 moves to position 5 from the position.As a result, be expelled to wash liquid stream among the E of the chamber D that enters the room in advance and clean magnetic bead.This cleaning fluid flows into the chamber F (the fluid passage 115f that leads to chamber H is crushed and closes) of dress waste liquid by fluid passage 115g.

Then, roller 130 rotates and 5 moves to position 6 from the position, makes the buffering liquid that is expelled in advance among the G of chamber by fluid passage 115e inflow chamber D (fluid passage of leading to chamber F is flattened and closed by roller 130).Then, heating clamber D will be discharged by the DNA of magnetic capture.DNA that discharges and buffering liquid flow into chamber H by fluid passage 115f, become final products.

Figure 40 is another embodiment of Figure 39 structure.Be with the difference of Figure 39, replace waste liquid chamber F, the outlet formation circulation of fluid passage 115h at reative cell D flow back among the A of chamber waste liquid.Inflow and the outflow by the fluid passage in these chambers of the motion of roller 130 and injection operated, and be identical with Figure 39.This structure can not increase the internal pressure in chamber or the fluid passage, thereby liquid is shifted reposefully.The space of waste liquid chamber F no longer needs, thereby can reduce the shared space of box.

Figure 41 represents the example of another embodiment, does not wherein form projection shown in Figure 39 in the box.Whole box is flat shape, and the length of its central roll 130 is restricted, and makes in the X-Y scope of roller 130 on box to move.Note, chamber A, B, C, E and G be equipped with respectively with Figure 39 in identical injection, and chamber D and also running in an identical manner of H.

In said structure, roller 130 box 100 left sides from above to pressing down chamber A and B, chamber A and B are crushed, as shown in figure 41, if roller 130 rotates and 1 move to position 2 along dextrad from the position, the blood and the reagent solution that then are expelled in advance respectively among chamber A and the B are extruded to the right.

As a result, the blood that is expelled in advance among the A of chamber flows into chamber C by fluid passage 115a, and the reagent solution that is expelled to chamber B simultaneously in advance flows into the chamber C that injection in advance has magnetic bead by fluid passage 115b, and blood and reagent solution mix herein.

Then, roller 130 rotates and 2 moves to position 3 from the position, makes blood, reagent solution that mixes among the C of chamber and the magnetic bead that is used for capture dna flow into chamber D by fluid passage 115c.Magnetic field is applied among the D of chamber, magnetic bead is caught by magnetic field.

Then, roller 130 rotates and 3 moves to position 4 from the position, thereby fluid passage 115f is flattened, and blocks flowing of inlet chamber H.And roller 130 rotates and 4 moves to position 5 from the position.As a result, be expelled to wash liquid stream among the E of the chamber D that enters the room in advance, be used to clean magnetic bead.This cleaning fluid flows into chamber A (the fluid passage 115f that leads to chamber H is crushed and closes) by circulation of fluid passage 115h.

Then, roller 130 rotates and 5 moves to position 6 from the position, makes the buffering liquid that is expelled in advance among the G of chamber by fluid passage 115e inflow chamber D (fluid passage of leading to circulation canal 115e is crushed and closes).Then, heating clamber D will be discharged by the DNA of magnetic capture.DNA that discharges and buffering liquid flow into chamber H by fluid passage 115f, become final products.

Utilize the downward hydraulic fluid passage of external force of box outside, be not limited to roller.As shown in figure 42, oil, water, air or similar material can be expelled in advance and be used for pressurization among the 115i of fluid passage, thereby utilize actuator (not shown) belling to go out part 161, and most advanced and sophisticated A ' expands, and flattens fluid passage 115.

Figure 43 represents another embodiment to chamber or fluid passage pressing mechanism, matrix 120 comprising chamber or fluid passage, the cross section is for protruding the elastomer 110 of shape, and the rigid body 121 that contains elastomer 110 and this elastomeric projection is stretched out, the three combines, the projection of elastomer 110 is subjected to the compacting of roller, actuator or similar device, and above-mentioned fluid passage or constant pressure is flat.As shown in the figure, rigid body 121 is also as the stop of actuator.

