Summary of the invention
It is a kind of be used to utilizing the bar magnet method to extract the work system of the self-reacting device of biologically active substance that the utility model provides, and the self-reacting device that adopts the extraction biologically active substance of described work system, work system of the present utility model can be applicable to multiple fields such as clinical disease diagnosis, transfusion safety, medical jurisprudence evaluation, environmental microorganism detection, food safety detection, molecular biology research, be used for extracting and purifying biological active substance, for example cell, albumen and nucleic acid.The design of work system of the present utility model and instrument makes the automatization of nucleic acid extraction instrument further improve, and can be suitable for various type culture plates simultaneously, and the needs that can be used for indivedual or big flux nucleic acid extraction simultaneously.
The instrument that be used for to extract biologically active substance generally includes the worktable that holds sample and reagent for placement, and needle and needle travel mechanism by moving up and down of needle travel mechanism, make needle to move up and down, and vertically inserts and breaks away from sleeve pipe; Sleeve pipe and sleeve pipe travel mechanism by moving up and down of sleeve pipe travel mechanism, make sleeve pipe to move up and down, and vertically insert and break away from the container that is arranged on worktable.Use described instrument to extract biologically active substance, when for example extracting nucleic acid, can add biological sample and/or reagent at the container (for example centrifuge tube, deep-well plates etc.) that is placed on the worktable, then by sleeve pipe moving up and down or vibrate in container, can to the reagent in the container and sample stir and mixing, so that sample and reagent fully react.Can make sleeve pipe produce magnetic field outward thus by sleeve pipe and needle are inserted container simultaneously in addition, thereby realize that sleeve pipe is to the absorption of the biological sample of the magnetic bead in the solution in the container or band magnetic bead.When needle left sleeve pipe, the sleeve pipe foreign field disappeared, thereby the biological sample of realizing magnetic bead or band magnetic bead breaks away from sleeve pipe, namely discharges the biological sample of magnetic bead or band magnetic bead.Thus can be mobile in different vessels by sleeve pipe and needle, reach the purpose of the biological sample that shifts magnetic bead or band magnetic bead.
The utility model provides a kind of work system for the biologically active substance extraction apparatus, it has the loading panel, have at least one group of sample preparation district on the described loading panel, every group of described sample preparation district has two heating work district and middle non-heating work districts, described two heating work districts that are fixed on the described loading panel.Two heating work districts that are fixed on the described loading panel can be set in parallel in the two ends in described sample preparation district.
Aspect one of the present utility model, heating work district described in the described work system is heating tank, every group of sample preparation district has two heating tanks that are fixed on the loading panel, is respectively heating tank 1, heating tank 2 65 and the middle non-heating work district of this two heating tanks.Heating tank 1, heating tank 2 65 can be set in parallel in the two ends in sample preparation district.Described non-heating work district can have or the container that holds sample or reagent is set.Aspect one of them, the described container that holds sample or reagent is 24 holes or standard deep plates such as 96 hole PCR microwell plates or deep-well plates of the present utility model, non-standard orifice plate, and centrifuge tube or centrifuge tube connection pipe maybe can be placed the plate of described centrifuge tube or centrifuge tube connection pipe.
Aspect one of the present utility model, heating work district described in the above-mentioned work system is heating tank removably, and it has the rectangular parallelepiped cell body, which is provided be used to a plurality of slotted eyes of laying sample hose.Aspect one of them, the cell body of described heating tank bottom has the heating tank projection of the present utility model, can with the loading panel on groove fit.Aspect one of them, the cell body temperature range of above-mentioned heating tank is about 100-200 ℃, is preferably about 120-180 ℃ of the present utility model.
Aspect one of the present utility model, has heat insulation between heating work district and the non-heating work district in the above-mentioned work system.
Aspect one of the present utility model, heating work district described in the above-mentioned work system separates effectively with non-heating work district, effectively separate and refer to, the zone that heating work district and non-heating work district hold pending sample or reagent on workplatform at a distance of certain distance, so that the heat that the heating work district produces can not produce effective influence to the sample of handling in non-heating zone.
Effectively separate referring to, the zone that heating work district and non-heating work district hold pending sample or reagent on workplatform at a distance of certain distance, so that the heat that the heating work district produces can be to the sample generation effective influence of handling in non-heating zone.Of the present utility model aspect one of them, the setting in heating work district (for example heating tank) can so that two heating work districts with near the non-heating work of being placed on of its district or the hole that is used for holding sample or reagent that has, non-heating work district (for example be arranged on the hole of the most close heating zone of 24 holes of non-heating zone or 96 hole PCR microwell plates or deep-well plates, or be arranged in the centrifuge tube of non-heating zone or the centrifuge tube connection pipe hole etc. of the most close heating zone) distance B greater than about 5mm, be preferably greater than about 10mm, most preferably greater than about 15mm.For example D is about 5-60mm, preferably about 10-40mm, most preferably from about 15-35mm.Wherein, term " for the hole that holds sample or reagent " refers to hold be used to the container that holds sample or reagent the hole of sample or reagent, and it can be the form of shrinkage pool, well or groove." effective influence " generally refers to the sample that handles non-heating zone because the heat that the heating work district produces causes influencing the volume change that temperature rises and/or sample evaporation causes of reaction etc.
Aspect one of the present utility model, two be arranged in parallel and are fixed on distance B 1 between the heating zone (for example heating tank) on the loading panel greater than 90mm, are preferably greater than 105mm, most preferably greater than 120mm.For example D1 is about 90-160mm, preferably about 105-150mm, most preferably from about 120-140mm.Preferably, described heating zone is heating tank, and the width between centers D2 of two heating tanks is preferably greater than about 115mm greater than about 110mm, most preferably greater than about 120mm.For example D2 is about 110-200mm, preferably about 115-180mm, most preferably from about 120-160mm.
Aspect one of the present utility model, not contact of that heating zone (for example heating tank) and non-heating zone have or the container that is used for holding sample or reagent that is arranged on non-heating zone (for example be arranged on 24 holes or 96 hole PCR microwell plate or the deep-well plates of non-heating zone, or be arranged on the centrifuge tube of non-heating zone or centrifuge tube connection pipe etc.).Preferably, heating zone (for example heating tank) is greater than about 3mm with the container distance B 3 for holding sample or reagent that is placed on non-heating zone, is preferably greater than about 10mm, most preferably greater than about 15mm.For example D3 is about 3-60mm, preferably about 10-40mm, most preferably from about 15-35mm.Aspect one of them, between heating zone and non-heating zone, also has heat insulation of the present utility model.
Aspect one of the present utility model, having two in the above-mentioned work system in described sample preparation district 66 be arranged in parallel and is fixed on heating tank on the loading panel, be respectively heating tank 1, heating tank 2 65, and one 24 or 96 hole PCR microwell plate or deep-well plates of horizontal positioned between described two heating tanks, or a plate of placing centrifuge tube or centrifuge tube connection, the long limit of wherein said PCR microwell plate or deep-well plates or plate is parallel with heating tank.Described can be to be placed between two parties between described two heating tanks.Described 24 or 96 hole PCR microwell plates or deep-well plates can be on-gauge plates, for example meet 96 hole on-gauge plates of the parameter of ANSISBS1-42004 standard.24 orifice plates are 4 * 6 types, namely have 6 holes of the 4 every rows of row.24 orifice plate apertures can be about 18mm, and plate is rectangle, and the length of its housing is about 127.76mm ± 0.25mm, and wide is about 85.48mm ± 0.25mm.96 orifice plates are 8 * 12 types, namely have 12 holes of the 8 every rows of row.96 orifice plate apertures can be about 9mm, and plate is rectangle, and the length of its housing is about 127.76mm ± 0.25mm, and wide is about 85.48mm ± 0.25mm.Aspect one of the present utility model, in the above-mentioned work system two heating tanks with near its 24 holes or 96 hole PCR microwell plates or deep-well plates in the distance B in the hole of close heating tank greater than 5mm, be preferably greater than 10mm, most preferably greater than 15mm, for example D is about 5-60mm, preferred about 10-40mm, most preferably from about 15-35mm.Aspect one of the present utility model, the frame of wherein said PCR microwell plate or deep-well plates or plate and its distance B 3 at a distance of nearer heating tank are greater than about 3mm, are preferably greater than about 10mm, most preferably greater than about 15mm.For example D3 is about 3-60mm, preferably about 10-40mm, most preferably from about 15-35mm.
Aspect one of the present utility model, be horizontally disposed with one 24 or 96 hole PCR microwell plate or deep-well plates between two heating tanks described in the above-mentioned work system, the long limit of wherein said PCR microwell plate or deep-well plates or plate is parallel with heating tank.
Aspect one of the present utility model, have two heating tanks that are fixed on the loading panel described in the above-mentioned work system in the sample preparation district 66, be respectively heating tank 1, heating tank 2 65, each heating tank has 1-5 slotted eye.Horizontal parallel arranges one to five tetrad pipe or centrifuge tube tetrad pipe between described two heating tanks.4 centrifuge tubes are arranged on the described tetrad pipe.Choose wantonly, between the slotted eye of heating tank one and corresponding tetrad pipe, a centrifuge tube can be set also.
The bar magnet method is extracted biologically active substance, and the method for for example extracting nucleic acid generally includes following steps: a) by sample is contacted with lysate (lysis buffer) and/or Proteinase K, at about 50-60 ℃ of following incubation, cracking biological sample; B) add magnetic bead, before use abundant mixing magnetic bead; C) add in conjunction with liquid (binding buffer), leave standstill; D) use washings I(wash buffer I respectively), cleaning solution II (wash buffer II) and cleaning solution II I(wash buffer III) washing three times; E) with elutriant (elution buffer) wash-out nucleic acid.
When being used for some biomaterial (for example virus) extraction nucleic acid, can join in the lysate in step a) in conjunction with liquid, namely step c) can merge to step a).When being used for some biomaterial (for example virus) extraction nucleic acid, at step b) and d) between have step into nucleic acid settling agent (Acryl Carrier).
Reagent wherein, as lysate (lysis buffer), in conjunction with liquid (binding buffer), washings I-III(wash buffer) and elutriant (elution buffer) can place in advance/seal up for safekeeping in container, also can extract preceding adding.Magnetic bead usually needs carry out the container that holds magnetic bead before use centrifugal, so that the abundant mixing of magnetic bead or concentrate on this container bottom.
