The reagent cartridge that during a kind of material transfer, liquid level tilts
Technical field
The present invention relates to the technical field of nucleic acid extraction, particularly relate to the reagent cartridge that when a kind of material shifts, liquid level tilts.
Background technology
Along with the transformation of medical model and the development of personalized medicine, medical test circle is in the urgent need to detection means fast, accurately, and Molecular Detection has then given play to unique advantage.The basis of Molecular Detection analyzes the histocyte of detected person, hair, anticoagulation or dry bloodstain, and formaldehyde is fixed, gene in paraffin-embedded tissue and expression product thereof, detect by completing nucleic acid (DNA and RNA) from molecular level, in disease once before occurring even not yet to occur symptom, sign and biochemical change, just can accurately detection be made.
At present, molecular detection technology mainly contains making nucleic acid molecular hybridization, polymerase chain reaction (PCR) and biochip technology etc.Molecular Detection product is mainly used in the detection of the clinical departments such as tumour, infection, heredity, Prenatal Screening, and the aspect such as MEC, technical service center, third party feeler mechanism and microbial rapid detection market.Current, the measuring means such as blood routine, cytology, pathology and immunology are all towards automatization, integration, stdn future development, but due to himself technical complexity of Molecular Detection, the full-automatic instrument platform of " from sample to result " is few or there is many insoluble technical problems.Such as, the centrifugal column method used in biological technical field or paramagnetic particle method carry out nucleic acid extraction, generally need to carry out cracking, in conjunction with, rinsing, four steps such as wash-out, add follow-up making nucleic acid molecular hybridization, the detecting steps such as polymerase chain reaction (PCR) and biochip, the full-automatic instrument of whole " from sample to result " is made to be very difficult to realize, single with regard to the transfer of effective constituent in each step, the mode adopting manual transfer in prior art more, namely by artificial mode by raw material or intermediate product step successively and realize step successively reaction vessel in shift, obviously, the manual material tranfer system adopted in prior art, not only complex operation, waste time and energy.Wherein, in existing nucleic acid extraction process, liquid level in each chamber of major part nucleic acid extraction cartridge or nucleic acid extraction structure is in horizontality usually together with whole extraction platform always, and in the transfer process of magnetic bead in adjacent chamber, magnetic bead is dipped in extraction reagent in chamber or reaction solution, the transfer of magnetic bead can take away in the lump extraction reagent in extraction reagent in chamber or reaction solution and chamber or reaction solution dissolve residual impurity, affect purity and the efficiency of extract, and then subsequent experimental result is had a negative impact.
Summary of the invention
For deficiency of the prior art, it is simple that the technical problem that the present invention solves is to provide a kind of structure, the reagent cartridge that when easy to operate material shifts, liquid level tilts, when magnetic bead in nucleic acid extraction process shifts, tilt operation is carried out to extraction platform, namely magnetic bead is separated before magnetic bead shifts with liquid, avoid the liquid incidental impurities produced in the lump with magnetic bead transfer process, improve DNA purity and the efficiency of material to be extracted (protein, nucleic acid).
In order to solve the problems of the technologies described above, the reagent cartridge that during transfer of material that the embodiment of the present invention provides, liquid level tilts comprises the extraction platform of base plate, one end and described base plate pin joint, described extraction platform is provided with the first chamber and the second chamber and by described first chamber and the isolated container cavity of the second chamber, is provided with the magnetic bead transfer organization be transferred to by the magnetic bead in the first chamber in the second chamber in described container cavity; This material transfer time liquid level tilt reagent cartridge be also included in extract platform the other end install by the leaning device of described extraction platform inclination.
As preferred version of the present invention, the reagent cartridge that during a kind of material transfer that embodiments of the invention provide, liquid level tilts comprises the part or all of of following technical characteristic further:
In one embodiment of this invention, described leaning device comprises the flexible thimble between described plate upper surface and extraction platform lower surface, and described flexible thimble moves up and down and drives described extraction platform to be in level or heeling condition under the driving of external force.