Notice that the quantity of leading to the fluid passage 115 of each chamber is arbitrarily.Form 6 fluid passages among Figure 44, wherein three projections 161 (being used to block the fluid passage) shown in Figure 42 or 43 become the plug valve of opening and closing.

Figure 45 represents to have the roller 130a of groove, and wherein groove 131 is formed on the cylindrical roll 130.The projection that forms on the box or the position of chamber can be made up in many ways.

Figure 46 represents to have the roller 130b of projection, wherein is correspondingly to have projection on cylindrical roll 130.Even box is flat, external force also can partly be applied on the box, as the projection shown in Figure 39 (b).

As shown in figure 47, the zone can be divided into Y1 and Y2, wherein projection (a) and projection (b) are used to exert pressure.In this structure, the roller 130b with projection begins to rotate from left end, and moves to position X2 from position X1, and the liquid that will be arranged in the chamber A in Y1 zone is forced into chamber C, and also liquid is pushed back the chamber B that is positioned at the Y2 zone.

Notice that the box shown in the foregoing description has following problem under special circumstances:

(1) for example, if carry out gene magnification, then need heating or cooling.If the sample that adopts particulate to combine with DNA then can apply vibration to them.But, be difficult to heat or vibration are delivered to the box of being made by thick material, on pipe.

(2) make by thin glass as compartmentalized box for holding assorted fruits and candies, when the inner remaining solution that contains virus of box, when abandoning box, work the mischief.In addition, the box price of glass structure is expensive.

Embodiment hereinafter described can address these problems.Even this cartridge for chemical reaction can be heated or be cooled off apace, also can be to the enough vibrations of this box transmission.In addition, heating, cooling or vibration are also little to the influence of adjacent position.This box is safety and cheap also.

Figure 48 represents the major part of the embodiment relevant with this box.The structure of this box is suitable for the gene magnification of PCR-based method, perhaps is used for the sample that magnetic-particle combines with DNA.Notice that following description only relates to characteristic.Feature except characteristic is identical with the foregoing description, therefore, omits the explanation of these features.

In Figure 48,200a is a movement device, allow to make the elastic membrane 110a of its most advanced and sophisticated contact box, and (for example pass through heating of Peltier (Peltier) element or similar elements or cooling chamber A, reative cell 113 among Fig. 4 (b)) sample in perhaps provides vibration by voice coil loudspeaker voice coil or piezoelectric element.In the following embodiments, this movement device is called outer anchor clamps.Notice that sample is meant DNA, magnetic-particle or similar material and solution.

The formation of elastic membrane 110a partly is local, and is limited in the top of chamber A, and outer anchor clamps 200a is in contact with it.This part elastic membrane 110a is thinner than elastomeric other parts, and its thickness is 1mm or less than 1mm.Best thickness " t " for example, is 0.1 to 1mm.

Hereinafter will explain the operation of this structure.Sample is expelled among the chamber A of box.The internal pressure among the A of rising chamber is blocked in fluid passage in the box or similar structure.Elastic membrane 110a remains on extended state.

Notice that internal pressure is not limited in the part of chamber A, but have family in the box that can raise with the fluid passage in internal pressure.

The tip of outer anchor clamps 200a is depressed, and utilize the internal pressure that raises to stick to the surface of elastic membrane 110a.According to handling procedure, sample can be heated, cools off or vibrates.

In the gene magnification of PCR-based method is handled, repeat heating and cooling.Because elastic membrane 110a is thin, and directly carries out heating and cooling to sample by the elastic membrane 110a that adheres to, so repercussion is far faster than traditional indirect and cooling method.

In this manner, be to form iff the elastomer that is target chamber top, and be stained with outer anchor clamps 200a on the film that then heating and cooling or vibration can be applied on the sample by 1mm or less than the film of 1mm.Because heating and cooling only act directly on the sample, almost do not have transmission, influence other parts hardly, therefore can realize high-speed response.And vibration only acts directly on the sample, does not almost have transmission, influences other parts hardly.