Using instrument of the present utility model to extract biologically active substance, when for example extracting nucleic acid, can add biological sample and/or reagent at the container (for example centrifuge tube, deep-well plates etc.) that is placed on the worktable, then by sleeve pipe moving up and down or vibrate in container, can to the reagent in the container and sample stir and mixing, so that sample and reagent fully react.Can make sleeve pipe produce magnetic field outward thus by sleeve pipe and needle are inserted container simultaneously in addition, thereby realize that sleeve pipe is to the absorption of the biological sample of the magnetic bead in the solution in the container or band magnetic bead.When needle left sleeve pipe, the sleeve pipe foreign field disappeared, thereby the biological sample of realizing magnetic bead or band magnetic bead breaks away from sleeve pipe, namely discharges the biological sample of magnetic bead or band magnetic bead.Thus can be mobile in different vessels by sleeve pipe and needle, reach the purpose of the biological sample that shifts magnetic bead or band magnetic bead.
Using instrument of the present utility model to extract biologically active substance, for example extract in the method for nucleic acid, generally include following steps: a) by sample is added the container a that holds lysate (lysis buffer), at about 50-60 ℃ of following incubation; B) by needle and sleeve pipe with magnetic bead from the container b that holds magnetic bead with magnetic bead absorption with transfer to said vesse a, optional, using the centrifugal container that holds magnetic bead; C) optional, by needle and sleeve pipe with the magnetic bead among the container a or in conjunction with the sample absorption of magnetic bead with transfer to the container c that holds in conjunction with liquid (binding buffer); D) adsorb successively and transfer to and hold washings I(wash bufferI with above-mentioned magnetic bead or in conjunction with the sample of magnetic bead), cleaning solution II (wash buffer II) and cleaning solution II I(wash buffer III) container d1, container d2 and container d3; E) will be through the magnetic bead in the step d) or in conjunction with the absorption of the sample of magnetic bead with transfer to the container e that holds elutriant (elution buffer), about 50-60 ℃ of following incubation.When being used for some biomaterial (for example virus) extraction nucleic acid, can join in the lysate in step a) in conjunction with liquid, namely step c) can merge to step a).Be used for some biomaterial (for example virus) when extracting nucleic acid, step b) and d) between have magnetic bead or adsorb and transfer to the step of the container that holds nucleic acid settling agent (Acryl Carrier) in conjunction with the sample of magnetic bead.
Aspect one of the present utility model, in the above-mentioned work system, can in heating tank one, be provided for holding the container (for example lysate centrifuge tube) of lysate.In addition, can be provided for receiving the container (for example elutriant centrifuge tube) of elutriant at heating tank two.In addition, can be in described 24 or 96 hole PCR microwell plate or the deep-well plates in non-heating work district, or place in the plate of centrifuge tube or centrifuge tube connection and can set gradually the hole that holds washings I, cleaning solution II and cleaning solution II I.Choose wantonly, can also be in described 24 or 96 hole PCR microwell plate or deep-well plates, or place to arrange in the plate of centrifuge tube or centrifuge tube connection and hold magnetic bead or in conjunction with the hole of liquid or nucleic acid settling agent.
Aspect one of the present utility model, above-mentioned work system has driving mechanisms control, can move in the horizontal direction.Of the present utility model aspect one of them, wherein said drive mechanism system comprises the support of table, is used for supporting the loading panel, and support is connected with shifting axle, can move horizontally along shifting axle at worktable driven by motor lower bracket, thereby make the position that the loading panel can move to be needed.
Aspect one of the present utility model, above-mentioned work system also has:
Shell,
Base plate,
Needle and needle travel mechanism by moving up and down of needle travel mechanism, make needle to move up and down, vertically insert and break away from sleeve pipe,
Sleeve pipe and sleeve pipe travel mechanism by moving up and down of sleeve pipe travel mechanism, make sleeve pipe to move up and down, and vertically insert and break away from the container that is arranged in the sample preparation district.
Aspect one of the present utility model, above-mentioned work system comprises that also air-flow produces system, described system is used for producing local air flow at the upper area of the opening that is placed on the container that holds sample or reagent in the described sample preparation district, described system comprises air flow source and gas channel, wherein air flow source can produce air-flow, the upper area of the opening of the bootable described flow level of gas channel by described container, the aerosol that makes sample in sleeve pipe and the container or reagent contacts generation moves horizontally after vessel port release.The speed of described local air flow can be about 0.3-0.8 meter per second, preferably about 0.5-0.7 meter per second, most preferably from about 0.45-0.5 meter per second.
Of the present utility model aspect one of them, the perforate of horizontal symmetrical is set in two opposing sideplates of described work system shell, form the gas channel that described air-flow produces system, the position that perforate wherein is set makes the upper area of the opening that the air-flow by the horizontal flow of these two perforates can be by being placed on the container in the sample preparation district.Aspect one of them, wherein the described loading panel upper surface of the distance from bottom of perforate is high about 0-50mm, preferably 3-15mm, most preferably from about 5-10mm of the present utility model.
Aspect one of them, perforate can be pore district, for example rectangle pore district of the present utility model.The length in rectangle pore district (being the horizontal length in pore district) adapts with the container that is placed in the sample preparation district.In wherein a kind of embodiment of the present utility model, it is identical or close with the length of supported arm that the length in rectangle pore district is set to.In wherein a kind of embodiment of the present utility model, the length in rectangle pore district be set to be placed on the loading panel on 24 orifice plates or the long limit of 96 orifice plates (the 96 hole on-gauge plates that for example meet the parameter of ANSISBS12004 and ANSISBS22004 standard) equates or greater than described long limit., preferred, the length in described rectangle pore district for example for about 127-140mm, is preferably about 128-135mm greater than about 127.76mm.The width in rectangle pore district (being the vertical length in described pore district) is set to take into account the height that is placed on the container in the sample preparation district of various height.In wherein a kind of embodiment of the present utility model, the width in rectangle pore district is set to about 30-80mm, is preferably about 40-70mm, most preferably is about 50-65mm.
The height of the distance from bottom loading panel upper surface in rectangle pore district is identical with the top of container on being placed on the sample preparation district or a little less than described top.For example, the bottom of aperture area is set than the about 0-15mm of loading surface plate hight, preferred 3-10mm, most preferably 5-10mm.
In other embodiment of the present utility model, can be by the height that perforate is adjusted in perforate moving up and down be set at side plate, make the air-flow of the horizontal flow by these two perforates can upwards be placed on the upper area of the opening of the container in the sample preparation district by opening.
In other embodiment of the present utility model, can be by Work platform system moving up and down be set, make the loading panel can adjust height, make that the upper area of the opening be placed on the container in the sample preparation district is same or similar with the level attitude by two perforates.
In another kind of embodiment of the present utility model, wherein gas channel also comprises and being arranged on outside the tool housing, and with the conduit that described perforate is connected, an end of described conduit is connected with perforate, and the other end is connected with specified location.In another kind of embodiment of the present utility model, at the arranged outside conduit of tool housing side plate perforate.The outer fringe seal of the perforate on one end of described conduit and the outer panel is connected, and the other end is connected with specified location.In a kind of embodiment of the present utility model, an end that connects the conduit of the perforate of giving vent to anger is connected with described perforate, the other end opening is arranged on the designated area, for example with interatrial septum, instrument place from the room, can only enter the designated area along conduit from the instrument internal effluent air, guarantee thus in the instrument biological substance for example nucleic acid can not pollute room, instrument place.In a kind of embodiment of the present utility model, one end of the conduit of the perforate of connection air inlet is connected with described perforate, the other end opening in interatrial septum, instrument place from the room or the zone of pollution-free gas is provided, thus, the gas that guarantees to enter instrument internal or room, instrument place thus is not subjected to the pollution of other biological substance.
Aspect one of the present utility model, the air flow source that wherein said air-flow produces system is fan.
Aspect one of the present utility model, wherein said fan is arranged in the perforate of side wall of outer shell, is configured to produce the air-flow of horizontal flow.Of the present utility model aspect one of them, in two perforates of side wall of outer shell fan is set all, one of them fan is supply fan, and the air-flow of generation is for entering instrument internal from the instrument outside, another is extraction fan, and the air-flow of generation is for to enter the instrument outside from instrument internal.In another embodiment of the present utility model, can have only supply fan or extraction fan.
In another embodiment of the present utility model, the air flow source that described air-flow produces system also can be for draught head produces system, for example the mechanism of the generation negative pressure of setting the perforate of giving vent to anger outside.
Aspect one of the present utility model, at the arranged outside filter screen grid of supply fan.Aspect one of the present utility model, at the arranged outside filter screen grid of supply fan.Aspect one of them, the size of mesh of described filter screen grid is generally more than or equal to about 0.045mm of the present utility model.Aspect one of them, the filter screen order number of described filter screen grid is for being less than or equal to 325 orders of the present utility model.
In one aspect, of the present utility model for the instrument that extracts biologically active substance, the speed of the local air flow that the upper area of the opening of the container of described air-flow generation system in the sample preparation district produces is about 0.3-0.8 meter per second, preferred about 0.5-0.7 meter per second, most preferably from about 0.45-0.5 meter per second.
In one aspect, in the work system of the present utility model, described air-flow produces the aerosol that has biological sample that local air flow that the upper area of the opening of the container of system in the sample preparation district produces can prevent that sleeve pipe from contact generation with liquid in the container and floats to and cause pollution in other container.
Aspect one of the present utility model, air-flow described in the above-mentioned work system of the present utility model produces system and also has Controlling System, the generation that is used for the described local air flow of control whether with the speed of the air-flow that produces.Preferably, when described Controlling System can and be left the container that is placed in the sample preparation district in sleeve pipe and/or needle rising, make local air flow generation system stop to produce the air-flow of horizontal flow.
Aspect one of them, needle described in the described work system is permanent magnet material of the present utility model.
Aspect one of them, sleeve pipe described in the described work system is nonmagnetic substance of the present utility model.
Aspect one of them, wherein said biologically active substance is cell, protein or nucleic acid of the present utility model.
Of the present utility model aspect one of them, described work system is used for extracting and the instrument of purification of nucleic acid.