In another embodiment of the invention, described leaning device comprises top board, at described top board and the pulley assembly, the stay cord be serially connected with in described pulley assembly that extract between platform, a free end of described stay cord is fixedly connected on the other end of described extraction platform, and another free end of described stay cord is connected with traction motor.
In another embodiment of the invention, described leaning device is spring assist lifting device, comprise the base be positioned on described base plate, elevating lever that one end is connected with described base rotation, the spring that connects described elevating lever and base, the other end of described elevating lever is connected to described extraction platform.
Preferably, described magnetic bead transfer organization comprises cylindricality rotational structure and promotes the screw mandrel of described cylindricality rotational structure rotation, described cylindricality rotational structure is provided with a threaded hole along its axis, is provided with internal thread in described threaded hole, and the outside screw of this internal thread and screw mandrel outside surface matches.
Preferably, the side of described cylindricality rotational structure is provided with the adsorbing plane holding magnetic bead, is also provided with the magnet of absorption magnetic bead in described container cavity; Described adsorbing plane shifts the previous dynasty to described first chamber at magnetic bead, and magnetic bead is adsorbed in described adsorbing plane by described magnet; During magnetic bead transfer, axially screw mandrel is promoted along cylindricality rotational structure, screw mandrel enters in the threaded hole of cylindricality rotational structure, the internal thread that the outside screw of screw mandrel acts on threaded hole promotes cylindricality rotational structure and rotates in container cavity around its axis, and the magnetic bead of described adsorbing plane and adsorbing plane attachment turns to towards in the region of the second chamber.
Preferably, described screw mandrel is provided with a through hole along wherein axis direction, and described magnet interts in described through hole and adsorbs magnetic bead when magnetic bead shift, complete magnetic bead transfer afterwards described magnet exit described through hole.
The reagent cartridge that during the material transfer that the embodiment of the present invention provides, liquid level tilts, has following beneficial effect:
The reagent cartridge that during the material transfer that the embodiment of the present invention provides, liquid level tilts installs leaning device on extraction platform, when magnetic bead in nucleic acid extraction process shifts, tilt operation is carried out to extraction platform, namely magnetic bead is separated before magnetic bead shifts with liquid, avoid the liquid incidental impurities produced in the lump with magnetic bead transfer process, improve DNA purity and the efficiency of material to be extracted (protein, nucleic acid).The present invention arranges container cavity between the first chamber and the second chamber, magnetic bead transfer organization is set in container cavity, the side of the cylindricality rotational structure in this magnetic bead transfer organization is provided with the adsorbing plane holding magnetic bead, adsorbing plane shifts the previous dynasty to described first chamber at magnetic bead, magnetic bead is adsorbed in described adsorbing plane by magnet, therefore, when the magnetic bead of the present invention in nucleic acid extraction process shifts, extraction platform is obliquely installed, the liquid level in each chamber is made not to be be in horizontality always together with whole extraction platform to extract nucleic acid abundant, in the transfer process of magnetic bead in adjacent chamber, namely magnetic bead is separated before magnetic bead shifts with liquid, improve the DNA purity of nucleic acid.
Accompanying drawing explanation
Fig. 1 be the embodiment of the present invention one provide material transfer time the liquid level structural representation of reagent cartridge that tilts.
Fig. 2 be the embodiment of the present invention two provide material transfer time the liquid level structural representation of reagent cartridge that tilts.
Fig. 3 be the embodiment of the present invention three provide material transfer time the liquid level structural representation of reagent cartridge that tilts.
Embodiment
Below in conjunction with the accompanying drawing in the embodiment of the present invention, be clearly and completely described the technical scheme in the embodiment of the present invention, obviously, described embodiment is only the present invention's part embodiment, instead of whole embodiments.Based on the embodiment in the present invention, those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.
The reagent cartridge that during material transfer of the present invention, liquid level tilts is applied in nucleic acid preparation and test set, be intended to for the material transfer in nucleic acid preparation and testing process between adjacent step provide one efficiently, solution efficiently, but not as limit, in actual applications, also can be applicable to the extraction of other biological extract.