Notice that the present invention is not limited to the foregoing description.For example, as shown in figure 49, the internal pressure of chamber A can be produced by press down (or intervention) of outer anchor clamps.In this case, inlet fluid passage 115j that forms with equidirectional in the A of chamber and outlet fluid passage 115k are flattened by roller 130 (as plug valve) simultaneously, and chamber A is sealed, then outer anchor clamps 200a is pressed onto on the elastic membrane, thus the internal pressure of rising chamber A.

Shown in Figure 50 (a), outside anchor clamps 200a contact area around can form groove 110b in the elastic part so that reduce heat or the vibration that is delivered on the other parts.Perhaps, shown in Figure 50 (b), can in groove, imbed by heat-barrier material or filling member 110c that the material that shakes is extremely made.

Perhaps, shown in Figure 51, elastic membrane can be formed by hyaline membrane.If the use hyaline membrane can utilize reading device 400 by the fluorescence in window (elastic membrane 110a) the observation DNA crossover process of hyaline membrane.If sample is heated, can inject laser by window, do not use outer anchor clamps.

It is wrinkling or do not contain bubble to remove non-elastomeric film 110a, and the internal pressure of chamber almost is an atmospheric pressure.

For capture dna, silica beads or materials similar can be used for magnetic bead.In this case, can use less than the filter of pearl and catch pearl itself.

Embodiment is opposite therewith for vertical relation between box and the outer anchor clamps.In other words, the top and bottom of box can be put upside down, and makes outer anchor clamps press to elastic membrane 110a from below.

Elastomer is exerted pressure, be not limited to utilize roller shown in above-mentioned embodiment the pressurization of the gamut of box.External force can apply from the outside of container, partly close fluid passage, chamber or partly close the two simultaneously, thereby fluid passage or indoor flowing material can move or get clogged.

The pump or the valve that play this effect are not to be limited to external force, can also use at the outer pump of box outside or the internal valve of being made by marmem or similar material.

Since the box of said structure be sealing with disposable, so they virus or dangerous drug are security structures relatively.In addition, from actual angle, these boxes are very useful, because the predetermined rules that they can make chemical reaction or similar procedure can realize simply, and do not have difference between the operator.

Claims (5)

1. cartridge for chemical reaction drive unit, wherein said cartridge for chemical reaction is the cartridge for chemical reaction that is used to carry out chemical reaction of samples, comprise: by rigid matrix and elastomer, the perhaps container that forms by rigid matrix and plastic body, wherein form two or more chambers, these chambers are communicated with, perhaps be arranged to and be communicated with by the fluid passage, when the external force from described external container acts on described elastomer or the described plastic body, make described fluid passage, described chamber or the two are partly closed, thereby the flowing material in described fluid passage or the described chamber can be moved or get clogged;

It is characterized in that the fluid passage of described cartridge for chemical reaction, chamber or this two come partly closedly by mechanical device, be used to suck sample or be used for moving or blocking described fluid passage or indoor flowing material.

2. cartridge for chemical reaction drive unit as claimed in claim 1 is characterized in that, uses one or more cylindrical rolls, ball, barrel-shaped pressing means, circular arc pressing means or tabular increased pressure board, and described mechanical device is to described elastomer or the pressurization of described plastic body.

3. cartridge for chemical reaction drive unit as claimed in claim 1 is characterized in that, utilizes at least one pair of actuator of operating on one or more dimensions, drives a rigid body by described mechanical device, to described elastomer or the pressurization of described plastic body.

4. as claim 2 or 3 described cartridge for chemical reaction drive units, it is characterized in that described elastomer is a viscoelastic body.

5. cartridge for chemical reaction drive unit as claimed in claim 1, it is characterized in that, pressing mechanism, as described in being embedded in as actuator, rigid body, PZT or marmem in the container, be used to provide described mechanical device, and use is united in described pressing mechanism and external drive, is used for partly closing fluid or chamber.

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