Aspect one of the present utility model, the method of using above-mentioned work system for the biologically active substance extraction apparatus to extract with the purifying biological active substance may further comprise the steps: described work system or described instrument are provided, the container that is used for holding sample or reagent is placed in sample preparation district at work system loading panel, in described container, hold sample or reagent, thereby the sleeve pipe by the biologically active substance extraction apparatus and/or needle insert and break away from that the container that is placed in the sample preparation district realizes shifting magnetic bead or in conjunction with the biological substance of magnetic bead.Choose wantonly, thereby wherein also comprise the container internal vibration on being placed on the sample preparation district of sleeve pipe and/or needle to the reagent in the container and/or sample stirs and mixing, so that the step that sample and reagent fully react.Can comprise also in the using method of the present utility model by local air flow producing the step that system upwards is placed on the opening of the container in the sample preparation district at opening upper area produces the local air flow of horizontal flow that the aerosol that makes sample in sleeve pipe and the container or reagent contacts generation moves horizontally after vessel port release.Of the present utility model aspect one of them, when sleeve pipe and/or needle raise and leave the container that is placed in the sample preparation district, above-mentioned local air flow generation system stopped to produce the air-flow of horizontal flow.
Embodiment
In order to understand better and to explain the utility model, below with reference to accompanying drawings the utility model is described in further detail.
Fig. 1 and Fig. 2 are the internal structure stereographic maps that adopts the instrument that is used for the extraction biologically active substance of work system of the present utility model.
Described preferred embodiment instrument of the present utility model can be used for extracting and purification of nucleic acid.This instrument has base plate 1, needle 7 and needle travel mechanism 48, sleeve pipe 4 and sleeve pipe travel mechanism 16 are for the support 13 that supports described needle travel mechanism and sleeve pipe travel mechanism, and for generation of vibration, make sleeve pipe travel mechanism carry out the vibrating mechanism 19 of up-down vibration.
Sleeve pipe is the pipe with closed bottom and hollow tube chamber.Sleeve pipe can have for example elongated cylinder form.The material of sleeve pipe is normally nonmagnetic.The selection of its material and thickness and be designed to not weakened field or only influence magnetic field a little, but need guarantee when needle inserts, can attract in the outer generation of sleeve pipe the magnetic field of the biological sample of magnetic bead or band magnetic bead.
Needle can vertically insert and break away from sleeve pipe.The bottom of needle (namely inserting an end of sleeve pipe) has magnetic.When needle inserts and contact or during near sleeve bottom, can produce magnetic field outside sleeve pipe, thereby realize that sleeve pipe is to the magnetic bead in the outer solution of sleeve pipe or absorption and the disengaging of being with the biological sample of magnetic bead.In the present embodiment, the bottom of needle has permanent magnet, has magnetic thus.In other embodiment of the present utility model, needle can produce magnetic (electromagnet) by electromagnetic action.
Described have the work system 15 that can move horizontally for the instrument that extracts biologically active substance.In other embodiment of the present utility model, work system can be fixed, and for example is fixed on the instrument base, and can realize needle and sleeve pipe moving relative to worktable this moment by moving horizontally of needle and cannula system.
Fig. 3 is the stereographic map of the instrument that is used for the extraction biologically active substance of above-mentioned employing the utility model work system, has wherein shown the instrument that comprises the mechanism on its shell and the shell.
The shell that illustrates instrument of the present utility model has top board 71, side plate 73, backboard 72 and panel 75.Shell is generally metallic substance, and for example stainless steel or aluminium alloy are made.Have sample introduction window 76 on the panel in the right on of instrument of the present utility model, be used for putting into and taking out sample.The sample introduction window has the hatch door made from transparent material (not illustrating at accompanying drawing).Hatch door can make progress easily left or right open and close.Shell can have viewing window, the situation that supplies operator's observation experiment to carry out.In diagram preferred embodiment of the present utility model, sample introduction window and viewing window are same parts.
The shell that illustrates instrument of the present utility model has user interface, the display screen 74 that for example is connected with control device.
Shell also can have the external apparatus interface that is connected with peripheral equipment in addition, various manipulation of switches, button or button etc.
Fig. 4 is the front view of the instrument that is used for the extraction biologically active substance of above-mentioned employing the utility model work system.Work system 15 has loading panel 67.The movement of the worktable that can move horizontally can be moved in the horizontal direction by movable workbench driving mechanism 60 controls that are arranged at loading panel below.Thereby make the container in sample preparation district can move to the below of sleeve pipe, sleeve pipe can vertically insert and break away from the container in the sample preparation district, centrifuge tube for example, PCR plate and deep-well plates etc.Described drive mechanism system comprises the support of table 61, props up to be set up in loading surface plate below, is used for supporting the loading panel.Shifting axle 62 passes support 61, driving lower bracket at movable workbench mechanism motor 63 can move horizontally along shifting axle, thereby make the position that the loading panel can move to be needed, namely make the pipe or the hole that are placed on the container on the loading panel move to the sleeve pipe below according to time variable control.
Fig. 5 is the cross sectional plan view that the bar magnet method is extracted the instrument of biologically active substance that is used for of above-mentioned employing the utility model work system.Fig. 6 a-6c is the vertical view according to the worktable of the utility model preferred embodiment, wherein is provided with the container that holds sample or reagent at the loading panel.
As shown in the figure, work system 15 has loading panel 67, has two sample preparation districts 66 on it.Each sample preparation district 66 has two heating tanks that are fixed on the loading panel 67 at its two ends, left and right sides: heating tank 1, heating tank 2 65.The sample preparation district is used for being provided for holding the container of sample or reagent, as Eppendorf tube, centrifuge tube, PCR microwell plate, deep-well plates, micro-porous filtration plate, pipe support etc., described container can be standard container, the experimental ware of ANSI/SBS standard for example also can non-standard container.
The PCR microwell plate is a kind of culture plate that is applicable to paramagnetic particle method.The length of the housing of the plate of common PCR microwell plate is about 127.76mm ± 0.25mm, and wide is about 85.48mm ± 0.25mm.The height of the plate of common PCR microwell plate is about 14.35mm ± 0.76mm.For example, the 96 hole Standard PC R microwell plates that have the parameter that meets ANSI SBS1-42004 standard.
Deep-well plates is the another kind of culture plate that is applicable to paramagnetic particle method, has the hole darker than PCR microwell plate.The length of the housing of the plate of common deep-well plates is about 127.76mm ± 0.25mm, and wide is about 85.48mm ± 0.25mm.For example, the 96 hole standard deep culture plates that have the parameter that meets ANSI SBS1-42004 standard.The height of the plate of common deep-well plates is about 30-50mm, for example about 32mm and 43mm.
In illustrated preferred embodiment instrument of the present utility model, worktable has two groups of sample preparation districts 66, corresponding two groups of needles and sleeve pipe.Each sample preparation district 66 of work system of the present utility model has two heating work districts 2 that are fixed on the loading panel 67 at its two ends, left and right sides, and the non-heating work district 3 in the middle of these two heating work districts.Aspect one of the present utility model, the heating work district is heating tank.In illustrated preferred embodiment instrument of the present utility model, every group of sample preparation district 66 comprises the non-heating work district 3 in the middle of heating tank 1, heating tank 2 65 and this two heating tanks that are fixed on the loading panel respectively.
In a kind of embodiment of the present utility model, non-heating work district 3 comprises the loading panel that is arranged in two heating tanks, be used for placing the container that holds sample or reagent, standard deep plate such as 24 holes or 96 hole PCR microwell plates or deep-well plates for example, also can place non-standard orifice plate, or single, a plurality of or single centrifuge tube or centrifuge tube connection pipe, and the plate etc. that can place described centrifuge tube or centrifuge tube connection pipe.Non-heating work district 3 can have for the fixing described locating device that holds the container of sample or reagent.In one embodiment, can fixed block 82 be set in the front and back side in non-heating work district, be suitable for limiting described container moving forward and backward on carrier table of holding sample or reagent.Before and after fixed block distance and the described container that holds sample or reagent for example deep-well plates and length width identical.Can have spring on the fixed block inboard.In another embodiment, the front and back side in non-heating work district arranges elastic clip, utilizes elastic deformation to compress culture plate at fore-and-aft direction, limits its moving forward and backward on carrier table.
In a kind of embodiment of the present utility model, non-heating work district 3 has the container that holds sample or reagent for placement, standard deep plate such as 24 holes or 96 hole PCR microwell plates or deep-well plates for example, or sketch plate, or single, a plurality of or single centrifuge tube or centrifuge tube connection pipe, and the plate that can place described single, a plurality of or single centrifuge tube or centrifuge tube connection pipe.
In other embodiment of the present utility model, non-heating work district also can have perforation or groove, perforation or quantity, position and the size of groove can be suitable for quantity, position and the size in the hole of the described container that holds sample or reagent, make described container can insert described perforation or groove, reach the effect of fixing described container.
Each sample preparation district 66 of work system of the present utility model is provided with two heating work districts 2 that are fixed on the loading panel at its two ends.The heating work district can be provided for holding the container of sample or reagent, as Eppendorf tube, centrifuge tube.The heating work district can heat described container.In illustrated work system of the present utility model, the heating work district is heating tank removably, is respectively heating tank 1 and heating tank 2 65.Heating tank can adopt the material preparation of heat conduction, for example metal such as stainless steel, aluminium.Heating tank has the rectangular parallelepiped cell body, is provided be used to a plurality of slotted eyes of laying sample hose in mode placed in the middle on it.It is corresponding that being used for of the degree of depth of slotted eye and aperture and the slotted eye that is suitable for being placed on heating tank held height and the aperture of container of sample or reagent.The slotted eye of heating tank be used for hold height and the aperture of container of sample or reagent can be corresponding with the container of placing in non-heating work district.Aspect one of the present utility model, the aperture of container that is placed on the slotted eye of heating tank has the aperture identical with the pipe of the container of placing in non-heating work district or hole.Aspect one of the present utility model, heating tank and be placed on heating tank slotted eye container be arranged so that described container insert slotted eye after its mouth of pipe same or similar with the height of the container of placing in non-heating work district apart from the height of loading panel upper surface, namely make the upper surface basic horizontal of mouth of pipe height and the container of non-heating work district placement of container of the slotted eye that is placed on heating tank.
Heating tank is removably, can change the heating tank with different quantities slotted eye and different apertures according to different processing objects.For example, corresponding 24 holes and 96 hole PCR microwell plates or deep-well plates can adopt the heating tank with 6 or 12 slotted eyes.Heating tank can be by for example being located at cell body bottom the heating tank projection and the groove fit on the loading panel.The length of the groove on the loading panel, width and the degree of depth can be fixed, can be fixed at length, width and the height of the projection of cell body bottom thus, and just change length and the width of cell body, what just can obtain to can be used for same loading panel a series ofly has the slotted eye of different radii or quantity and is suitable for the heating tank of different application objects.