Embodiment one
As Fig. 1, the reagent cartridge that during transfer of material that the embodiment of the present invention one provides, liquid level tilts comprises the extraction platform 30 of base plate 10, one end and described base plate 10 pin joint, described extraction platform 30 is provided with the first chamber and the second chamber and by described first chamber and the isolated container cavity of the second chamber, is provided with the magnetic bead transfer organization be transferred to by the magnetic bead in the first chamber in the second chamber in described container cavity, this material transfer time liquid level tilt reagent cartridge be also included in extract platform the other end install by the leaning device 40 of described extraction platform inclination, described leaning device 40 comprises the flexible thimble 41 between described plate upper surface and extraction platform lower surface, described flexible thimble 41 moves up and down and drives described extraction platform 30 to be in level or heeling condition under the driving of external force, by flexible thimble 41, tilt operation is carried out to extraction platform 30 when magnetic bead in nucleic acid extraction process shifts, namely magnetic bead is separated before magnetic bead shifts with liquid, avoid the liquid incidental impurities produced in the lump with magnetic bead transfer process, improve material (protein to be extracted, nucleic acid) DNA purity and efficiency.
During specific implementation, magnetic bead transfer organization comprises cylindricality rotational structure and promotes the screw mandrel of cylindricality rotational structure rotation, in specific implementation process, cylindricality rotational structure to be arranged in container cavity and to be formed with container cavity and seals container cavity and the first chamber and the second chamber are separated, cylindricality rotational structure is provided with a threaded hole along its axis, be provided with internal thread in threaded hole, the outside screw of this internal thread and screw mandrel outside surface matches.When screw mandrel longitudinally advances along cylindricality rotational structure, by screw-driven, screw mandrel axial translation is converted into the rotation of cylindricality rotational structure, and cylindricality rotational structure is rotated in container cavity.
In order to fully, efficiently shift magnetic bead, the side of cylindricality rotational structure is provided with the adsorbing plane holding magnetic bead, is also provided with the magnet (not shown) of absorption magnetic bead in container cavity.In principle, the present invention is mainly by adopting the magnetic-particle comprising magnetic bead as extraction nucleic acid or other macromole bio-extracts, magnetic bead realizes the adsorption to nucleic acids in samples or other macromole bio-extracts at the first chamber, the magnetic bead in the first chamber in mixture is adsorbed with nucleic acid to be extracted or other macromole bio-extracts.Now, namely before magnetic bead transfer, adsorbing plane is towards the first chamber, and magnetic bead is adsorbed in adsorbing plane by magnet; When magnetic bead shifts, axially screw mandrel is promoted along cylindricality rotational structure, screw mandrel enters in the threaded hole of cylindricality rotational structure, the internal thread that the outside screw of screw mandrel acts on threaded hole promotes cylindricality rotational structure and rotates in container cavity around its axis, and the magnetic bead held in adsorbing plane and adsorbing plane turns to towards in the region of the second chamber.By local, the side of cylindricality rotational structure is set to adsorbing plane, and make adsorbing plane adsorb the previous dynasty to the first chamber, treat that magnetic bead is adsorbed onto on this adsorbing plane under the effect of magnetic force, promote cylindricality rotational structure by screw mandrel again to rotate through container cavity, in rotation process adsorbing plane and container cavity curved surface chamber wall between can form arcuate gap, and be adsorbed on magnetic bead on adsorbing plane can not be received chamber chamber wall because of the existence of arcuate gap for this reason and scrape from coming off, thus realize material transfer effectively, cylindricality rotational structure is mated except other positions of adsorbing plane can seal with container cavity simultaneously, ensure that the mutual independence of unclassified stores between the first chamber and the second chamber except magnetic bead.
In addition, from the vibrational power flow of the joining place of the first chamber and the second chamber and container cavity, in order to fully, efficiently magnetic bead can be shifted, the joining place of the first chamber and container cavity is set to the contraction structure narrowed gradually, at the cohesive position of the first chamber and cylindricality rotational structure, the first chamber contraction is to the width corresponding with described adsorbing plane.Correspondingly, the joining place of the second chamber and container cavity is also set to the contraction structure narrowed gradually, and at the cohesive position of the second chamber and cylindricality rotational structure, the second chamber contraction is to the width corresponding with described adsorbing plane.For this reason, the joining place of the first chamber and the second chamber and container cavity can be set to the structure that chamfering receives limit.