Arranging of heating tank can exceed the loading panel surface, and for example the heating tank cell body is positioned at the loading panel surface, and heating tank projection projection embeds the loading panel.Heating tank also can all embed the loading panel, and for example the heating tank upper surface is parallel with the loading panel surface.
The cell body of heating tank can heat by various modes commonly used.For example, the metal heating tube that passes whole cell body along the cell body length direction can be set in lower part of cell body, make heating tube produce heat by the electric heating effect, thereby whole cell body temperature is risen, so that the sample hose that is placed in the cell body is heated.In addition, for example can be by semiconductor temperature-control (or being called electronic temperature control) mode.The work running of semiconductor temperature-control is with the galvanic current heating, decides at same cooling piece by the polarity that changes galvanic current and realizes heating.The temperature of cell body can be up to about 200 ℃, and common temperature range is about 100-200 ℃, are preferably about 120-180 ℃.
Of the present utility model aspect one of them, around heating tank, heat insulation can be set, one side can prevent operator's Contact Heating groove and come to harm, can prevent that on the other hand heat is transmitted to non-heating work district, influence the temperature condition of the reaction in the container in non-heating work district, and prevent from causing being placed on solution evaporation in the container in non-heating work district, also influence the reaction conditions in the container.The solar heat protection piece can for example rubber or plastics be made by athermanous material.
Aspect one of the present utility model, the heat insulation of heating tank can be used for limiting the position of the container that holds sample or reagent that is placed on non-heating work district 3.For example, heat insulation is the rectangular parallelepiped of hollow, and heating tank can embed the hollow space of heat insulation.The thickness of the frame of heat insulation can be arranged so that between the heat insulation of two heating tanks distance with to the container that is placed on non-heating work district (standard deep plate or sketch plate such as 24 holes or 96 hole PCR microwell plates or deep-well plates for example, or place the plate etc. of centrifuge tube or centrifuge tube connection pipe) width identical, limit the move left and right of described container thus.
One of them advantage of the present utility model is, the sample of handling in heating work district and non-heating work district that is arranged so that in two heating work districts at non-heating work district and its two ends separates effectively.Effectively separate referring to, the zone that heating work district and non-heating work district hold pending sample or reagent on workplatform at a distance of certain distance, so that the heat that the heating work district produces can be to the sample generation effective influence of handling in non-heating zone.Of the present utility model aspect one of them, the setting in heating work district (for example heating tank) can so that two heating work districts with near the non-heating work of being placed on of its district or the hole that is used for holding sample or reagent that has, non-heating work district (for example be arranged on the hole of the most close heating zone of 24 holes of non-heating zone or 96 hole PCR microwell plates or deep-well plates, or be arranged in the centrifuge tube of non-heating zone or the centrifuge tube connection pipe hole etc. of the most close heating zone) distance B greater than about 5mm, be preferably greater than about 10mm, most preferably greater than about 15mm.For example D is about 5-60mm, preferably about 10-40mm, most preferably from about 15-35mm.Wherein, term " for the hole that holds sample or reagent " refers to hold be used to the container that holds sample or reagent the hole of sample or reagent, and it can be the form of shrinkage pool, well or groove." effective influence " generally refers to the sample that handles non-heating zone because the heat that the heating work district produces causes influencing the volume change that temperature rises and/or sample evaporation causes of reaction etc.In the prior art, adjacent two of same culture plate (or two rows) sample wells are heated respectively and heat treated not, can cause the rising of temperature in the sample well that does not need to heat like this, thereby cause the extraction effect of biological sample to become bad.
Aspect one of the present utility model, the distance B 1 between two heating zone (for example heating tank) is preferably greater than 105mm, most preferably greater than 120mm greater than 90mm.For example D1 is about 90-160mm, preferably about 105-150mm, most preferably from about 120-140mm.Preferably, described heating zone is heating tank, and the width between centers D2 of two heating tanks is preferably greater than about 115mm greater than about 110mm, most preferably greater than about 120mm.For example D2 is about 110-200mm, preferably about 115-180mm, most preferably from about 120-160mm.
Aspect one of the present utility model, not contact of that heating zone (for example heating tank) and non-heating zone have or the container that is used for holding sample or reagent that is arranged on non-heating zone (for example be arranged on 24 holes or 96 hole PCR microwell plate or the deep-well plates of non-heating zone, or be arranged on the centrifuge tube of non-heating zone or centrifuge tube connection pipe etc.).Preferably, heating zone (for example heating tank) is greater than about 3mm with the container distance B 3 for holding sample or reagent that is placed on non-heating zone, is preferably greater than about 10mm, most preferably greater than about 15mm.For example D3 is about 3-60mm, preferably about 10-40mm, most preferably from about 15-35mm.Aspect one of them, between heating zone and non-heating zone, also has heat insulation of the present utility model.
Another one advantage of the present utility model is, owing to adopted two heating zone in each sample preparation district, can extract biologically active substance particularly last step of nucleic acid (normally wash-out and dissolving nucleic acid step) easily sample is heated, improve the effect of purifying greatly.And because second heating zone and non-heating zone separate, the container ground that the container second heating zone can be independent of non-heating zone takes out, and is convenient to further processing.For example, when using instrument of the present utility model and method to extract biologically active substance (for example nucleic acid), the container (for example centrifuge tube or Eppendorf tube) second heating zone is used for wash-out and dissolving described biologically active substance (for example nucleic acid).These containers (for example centrifuge tube or Eppendorf tube) can independently take out, and are convenient to automatization ground and move further processing such as liquid.And carrying out wash-out and the described biologically active substance of dissolving at same culture plate usually in the prior art, the biologically active substance of Huo Deing is not easy to further processing at last, and need manual sucking-off from this culture plate, or entire plate is operated.
In addition, in the method for extracting biological sample, the volume of liquid in containers that holds sample and reagent is huge to the influence of extraction effect, the setting in two heating work districts at above-mentioned non-heating work of the present utility model district and its two ends, the particularly setting of second heating zone, avoid or significantly reduced the volatilization of the liquid in the container in non-heating work district, guaranteed accuracy and the effect of experiment.
Aspect one of the present utility model, work system of the present utility model is applicable to 24 holes or 96 hole depth orifice plates or PCR microwell plate, for example meets 96 hole on-gauge plates of the parameter of ANSISBS1-42004 standard.24 orifice plates are 4 * 6 types, namely have 6 holes of the 4 every rows of row.24 orifice plate apertures can be about 18mm, and plate is rectangle, and the length of its housing is about 127.76mm ± 0.25mm, and wide is about 85.48mm ± 0.25mm.96 orifice plates are 8 * 12 types, namely have 12 holes of the 8 every rows of row.96 orifice plate apertures can be about 9mm, and plate is rectangle, and the length of its housing is about 127.76mm ± 0.25mm, and wide is about 85.48mm ± 0.25mm.
Work system of the present utility model makes bar magnet method extraction apparatus can be advantageously used in handling single or several samples, also can handle the sample of big flux.
Shown in Fig. 6 a-6c, of the present utility model aspect one of them, at two heating work district 2(heating tanks 64 for example that are fixed on the loading panel described in the sample preparation district 66, being arranged so that between described two heating work districts 65) can 24 holes of horizontal positioned or 96 hole PCR microwell plate or deep-well plates, or place the plate (it has length and the width identical with 24 holes or 96 hole PCR microwell plates or deep-well plates) of centrifuge tube or centrifuge tube connection, the long limit of wherein said PCR microwell plate or deep-well plates or plate (i.e. the orientation in 12 holes of every row of the orientation in 6 holes of every row of 24 orifice plates or 96 orifice plates) is parallel with heating work district (for example heating tank).Preferably, described PCR microwell plate or deep-well plates are arranged between two heating work districts between two parties.Preferably, described PCR microwell plate or deep-well plates are the standard deep plate, for example meet 96 hole on-gauge plates of the parameter of ANSISBS12004 and ANSISBS22004 standard, and the length of its housing is 127.76mm ± 0.25mm, and wide is 85.48mm ± 0.25mm.For satisfy handle sample in heating work district and non-heating zone the zone on workplatform at a distance of certain distance, so that handling the heat of sample generation, the heating work district can not produce effective influence to the sample of handling in non-heating zone, wherein two heating zone (for example heating tank) with near its distance B in the hole that is used for placing container (for example being arranged on the hole of close heating tank of 24 holes of non-heating zone or 96 hole PCR microwell plates or deep-well plates) of non-heating zone greater than 5mm, be preferably greater than 10mm, most preferably greater than 15mm.For example D is about 5-60mm, preferably about 10-40mm, most preferably from about 15-35mm.In an embodiment of the present utility model, two heating work districts that are fixed on the loading panel are heating tank, and the distance B 1 of two heating tanks is preferably greater than 105mm greater than 90mm, most preferably greater than 120mm.For example D1 is about 90-160mm, preferably about 105-150mm, most preferably from about 120-140mm.The distance B 2 at the center of two heating tanks is preferably greater than 120mm greater than 110mm, most preferably greater than 130mm.For example D2 is about 110-200mm, preferably about 115-180mm, most preferably from about 120-160mm.In another preferred implementation of the present utility model, heat insulation is set outside heating tank, heat insulation is the rectangular parallelepiped of hollow, heating tank can embed the hollow space of heat insulation.The thickness of the frame of heat insulation can be arranged so that two distances between the heat insulation are identical with the width of 24 holes that are placed on non-heating work district or 96 hole PCR microwell plates or deep-well plates.In another preferred implementation of the present utility model, the frame of described PCR microwell plate or deep-well plates or plate and its distance B 3 at a distance of nearer heating work district (for example heating tank) are about 5-20mm, are preferably greater than about 5mm, most preferably are greater than about 10mm.
The bar magnet method is extracted biologically active substance, and the method for for example extracting nucleic acid generally includes following steps: a) by sample is contacted with lysate (lysis buffer) and/or Proteinase K, at about 50-60 ℃ of following incubation, cracking biological sample; B) add magnetic bead, before use abundant mixing magnetic bead; C) add in conjunction with liquid (binding buffer), leave standstill; D) use washings I(wash buffer I respectively), cleaning solution II (wash buffer II) and cleaning solution II I(wash buffer III) washing three times; E) with elutriant (elution buffer) wash-out nucleic acid.
When being used for some biomaterial (for example virus) extraction nucleic acid, can join in the lysate in step a) in conjunction with liquid, namely step c) can merge to step a).When being used for some biomaterial (for example virus) extraction nucleic acid, at step b) and d) between have step into nucleic acid settling agent (Acryl Carrier).
Reagent wherein, as lysate (lysis buffer), in conjunction with liquid (binding buffer), washings I-III(wash buffer) and elutriant (elution buffer) can place in advance/seal up for safekeeping in container, also can extract preceding adding.Magnetic bead usually needs carry out the container that holds magnetic bead before use centrifugal, so that the abundant mixing of magnetic bead or concentrate on this container bottom.
Using instrument of the present utility model to extract biologically active substance, when for example extracting nucleic acid, can add biological sample and/or reagent at the container (for example centrifuge tube, deep-well plates etc.) that is placed on the worktable, then by sleeve pipe moving up and down or vibrate in container, can to the reagent in the container and sample stir and mixing, so that sample and reagent fully react.Can make sleeve pipe produce magnetic field outward thus by sleeve pipe and needle are inserted container simultaneously in addition, thereby realize that sleeve pipe is to the absorption of the biological sample of the magnetic bead in the solution in the container or band magnetic bead.When needle left sleeve pipe, the sleeve pipe foreign field disappeared, thereby the biological sample of realizing magnetic bead or band magnetic bead breaks away from sleeve pipe, namely discharges the biological sample of magnetic bead or band magnetic bead.Thus can be mobile in different vessels by sleeve pipe and needle, reach the purpose of the biological sample that shifts magnetic bead or band magnetic bead.
Using instrument of the present utility model to extract biologically active substance, for example extract in the method for nucleic acid, generally include following steps: a) by sample is added the container a that holds lysate (lysis buffer), at about 50-60 ℃ of following incubation; B) by needle and sleeve pipe with magnetic bead from the container b that holds magnetic bead with magnetic bead absorption with transfer to said vesse a, optional, using the centrifugal container that holds magnetic bead; C) optional, by needle and sleeve pipe with the magnetic bead among the container a or in conjunction with the sample absorption of magnetic bead with transfer to the container c that holds in conjunction with liquid (binding buffer); D) adsorb successively and transfer to and hold washings I(wash buffer I with above-mentioned magnetic bead or in conjunction with the sample of magnetic bead), cleaning solution II (wash buffer II) and cleaning solution II I(wash buffer III) container d1, container d2 and container d3; E) will be through the magnetic bead in the step d) or in conjunction with the absorption of the sample of magnetic bead with transfer to the container e that holds elutriant (elution buffer), about 50-60 ℃ of following incubation.When being used for some biomaterial (for example virus) extraction nucleic acid, can join in the lysate in step a) in conjunction with liquid, namely step c) can merge to step a).Be used for some biomaterial (for example virus) when extracting nucleic acid, step b) and d) between have magnetic bead or adsorb and transfer to the step of the container that holds nucleic acid settling agent (Acryl Carrier) in conjunction with the sample of magnetic bead.
Extract by the bar magnet method in the instrument and method of nucleic acid at wherein a kind of instrument of the present utility model or work system of utilizing of the present utility model, it is for the treatment of the sample of big flux.
Shown in Fig. 6 a, aspect one of them, in the aforementioned work system of the present utility model, the loading panel has two sample preparation districts 66 of the present utility model, fixedly there is distance B 1 about 120-140mmm of two heating tanks 64 and 65, two heating tanks at the two ends, the left and right sides in each sample preparation district.Distance B 2 about 130-150mm at the center of two heating tanks.Each heating tank has 6 slotted eyes, is horizontally disposed with 24 hole depth orifice plates 83 between two parties in the middle of described two heating tanks.The long limit of wherein said deep-well plates (i.e. the orientation in 6 holes of every row of 24 hole depth orifice plates) is parallel with heating tank, 6 slotted eyes of each heating tank respectively with 6 horizontally-arrangeds (being the row in 4 holes of every row) of 24 hole standard deep plates point-blank.Deep-well plates can be arranged between two heating tanks between two parties.Heating tank has heat insulation 81 outward, and heat insulation is the rectangular parallelepiped of hollow, and heating tank embeds the hollow space of heat insulation.The thickness of the frame of heat insulation is set to equate that with the long limit of 24 hole depth orifice plates and the distance between the heating tank namely the distance B between the heat insulation of two heating tanks 2 is identical with the width of described 24 hole depth orifice plates.The both sides up and down of 24 hole depth orifice plates are arranged on fixed block 82 restrictions on the loading panel.Slotted eye at heating tank can be placed centrifuge tube, and described centrifuge tube can be cylindrical.Described centrifuge tube aperture can be same or similar with the aperture in described standard 24 holes.Originally the work system of stating utility model before employing extracts in the method for nucleic acid by the bar magnet method, can hold lysate at the centrifuge tube of heating tank one; In 3 vertical setting of types (being the row in 6 holes of every row) of 24 hole depth orifice plates, can hold washings I, cleaning solution II and cleaning solution II I successively; Choose wantonly, can also in a vertical setting of types of 24 hole depth orifice plates, hold magnetic bead or in conjunction with liquid or nucleic acid settling agent; And hold elutriant at the centrifuge tube of heating tank two.The temperature of the reagent of heating tank one can be made as about 50-60 ℃, and the temperature of the reagent of heating tank two can be made as about 50-60 ℃.Corresponding, adopt on two supported arms of the bar magnet of biologically active substance extraction apparatus of above-mentioned work system of the present utility model and cannula system and respectively assemble 6 cover bar magnet and sleeve pipes.In aforesaid method, can at first sample be added the centrifuge tube (centrifuge tube that namely holds lysate) of heating tank one.Under time variable control, bar magnet and/or sleeve pipe insert successively and leave in the container that holds lysate, washings I, cleaning solution II, cleaning solution II I and elutriant, finish for example extraction of nucleic acid of biologically active substance.Can also comprise the step of inserting and leaving the container that holds magnetic bead in bar magnet and/or sleeve pipe insertion with before leaving the container that holds lysate.Can also comprise insertion and leave the step of holding in conjunction with the container of liquid in bar magnet and/or sleeve pipe insertion with before leaving the container that holds washings I.
Aspect one of the present utility model, the above-mentioned hole that holds reagent can seal, i.e. aforementioned agents is held in sealing.Preferably, aforementioned 24 hole depth orifice plates are the 24 hole standard deep culture plates that meet the parameter of ANSISBS standard, and the length of its housing is 127.76mm ± 0.25mm, and wide is 85.48mm ± 0.25mm, and the aperture is about 18mm.Aspect one of the present utility model, the slotted eye of described heating tank is suitable for inserting the aperture and is the centrifuge tube of about 18mm.Aspect one of the present utility model, described centrifuge tube and heating tank to be arranged so that centrifuge tube inserts its mouth of pipe behind the slotted eye same or similar apart from the height of the height of loading panel upper surface and described deep-well plates, namely make the mouth of pipe height of centrifuge tube and the upper surface basic horizontal of deep-well plates.
Shown in Fig. 6 b, aspect one of them, in the aforementioned work system of the present utility model, the loading panel has two sample preparation districts 66 of the present utility model, fixedly there is distance B 1 about 120-140mmm of two heating tanks 64 and 65, two heating tanks at the two ends, the left and right sides in each sample preparation district.Distance B 2 about 130-150mm at the center of two heating tanks.Each heating tank has 12 slotted eyes, is horizontally disposed with 96 hole depth orifice plates 84 between two parties in the middle of described two heating tanks.The long limit of wherein said deep-well plates (i.e. the orientation in 12 holes of every row of 96 hole depth orifice plates) is parallel with heating tank, 12 slotted eyes of each heating tank respectively with 12 horizontally-arrangeds (being the row in 8 holes of every row) of 96 hole depth orifice plates point-blank.Deep-well plates can be arranged between two heating tanks between two parties.Heating tank has heat insulation 81 outward, and heat insulation is the rectangular parallelepiped of hollow, and heating tank embeds the hollow space of heat insulation.The thickness of the frame of heat insulation is set to equate that with the long limit of 96 hole depth orifice plates and the distance between the heating tank namely the distance between the heat insulation of two heating tanks is identical with the width of described 96 hole depth orifice plates.The both sides up and down of 96 hole depth orifice plates are arranged on fixed block 82 restrictions on the loading panel.Slotted eye at heating tank can be placed centrifuge tube, and described centrifuge tube is cylindrical.The aperture can be same or similar with the aperture in described standard 96 holes.Originally the work system of stating utility model before employing extracts in the method for nucleic acid by the bar magnet method, can hold lysate at the centrifuge tube of heating tank one; In 3 vertical setting of types (being the row in 12 holes of every row) of 96 hole depth orifice plates, can hold washings I, cleaning solution II and cleaning solution II I successively; Choose wantonly, can also in the vertical setting of types of 96 hole depth orifice plates, hold magnetic bead and/or in conjunction with liquid and/or nucleic acid settling agent; And hold elutriant at the centrifuge tube of heating tank two.The temperature of the reagent of heating tank one can be made as about 50-60 ℃, and the temperature of the reagent of heating tank two can be made as about 50-60 ℃.Corresponding, adopt on two supported arms of the bar magnet of biologically active substance extraction apparatus of above-mentioned work system of the present utility model and cannula system and respectively assemble 12 cover bar magnet and sleeve pipes.In aforesaid method, can at first sample be added the centrifuge tube (centrifuge tube that namely holds lysate) of heating tank one.Under time variable control, bar magnet and sleeve pipe insert successively and leave in the container that holds lysate, washings I, cleaning solution II, cleaning solution II I and elutriant, finish for example extraction of nucleic acid of biologically active substance.Can also comprise the step of inserting and leaving the container that holds magnetic bead in bar magnet and/or sleeve pipe insertion with before leaving the container that holds lysate.Can also comprise insertion and leave the step of holding in conjunction with the container of liquid in bar magnet and/or sleeve pipe insertion with before leaving the container that holds washings I.Can also comprise the step of inserting and leaving the container that holds the nucleic acid settling agent in bar magnet and/or sleeve pipe insertion with before leaving the container that holds washings I.