In a preferred embodiment of the invention, the first chamber and the second chamber arranged in parallel, therefore, during magnetic bead transfer, screw mandrel needs to promote cylindricality rotational structure and rotate half cycle in container cavity, and correspondingly, the axial translation of screw mandrel advances this to be of a size of half pitch.Certainly in other embodiments of the present invention, first chamber and the second chamber can not parallelly be arranged, and there is certain angle in the two, and now, screw mandrel advances size and cylindricality rotational structure angle also to be determined by the angle between the first chamber and the second chamber, thus the magnetic bead in the first chamber is transferred in the second chamber accurately and efficiently.
In embodiments of the invention one, screw mandrel is provided with a through hole along wherein axis direction, and magnet interts in through hole and adsorbs magnetic bead when magnetic bead shift, complete magnetic bead transfer afterwards magnet exit through hole.In this scheme, the mode of operation of magnetic bead transfer organization is: before magnetic bead transfer, and adsorbing plane is towards the first chamber, and magnet interts in through hole and adsorbs magnetic bead, is adsorbed to by magnetic bead in adsorbing plane; When magnetic bead shifts, axially screw mandrel is promoted along cylindricality rotational structure, screw mandrel enters in the threaded hole of cylindricality rotational structure, the internal thread that the outside screw of screw mandrel acts on threaded hole promotes cylindricality rotational structure and rotates in container cavity around its axis, and the magnetic bead held in adsorbing plane and adsorbing plane turns to towards in the region of the second chamber; When the magnetic bead held in adsorbing plane and adsorbing plane turns to after the second chamber, magnet exits in through hole, and magnetic bead, owing to losing the adsorption of magnet magnetic force, is dispersed in the second chamber.
In an embodiment of the present invention, the both sides of magnetic bead transfer organization are provided with the magnet that two are parallel to cylindricality rotational structure axis, and magnet produces contrary toroidal magnetic field, direction, thus makes magnetic bead move to adsorbing plane.In this scheme, the mode of operation of magnetic bead transfer organization is: before magnetic bead transfer, and adsorbing plane, towards the first chamber, under the magneticaction that magnetic bead is formed in toroidal magnetic field, concentrate in adsorbing plane, and this field direction is identical with the shift direction of magnetic bead; When magnetic bead shifts, axially screw mandrel is promoted along cylindricality rotational structure, screw mandrel enters in the threaded hole of cylindricality rotational structure, the internal thread that the outside screw of screw mandrel acts on threaded hole promotes cylindricality rotational structure and rotates in container cavity around its axis, and the magnetic bead held in adsorbing plane and adsorbing plane turns to towards in the region of the second chamber.
Embodiment two
As Fig. 2, the reagent cartridge that during transfer of material that the embodiment of the present invention two provides, liquid level tilts comprises the extraction platform 30 of base plate 10, one end and described base plate 10 pin joint, described extraction platform 30 is provided with the first chamber and the second chamber and by described first chamber and the isolated container cavity of the second chamber, is provided with the magnetic bead transfer organization be transferred to by the magnetic bead in the first chamber in the second chamber in described container cavity, this material transfer time liquid level tilt reagent cartridge be also included in extract platform the other end install by the leaning device 40 of described extraction platform inclination, described leaning device 40 comprises top board 20, pulley assembly 43 between described top board 20 and extraction platform 30, be serially connected with the stay cord 44 in described pulley assembly 43, a free end of described stay cord 44 is fixedly connected on the other end of described extraction platform 30, another free end of described stay cord 44 is connected with traction motor 45, traction motor 45 pairs of stay cords 44 produce downward pulling force, thus extraction platform 30 is tilted, and then make the first chamber 31, second chamber 32 and transfer chamber 33 tilt, by pulley assembly 43, tilt operation is carried out to extraction platform 30 when magnetic bead in nucleic acid extraction process shifts, namely magnetic bead is separated before magnetic bead shifts with liquid, avoid the liquid incidental impurities produced in the lump with magnetic bead transfer process, improve material (protein to be extracted, nucleic acid) DNA purity and efficiency.