Aspect one of the present utility model, the above-mentioned hole that holds reagent can seal, i.e. aforementioned agents is held in sealing.Preferably, aforementioned 96 hole depth orifice plates are the 96 hole standard deep culture plates that meet the parameter of ANSISBS standard, and the length of its housing is 127.76mm ± 0.25mm, and wide is 85.48mm ± 0.25mm, and the aperture is about 9mm.Aspect one of the present utility model, the slotted eye of described heating tank is suitable for inserting the aperture and is the centrifuge tube of about 9mm.Aspect one of the present utility model, described centrifuge tube and heating tank to be arranged so that centrifuge tube inserts its mouth of pipe behind the slotted eye same or similar apart from the height of the height of loading panel upper surface and described deep-well plates, namely make the mouth of pipe height of centrifuge tube and the upper surface basic horizontal of deep-well plates.
Above-mentioned equipment of the present utility model and method also can be for the treatment of single or several samples.
Wherein a kind of the utilization in the method for work system of the present utility model by bar magnet method extraction nucleic acid of the present utility model, its work embodiment is for the treatment of single or a few sample (be generally and be less than 6).
Shown in Fig. 6 c, aspect one of them, adopt work system of the present utility model and method to handle 1 to 5 sample of the present utility model.Corresponding, in aforementioned work system of the present utility model, the loading panel has two sample preparation districts, and fixedly there is distance B 1 about 120-140mmm of two heating tanks 64 and 65, two heating tanks at the two ends in each sample preparation district.Distance B 2 about 130-150mm at the center of two heating tanks.Each heating tank has 5 slotted eyes.One to five tetrad pipe 86 is set between described two heating tanks, 4 centrifuge tubes are arranged on the described tetrad pipe.4 centrifuge tubes of each tetrad pipe and the corresponding slotted eye of two heating tanks are point-blank.Described tetrad pipe can be fixed on the centrifuge tube shelf 85 that is placed on the loading panel.Described centrifuge tube shelf 85 can be to have for the groove of described one or more tetrad pipes insertions or the flat board in hole.Preferably, described centrifuge tube shelf has length and the width same with 96 hole standard deep culture plates of the parameter that meets ANSISBS12004 and ANSISBS22004 standard, and namely long is 127.76mm ± 0.25mm, and wide is 85.48mm ± 0.25mm.Thus, the fixed block 82 that is applicable to fixing described standard deep culture plate in the side setting of the front and back in non-heating work district also can be used for fixing described centrifuge tube shelf.Described tetrad pipe also can be fixed in the groove or hole of loading panel.Can have heat insulation outside the heating tank two, heat insulation is the rectangular parallelepiped of hollow, and heating tank embeds the hollow space of heat insulation.The thickness of the frame of heat insulation can be set to the centrifuge tube shelf of placing described tetrad pipe and heating tank between distance equate.Slotted eye at heating tank can be placed centrifuge tube, and described centrifuge tube is cylindrical, and the aperture can be similar to the aperture of described tetrad pipe.In addition, between each slotted eye of heating tank one and corresponding tetrad pipe a magnetic bead centrifuge tube 87 can be set also, it can be used for encapsulating magnetic bead.The magnetic bead centrifuge tube can take out easily, in order to shook before in advance the step of biologically active substance begins and/or centrifugal, reaches before the reaction the fully purpose of mixing magnetic bead.Described magnetic bead centrifuge tube can be fixed on aforementioned for the fixing centrifuge tube shelf of tetrad pipe, also can be fixed in the groove or hole of loading panel.
Originally the work system of stating utility model before employing extracts in the method for nucleic acid by the bar magnet method, can hold lysate at the centrifuge tube of heating tank one; 3 Kong Zhongke at the tetrad pipe hold washings I, cleaning solution II and cleaning solution II I successively; Choose wantonly, can also in a hole of tetrad pipe, hold in conjunction with liquid and/or nucleic acid settling agent; And hold elutriant at the centrifuge tube of heating tank two.Choose wantonly, can also in described magnetic bead centrifuge tube, hold magnetic bead.The temperature of the reagent of heating tank one can be made as about 50-60 ℃, and the temperature of the reagent of heating tank two can be made as about 50-60 ℃.Corresponding, adopt on two supported arms of the bar magnet of biologically active substance extraction apparatus of above-mentioned work system of the present utility model and cannula system and respectively assemble 1 to 5 cover bar magnet and sleeve pipe.In aforesaid method, can at first sample be added the centrifuge tube (centrifuge tube that namely holds lysate) of heating tank one.Under time variable control, bar magnet and sleeve pipe insert successively and leave in the container that holds lysate, washings I, cleaning solution II, cleaning solution II I and elutriant, finish for example extraction of nucleic acid of biologically active substance.Can also comprise the step of inserting and leaving the magnetic bead centrifuge tube in bar magnet and/or sleeve pipe insertion with before leaving the container that holds lysate.Can also comprise the step that the magnetic bead centrifuge tube is centrifugal in bar magnet and/or sleeve pipe insertion with before leaving the magnetic bead centrifuge tube.Can also comprise insertion and leave the step of holding in conjunction with the container of liquid in bar magnet and/or sleeve pipe insertion with before leaving the container that holds washings I.Can also comprise the step of inserting and leaving the container that holds the nucleic acid settling agent in bar magnet and/or sleeve pipe insertion with before leaving the container that holds washings I.The temperature of the reagent of heating tank one can be made as about 50-60 ℃, and the temperature of the reagent of heating tank two can be made as about 50-60 ℃.
Aspect one of the present utility model, the above-mentioned hole that holds reagent can seal, i.e. aforementioned agents is held in sealing.
Of the present utility model aspect one of them, the centrifuge tube shelf of described tetrad pipe and fixing described tetrad pipe or the groove of loading panel or hole be arranged so that the tetrad pipe mouth of pipe is same or similar apart from the height of the height of loading panel upper surface and aforesaid standards deep-well plates, namely make upper surface basic horizontal when the mouth of pipe height of centrifuge tube of tetrad pipe and standard deep plate level place the loading panel.Of the present utility model aspect another, between each slotted eye of heating tank one and corresponding tetrad pipe, a magnetic bead centrifuge tube is set also, the aperture of described magnetic bead centrifuge tube and tetrad pipe same or similar.Preferably, the centrifuge tube shelf of described magnetic bead centrifuge tube and fixing described magnetic bead centrifuge tube or the groove of loading panel or hole be arranged so that the magnetic bead centrifuge tube mouth of pipe is same or similar apart from the height of the height of loading panel upper surface and aforesaid standards deep-well plates, namely make upper surface basic horizontal when the mouth of pipe height of magnetic bead centrifuge tube and standard deep plate level place the loading panel.
Of the present utility model aspect one of them, in aforementioned work system of the present utility model, at the slotted eye of heating tank one lysate centrifuge tube 88 is set.Slotted eye at heating tank two arranges elutriant centrifuge tube 89.Between each slotted eye of heating tank one and corresponding tetrad pipe a magnetic bead centrifuge tube 87 can be set also, it can be used for encapsulating magnetic bead.The magnetic bead centrifuge tube can take out easily, in order to shook before in advance the step of biologically active substance begins and/or centrifugal, reaches before the reaction the fully purpose of mixing magnetic bead.
Originally the work system of stating utility model before employing extracts in the method for nucleic acid by the bar magnet method, can hold lysate at the lysate centrifuge tube of heating tank one; 3 Kong Zhongke at the tetrad pipe hold washings I, cleaning solution II and cleaning solution II I successively; Choose wantonly, can also in a hole of tetrad pipe, hold in conjunction with liquid and/or nucleic acid settling agent; And hold elutriant at the wash-out centrifuge tube of heating tank two.Choose wantonly, can also in described magnetic bead centrifuge tube, hold magnetic bead.The temperature of the reagent of heating tank one can be made as about 50-60 ℃, and the temperature of the reagent of heating tank two can be made as about 50-60 ℃.
Corresponding, adopt on two supported arms of the bar magnet of biologically active substance extraction apparatus of above-mentioned work system of the present utility model and cannula system and respectively assemble 1 to 5 cover bar magnet and sleeve pipe.In aforesaid method, can at first sample be added the lysate centrifuge tube of heating tank one.Under time variable control, bar magnet and sleeve pipe insert successively and leave in the container that holds lysate, washings I, cleaning solution II, cleaning solution II I and elutriant, finish for example extraction of nucleic acid of biologically active substance.Can also comprise the step of inserting and leaving the magnetic bead centrifuge tube in bar magnet and/or sleeve pipe insertion with before leaving the container that holds lysate.Can also comprise the step that the magnetic bead centrifuge tube is centrifugal in bar magnet and/or sleeve pipe insertion with before leaving the magnetic bead centrifuge tube.Can also comprise insertion and leave the step of holding in conjunction with the container of liquid in bar magnet and/or sleeve pipe insertion with before leaving the container that holds washings I.Can also comprise the step of inserting and leaving the container that holds the nucleic acid settling agent in bar magnet and/or sleeve pipe insertion with before leaving the container that holds washings I.
The design of work system of the present utility model makes the automatization of nucleic acid extraction instrument further improve, and can be suitable for various type culture plates simultaneously, and the needs that can be used for indivedual or big flux nucleic acid extraction simultaneously.
Instrument of the present utility model also can have local air flow and produce system.Produce the microenvironment that local air flow improves bar magnet method extraction biologically active substance by adopting, thereby effectively reduce the pollution that aerosol causes when the bar magnet method is extracted.In the biologically active substance extraction apparatus that adopts the bar magnet method, sleeve pipe contacts with liquid in the container that holds sample or reagent, has an opportunity to generate aerosol.In the utility model, described microenvironment preferred disposition produces the local air flow of horizontal flow for the upper area that upwards is placed on the opening of the container in the sample preparation district at biologically active substance extraction apparatus split shed, the aerosol that makes sleeve pipe contact with liquid in the container to produce moves horizontally after vessel port discharges, thereby the aerosol that prevents from having biological sample floats to and causes in other container polluting.Method of the present utility model and instrument are specially adapted to extract nucleic acid.
Shown in Fig. 3 and 4, two perforates that side plate has horizontal symmetrical of tool housing of the present utility model form the gas channel that air-flow produces system.The height of perforate setting makes the air-flow by the horizontal flow of these two perforates can upwards be placed on the upper area of the opening of the container in the sample preparation district by opening.The height that can determine perforate according to container and the modes of emplacement of described container in the sample preparation district of employing.The top of the container on the height of perforate can be set to aperture bottom and be placed on the sample preparation district is identical or a little less than described top.For the various containers of compatibility, the top of the container that the height on the height of perforate can be set to aperture bottom and be placed on the sample preparation district is minimum is identical or a little less than described top.Aspect one of the present utility model, the bottom of perforate is than the high about 0-50mm of upper surface of loading panel, preferred 3-15mm, most preferably from about 5-10mm.
Aspect one of the present utility model, the non-heating work district on the loading panel is used for the PCR microwell plate is set, and described PCR microwell plate can lie on the loading panel, and it highly is generally about 10-20mm, preferably about 13-16mm.In a utility model of the present utility model, the non-heating work district on the loading panel is used for deep-well plates is set, and described deep-well plates can lie on the loading panel, and it highly is generally about 30-50mm, preferred 38-45mm, most preferably from about 40-43mm.In addition, the heating work district on the loading panel is heating tank, and the container of placing in heating tank is centrifuge tube or Eppendorf tube, is placed in the slotted eye of heating tank.Described centrifuge tube and heating tank to be arranged so that centrifuge tube inserts its mouth of pipe behind the slotted eye same or similar apart from the height of the height of loading panel upper surface and described PCR microwell plate or deep-well plates, namely make the mouth of pipe height of centrifuge tube and the upper surface basic horizontal of described PCR microwell plate or deep-well plates.For example, in the utility model embodiment as shown in the figure, heating tank is than the about 10mm of loading surface plate hight, if the container of non-heating zone is the PCR microwell plate, then be placed on the centrifuge tube top of heating tank than the high about 1-10mm in heating tank top, preferably about 3-6mm most preferably is 4.35mm ± 0.76mm.If the container of non-heating zone is plate hight is the deep-well plates of 30-50mm, then be placed on the centrifuge tube top of heating tank than the high about 20-40mm in heating tank top.For the various containers of compatibility, the top of the container that the height on the height of perforate can be set to aperture bottom and be placed on the sample preparation district is minimum is identical or a little less than described top.Thus, the bottom of perforate can be set than the high about 0-15mm of upper surface of loading panel, preferred 3-15mm, most preferably from about 5-10mm.
Perforate can be pore district 56.Pore district 56 can be rectangle.The length in rectangle pore district (being the horizontal length in pore district) adapts with the container that is placed in the sample preparation district.In wherein a kind of embodiment of the present utility model, it is identical or close with the length of supported arm that the length in rectangle pore district is set to.In wherein a kind of embodiment of the present utility model, the length in rectangle pore district is set to equate with the long limit of 24 orifice plates or 96 orifice plates (the 96 hole on-gauge plates that for example meet the parameter of ANSISBS12004 and ANSISBS22004 standard) or greater than described long limit, preferably, the length in described rectangle pore district is greater than about 127.76mm, for example be about 127-140mm, be preferably about 128-135mm.The width in rectangle pore district (being the vertical length in described pore district) is suitable for forming the local air flow of horizontal flow, and can take into account the height that is placed on the container in the sample preparation district of various height.In wherein a kind of embodiment of the present utility model, the width in rectangle pore district is set to about 30-80mm, is preferably about 40-70mm, most preferably is about 50-65mm.The height of the distance from bottom loading panel upper surface in rectangle pore district is identical with the top of container on being placed on the sample preparation district or a little less than described top.For example, the bottom of aperture area is set than the about 5-15mm of loading surface plate hight, preferred 5-10mm.
In other embodiment of the present utility model, can be by the height that perforate is adjusted in perforate moving up and down be set at side plate, make the air-flow of the horizontal flow by these two perforates can upwards be placed on the upper area of the opening of the container in the sample preparation district by opening.
In other embodiment of the present utility model, can be by Work platform system moving up and down be set, make the loading panel can adjust height, make that the upper area of the opening be placed on the container in the sample preparation district is same or similar with the level attitude by two perforates.
In wherein a kind of embodiment of the present utility model, side plate 73 comprises outer panel 731 and interior plate 732.
Can offer round hole at outer panel, be suitable for installing fan.
The perforate of interior plate is rectangle pore district 56.The length in rectangle pore district (being the horizontal length in pore district) adapts with the container that is placed in the sample preparation district.In wherein a kind of embodiment of the present utility model, the length in rectangle pore district is set to equate with the long limit of 24 orifice plates or 96 orifice plates (the 96 hole on-gauge plates that for example meet the parameter of ANSISBS12004 and ANSISBS22004 standard) or greater than described long limit, for example be about 127-140mm, be preferably about 128-135mm.The width in rectangle pore district is set to 40-70mm, most preferably is about 50-65mm.The height of the distance from bottom loading panel upper surface in rectangle pore district is identical with the top of container on being placed on the sample preparation district or a little less than described top.In the utility model embodiment as shown in the figure, the bottom of perforate is set than the high about 0-15mm of upper surface of loading panel, preferred 3-10mm, most preferably 5-10mm.
In another kind of embodiment of the present utility model, at the arranged outside conduit (not shown on the figure) of tool housing side plate perforate.The outer fringe seal of the perforate on one end of described conduit and the outer panel is connected, and the other end is connected with specified location.In a kind of embodiment of the present utility model, an end that connects the conduit of the perforate of giving vent to anger is connected with described perforate, the other end opening is arranged on the designated area, for example with interatrial septum, instrument place from the room, can only enter the designated area along conduit from the instrument internal effluent air, guarantee thus in the instrument biological substance for example nucleic acid can not pollute room, instrument place.In a kind of embodiment of the present utility model, one end of the conduit of the perforate of connection air inlet is connected with described perforate, the other end opening in interatrial septum, instrument place from the room or the zone of pollution-free gas is provided, thus, the gas that guarantees to enter instrument internal or room, instrument place thus is not subjected to the pollution of other biological substance.
Illustrate in two perforates of shell outer panel of instrument of the present utility model fan all is set.Fan is placed in the perforate of outer panel.One of them fan is supply fan 50, is placed in the perforate of outer panel 731, and interior plate arranges pore 56.The air-flow that supply fan 50 produces is for to enter instrument internal from the instrument outside.Another fan is extraction fan 53, and the air-flow of generation is for to enter the instrument outside from instrument internal.Fan is set to produce the air-flow of horizontal flow.
In another embodiment of the present utility model, can have only supply fan or extraction fan.
The air flow source that the air-flow of the utility model instrument produces system also can be for draught head produces system, for example the mechanism of the generation negative pressure of setting the perforate of giving vent to anger outside.
Illustrate in the instrument of the present utility model, at the arranged outside filter screen grid 1 of supply fan 50, filter screen grid one 51 arranged outside net filter bowls 1.In addition, at the arranged outside filter screen grid 2 54 of the fan 53 of giving vent to anger, filter screen grid 2 54 arranged outside net filter bowls 2 55.The filter screen grid that the utility model adopts can be biochemical filtering net, filter cotton, biochemical felt, plastic filtering net etc.The size of mesh of the filter screen grid that the utility model adopts is generally more than or equal to 0.045mm.The filter screen order number of described filter screen grid is for being less than or equal to 325 orders.The filter screen order is counted General Definition and is referred in the area of 1 inch of 1 inch * what mesh count are arranged, i.e. the mesh count of screen cloth, and how many order numbers material can namely be defined as by this mesh.As 200 orders, be exactly that this material can be by there being the screen cloth of 200 mesh in 1 inch of 1 inch *.Filter screen grid one can prevent that the outside air filtered from entering instrument, and the gas of avoiding entering instrument internal or room, instrument place is subjected to the pollution of dust and/or other biological substance.Filter screen grid two can prevent that the air filtered is overflowed instrument in the instrument, also can prevent from the gas in room, instrument place is polluted.
The level that air-flow generation system produces in the utility model is about 0.3-0.8 meter per second by the speed of the local air flow of the upper area of the opening of sample preparation district upper container, preferably about 0.4-0.7 meter per second, most preferably from about 0.45-0.5 meter per second.
In the biologically active substance extraction apparatus that adopts the bar magnet method, sleeve pipe contacts with liquid in the container that holds sample or reagent, has an opportunity to generate the aerosol that has biological sample.Sample in the container on described local air flow helps to prevent sleeve pipe and be placed on the sample preparation district or reagent (being generally liquid) contacts the aerosol that produces and float to behind overflow container and cause pollution in other container.
Using instrument of the present utility model to extract biologically active substance, when for example extracting nucleic acid, thereby comprise the container internal vibration on being placed on the sample preparation district of sleeve pipe and/or needle to the reagent in the container and/or sample stirs and mixing, so that the step that sample and reagent fully react.Aspect one of the present utility model, at sleeve pipe and/or needle during in the container internal vibration, produce the local air flow that system upwards is placed on the opening of the container in the sample preparation district at opening upper area produces horizontal flow by above-mentioned local air flow.Use instrument of the present utility model to extract biologically active substance, when for example extracting nucleic acid, comprising that sleeve pipe and/or needle raise and leave the container that is placed in the sample preparation district, thereby realizing shifting magnetic bead or in conjunction with the step of the biological substance of magnetic bead.Aspect one of the present utility model, when sleeve pipe and/or needle raise and leave the container that is placed in the sample preparation district, above-mentioned local air flow generation system stopped to produce the air-flow of horizontal flow.
In the utility model, described air-flow produces system and also has Controlling System, the generation that is used for the described local air flow of control whether with the speed of the air-flow that produces.An aspect at this aspect when described Controlling System can and be left the container that is placed in the sample preparation district in sleeve pipe and/or needle rising, makes local air flow generation system stop to produce the air-flow of horizontal flow.At another aspect of this aspect, described Controlling System can be controlled air flow source, fan for example, the speed of the air-flow of generation.
As shown in the figure, described have needle 7 and needle travel mechanism 48 for the instrument that extracts biologically active substance.Needle travel mechanism 48 comprises needle support 8 and needle rising mechanism 33.
Needle support 8 comprises needle support end block 9 and needle supported arm 34.Needle removably is fixed on the needle supported arm.At the instrument that is used for extracting biologically active substance of diagram preferred embodiment of the present utility model, the needle support has two needle supported arms that be arranged in parallel.The needle support also can have only a needle supported arm, also can be above two.The quantity of the fixable needle of each needle supported arm can be adjusted as required, and common every group is 1-12 root needle, and common is 4,6 or 12 needles.At another embodiment, the needle supported arm is the needle group fixedly, and each needle group has many row's needles, 24 of corresponding culture plate needles (spread pattern is 4 * 6) for example, 96 needles (spread pattern is 8 * 12) etc.In the present embodiment, the bottom of needle has permanent magnet, has magnetic thus.In other embodiment of the present utility model, needle also can produce magnetic by electromagnetic action.