During specific implementation, magnetic bead transfer organization comprises cylindricality rotational structure and promotes the screw mandrel of cylindricality rotational structure rotation, in specific implementation process, cylindricality rotational structure to be arranged in container cavity and to be formed with container cavity and seals container cavity and the first chamber and the second chamber are separated, cylindricality rotational structure is provided with a threaded hole along its axis, be provided with internal thread in threaded hole, the outside screw of this internal thread and screw mandrel outside surface matches.When screw mandrel longitudinally advances along cylindricality rotational structure, by screw-driven, screw mandrel axial translation is converted into the rotation of cylindricality rotational structure, and cylindricality rotational structure is rotated in container cavity.
In order to fully, efficiently shift magnetic bead, the side of cylindricality rotational structure is provided with the adsorbing plane holding magnetic bead, is also provided with the magnet (not shown) of absorption magnetic bead in container cavity.In principle, the present invention is mainly by adopting the magnetic-particle comprising magnetic bead as extraction nucleic acid or other macromole bio-extracts, magnetic bead realizes the adsorption to nucleic acids in samples or other macromole bio-extracts at the first chamber, the magnetic bead in the first chamber in mixture is adsorbed with nucleic acid to be extracted or other macromole bio-extracts.Now, namely before magnetic bead transfer, adsorbing plane is towards the first chamber, and magnetic bead is adsorbed in adsorbing plane by magnet; When magnetic bead shifts, axially screw mandrel is promoted along cylindricality rotational structure, screw mandrel enters in the threaded hole of cylindricality rotational structure, the internal thread that the outside screw of screw mandrel acts on threaded hole promotes cylindricality rotational structure and rotates in container cavity around its axis, and the magnetic bead held in adsorbing plane and adsorbing plane turns to towards in the region of the second chamber.By local, the side of cylindricality rotational structure is set to adsorbing plane, and make adsorbing plane adsorb the previous dynasty to the first chamber, treat that magnetic bead is adsorbed onto on this adsorbing plane under the effect of magnetic force, promote cylindricality rotational structure by screw mandrel again to rotate through container cavity, in rotation process adsorbing plane and container cavity curved surface chamber wall between can form arcuate gap, and be adsorbed on magnetic bead on adsorbing plane can not be received chamber chamber wall because of the existence of arcuate gap for this reason and scrape from coming off, thus realize material transfer effectively, cylindricality rotational structure is mated except other positions of adsorbing plane can seal with container cavity simultaneously, ensure that the mutual independence of unclassified stores between the first chamber and the second chamber except magnetic bead.
In addition, from the vibrational power flow of the joining place of the first chamber and the second chamber and container cavity, in order to fully, efficiently magnetic bead can be shifted, the joining place of the first chamber and container cavity is set to the contraction structure narrowed gradually, at the cohesive position of the first chamber and cylindricality rotational structure, the first chamber contraction is to the width corresponding with described adsorbing plane.Correspondingly, the joining place of the second chamber and container cavity is also set to the contraction structure narrowed gradually, at the cohesive position of the second chamber and cylindricality rotational structure, second chamber contraction is to the width corresponding with described adsorbing plane, for this reason, the joining place of the first chamber and the second chamber and container cavity can be set to the structure that chamfering receives limit.
In a preferred embodiment of the invention, the first chamber and the second chamber arranged in parallel, therefore, during magnetic bead transfer, screw mandrel needs to promote cylindricality rotational structure and rotate half cycle in container cavity, and correspondingly, the axial translation of screw mandrel advances this to be of a size of half pitch.Certainly in other embodiments of the present invention, first chamber and the second chamber can not parallelly be arranged, and there is certain angle in the two, and now, screw mandrel advances size and cylindricality rotational structure angle also to be determined by the angle between the first chamber and the second chamber, thus the magnetic bead in the first chamber is transferred in the second chamber accurately and efficiently.