Needle rising mechanism comprises that needle promotes end block 17, motor 12, and leading screw 2 32 and nut transmission pair, motor drives promotion end block 17 by leading screw and nut transmission pair and moves upward.Needle promotes end block 17 and is arranged on needle support end block 9 belows.Needle promotes end block and can contact with needle support end block.When motor drives when promoting end block and moving upward by leading screw and nut transmission pair, needle promotes end block and contact with needle support end block, and promotion needle support end block moves upward, thereby promotion needle support moves upward.
Described also have sleeve pipe 4 and sleeve pipe travel mechanism 16 for the instrument that extracts biologically active substance.Sleeve pipe travel mechanism comprises casing support 6 and sleeve pipe hoisting appliance 18.Casing support comprises casing support end block 35 and casing support arm 5.At the instrument that is used for extracting biologically active substance of diagram preferred embodiment of the present utility model, casing support has two casing support arms that be arranged in parallel.Casing support also can have only a casing support arm, also can be above two.Sleeve pipe removably is fixed on the casing support arm.The quantity of the fixable sleeve pipe of each casing support arm can be adjusted as required.The quantity of sleeve pipe can be adjusted as required, and common every group is 1-12 root sleeve pipe.Common is 4,6 or 12 sleeve pipes.At another embodiment, but casing support arm fixed sleeving group, and each sleeve pipe group has many bar casing tubes, 24 of corresponding culture plate sleeve pipes (spread pattern is 4 * 6) for example, 96 sleeve pipes (spread pattern is 8 * 12) etc.
The sleeve pipe hoisting appliance comprises sleeve pipe lifting end block 36, motor 11, leading screw 1 and nut transmission pair.Motor drives sleeve pipe lifting end block by leading screw and nut transmission pair and moves up or down.Sleeve pipe lifting end block is arranged on casing support end block below.Sleeve pipe lifting end block can with the contacting of casing support end block.When motor drove sleeve pipe lifting end block and moves upward by leading screw and nut transmission pair, sleeve pipe lifting end block can contact with the casing support end block, and promoted the casing support end block and move upward, thereby the promotion casing support moves upward.When motor moved downward by leading screw and nut transmission pair drive sleeve pipe lifting end block, the casing support end block moved downward synchronously according to action of gravity and sleeve pipe lifting end block, moves downward thereby drive casing support.
Sleeve pipe lifting end block 36 is separable with casing support end block 35, the vibration that realizes sleeve pipe thus with move up and down and can be controlled by different institutions independently.
Sleeve pipe lifting end block is arranged at casing support end block 35 belows.When motor moves upward by leading screw and nut transmission pair drive sleeve pipe lifting end block, promote casing support and move upward.When motor moved downward by leading screw and nut transmission pair drive sleeve pipe lifting end block, the casing support end block moved downward synchronously according to action of gravity and sleeve pipe lifting end block, moves downward thereby drive casing support.
At the instrument that is used for extracting biologically active substance of diagram preferred embodiment of the present utility model, casing support end block below arranges cover tube vibration push rod 26, and it is connected with vibrating mechanism, conduction vibration.
The instrument that is used for extracting biologically active substance at diagram preferred embodiment of the present utility model, sleeve pipe lifting end block is arranged on casing support end block below, the length of its upper surface is identical with the lower surface of casing support end block with width, can rise sleeve pipe lifting end block and support and pushing effect.In the middle of sleeve pipe lifting end block, has cavity.Cover tube vibration push rod also is arranged on casing support end block below, and its upper surface length is littler than the lower surface of casing support end block with width.Have cavity in the middle of sleeve pipe lifting end block, can allow cover tube vibration push rod pass, the upper end of cover tube vibration push rod contacts with the casing support end block, and the lower end contacts with the vibrating mechanism that is arranged on sleeve pipe travel mechanism below.
Aspect one of the present utility model, it is separable with needle support end block 9 that needle promotes end block 17.Needle promotes a side contacts of end block and needle support end block.When motor moves upward by leading screw and nut transmission pair drive promotion end block, promote the needle support by needle support end block and move upward.Needle is upwards broken away from from sleeve pipe.Moving downward of needle support is according to action of gravity.The needle of instrument of the present utility model promotes end block and the needle support is separable, and this design can realize that the needle termination contacts closely with the abundant of sleeve bottom, has simplified the requirement to automatically controlled part, prevents that needle from impacting the phenomenon generation of sleeve bottom.
Fig. 7 a illustrates the working order of described instrument when needle inserts sleeve pipe.Needle 4 inserts sleeve pipe, and its bottom contacts with the bottom of sleeve pipe.Needle promotion this moment end block 17 separates with needle support end block 9, and needle support 8 is supported by casing support 6 and together moves with casing support.Another kind of embodiment is that needle 4 inserts sleeve pipes, arrives predeterminedly near the position of the bottom of sleeve pipe, and needle promoted end block 17 and separated with needle support end block 9 this moment, and the needle support is supported by casing support and together moves with casing support.Predetermined needle bottom arrive near the position of sleeve bottom can by casing support 6 and needle support 8 arrange limit, for example be set to needle supported arm and casing support arm contact, or the male member that arranges on needle supported arm and the casing support arm contacts, and described male member can be the cushioning material preparation.
Fig. 7 b illustrates the working order that sleeve pipe separates with needle.Needle promotes a side contacts of end block 17 and needle support end block 9.When motor moves upward by leading screw and nut transmission pair drive needle promotion end block, promote the needle support by needle support end block and move upward, needle separates with sleeve pipe.
In addition, sleeve pipe lifting end block 35 contacts with casing support end block 36, when motor moves upward by leading screw and nut transmission pair drive sleeve pipe lifting end block, promotes casing support and moves upward.When motor moved downward by leading screw and nut transmission pair drive sleeve pipe lifting end block, casing support moved downward with sleeve pipe lifting end block under action of gravity.
Thereby when the biological sample of the magnetic bead that needs sleeve pipe by vibrating outside the wash-out sleeve pipe absorption or band magnetic bead, needle support end block promotes the needle support and moves upward, and sleeve pipe separates with needle.Sleeve pipe lifting end block and casing support end block disengage.Casing support vibrates under the vibrating mechanism effect.
When needing sleeve pipe to insert or during the hole of the centrifuge tube of sample area or deep-well plates, sleeve pipe lifting end block 35 contacts with casing support end block 36, when motor moved upward by leading screw and nut transmission pair drive sleeve pipe lifting end block, the promotion casing support moved upward and leaves sample area.When motor moved downward by leading screw and nut transmission pair drive sleeve pipe lifting end block, casing support moved downward with sleeve pipe lifting end block under action of gravity, inserts sample area.
In addition, as shown in the figure, described needle travel mechanism and sleeve pipe travel mechanism are arranged on mechanism's platform 14, are supported by mechanism rack 13.
The both sides of needle support end block 9, sleeve pipe lifting end block 36 and casing support end block 35 have perforation, article two, vertically be arranged on the perforation that the optical axis 10 on mechanism's platform passes described needle support end block 9, sleeve pipe lifting end block 36 and casing support end block 35, needle support end block, sleeve pipe lifting end block and casing support end block worked limiting and fixed action.The both sides that needle promotes end block also have perforation, are passed by other two optical axises.
Of the present utility model have vibrating mechanism for the instrument that extracts biologically active substance, and described vibrating mechanism can produce vibration, makes sleeve pipe travel mechanism drive sleeve pipe and carry out up-down vibration.The sleeve pipe of the instrument of extraction biologically active substance of the present utility model can carry out up-down vibration up to the frequency of 20Hz.As shown in Figure 8, driving mechanism of the present utility model comprises linear lever arm 22, traversing carriage 23, mobile fulcrum shaft 37, drive the driving mechanism 24 that traversing carriage moves horizontally, contact and the vibrating wheels 25 of conduction vibration with the cover tube vibration push rod 26 of sleeve pipe hoisting appliance, and eccentric wheel 21 and eccentric wheel drive-motor 20.Lever arm is linear pattern, has the hollow groove parallel with lower edge with its upper limb.Mobile fulcrum shaft passes hollow groove, can be mobile in hollow groove along the lever arm direction under the traversing carriage driving mechanism drives, form the mobile fulcrum of lever.Contact and the vibrating wheels 25 of conduction vibration and the both sides that eccentric wheel lays respectively at mobile fulcrum with the cover tube vibration push rod 26 of sleeve pipe hoisting appliance.Eccentric wheel contacts with lever arm, when eccentric wheel rotates, cause that the lever arm (power arm) in eccentric wheel one side of fulcrum is subjected to displacement, the lever arm of the opposite side of fulcrum (resistance arm) and vibrating wheels are then carried out rightabout displacement synchronously, and namely the rotation around fulcrum takes place lever arm.Eccentric rotation makes vibrating wheels vibrate, and carries out up-down vibration thereby make sleeve pipe travel mechanism drive sleeve pipe.Also namely, the vibrating mechanism for the instrument that extracts biologically active substance of the present utility model produces vibration, the speed of controlled frequency by eccentric stiffener (being eccentric wheel among the embodiment).The size of the controlled damping width of cloth of movement of the position of mobile fulcrum on lever arm also can be controlled the size of amplitude together with eccentric rotating manner.
Though describe in detail about example embodiment of the present utility model and advantage thereof; be to be understood that under the situation of the protection domain that does not break away from the restriction of spirit of the present utility model and claims, can carry out various variations, substitutions and modifications to these embodiment.For other examples, when those of ordinary skill in the art should understand easily in keeping the utility model protection domain, the order of processing step can change.
In addition, range of application of the present utility model is not limited to technology, mechanism, manufacturing, material composition, means, method and the step of the specific embodiment of describing in the specification sheets.From disclosure of the present utility model, to easily understand as those of ordinary skill in the art, for the technology, mechanism, manufacturing, material composition, means, method or the step that have existed or be about to later on develop at present, wherein they are carried out the corresponding embodiment cardinal principle identical functions of describing with the utility model or obtain identical substantially result, can use them according to the utility model.Therefore, the utility model claims are intended to these technology, mechanism, manufacturing, material composition, means, method or step are included in its protection domain.