In embodiments of the invention two, screw mandrel is provided with a through hole along wherein axis direction, and magnet interts in through hole and adsorbs magnetic bead when magnetic bead shift, complete magnetic bead transfer afterwards magnet exit through hole.In this scheme, the mode of operation of magnetic bead transfer organization is: before magnetic bead transfer, and adsorbing plane is towards the first chamber, and magnet interts in through hole and adsorbs magnetic bead, is adsorbed to by magnetic bead in adsorbing plane; When magnetic bead shifts, axially screw mandrel is promoted along cylindricality rotational structure, screw mandrel enters in the threaded hole of cylindricality rotational structure, the internal thread that the outside screw of screw mandrel acts on threaded hole promotes cylindricality rotational structure and rotates in container cavity around its axis, and the magnetic bead held in adsorbing plane and adsorbing plane turns to towards in the region of the second chamber; When the magnetic bead held in adsorbing plane and adsorbing plane turns to after the second chamber, magnet exits in through hole, and magnetic bead, owing to losing the adsorption of magnet magnetic force, is dispersed in the second chamber.
In an embodiment of the present invention, the both sides of magnetic bead transfer organization are provided with the magnet that two are parallel to cylindricality rotational structure axis, and magnet produces contrary toroidal magnetic field, direction, thus makes magnetic bead move to adsorbing plane.In this scheme, the mode of operation of magnetic bead transfer organization is: before magnetic bead transfer, and adsorbing plane, towards the first chamber, under the magneticaction that magnetic bead is formed in toroidal magnetic field, concentrate in adsorbing plane, and this field direction is identical with the shift direction of magnetic bead; When magnetic bead shifts, axially screw mandrel is promoted along cylindricality rotational structure, screw mandrel enters in the threaded hole of cylindricality rotational structure, the internal thread that the outside screw of screw mandrel acts on threaded hole promotes cylindricality rotational structure and rotates in container cavity around its axis, and the magnetic bead held in adsorbing plane and adsorbing plane turns to towards in the region of the second chamber.
Embodiment three
As shown in Figure 3, the reagent cartridge that during the material transfer that the embodiment of the present invention three provides, liquid level tilts only is following aspect with the difference implementing the reagent cartridge that liquid level a tilts when material provided shifts: described leaning device 40 is spring assist lifting device, comprise the base 42 be positioned on described base plate, the elevating lever 46 that one end and described base 42 are rotationally connected, connect the spring 47 of described elevating lever 46 and base 42, the other end of described elevating lever 46 is connected to described extraction platform 30, by spring assist lifting device, tilt operation is carried out to extraction platform 30 when magnetic bead in nucleic acid extraction process shifts, namely magnetic bead is separated before magnetic bead shifts with liquid, avoid the liquid incidental impurities produced in the lump with magnetic bead transfer process, improve material (protein to be extracted, nucleic acid) DNA purity and efficiency.
For selection and the material of magnet, during specific implementation, magnet is permanent magnet or electromagnet.Select permanent magnet in an embodiment of the present invention or extraordinary preferred version can be by the electromagnet of energising control.And in the embodiment of the present invention one to embodiment three, adopt electromagnet can not only produce required toroidal magnetic field easily and efficiently, and the action time in magnetic field (i.e. magnetic bead transfer time) can be accurately controlled, after magnetic bead is transferred to the second chamber, magnetic bead rapid dispersion from adsorbing plane further reacts in the second chamber.
The reagent cartridge that during the material transfer that above-described embodiment discloses, liquid level tilts installs leaning device 40 on extraction platform 30, when magnetic bead in nucleic acid extraction process shifts, tilt operation is carried out to extraction platform 30, namely magnetic bead is separated before magnetic bead shifts with liquid, avoid the liquid incidental impurities produced in the lump with magnetic bead transfer process, improve DNA purity and the efficiency of material to be extracted (protein, nucleic acid).The present invention arranges container cavity between the first chamber and the second chamber, magnetic bead transfer organization is set in container cavity, the side of the cylindricality rotational structure in this magnetic bead transfer organization is provided with the adsorbing plane holding magnetic bead, adsorbing plane shifts the previous dynasty to described first chamber at magnetic bead, magnetic bead is adsorbed in described adsorbing plane by magnet, therefore, when the magnetic bead of the present invention in nucleic acid extraction process shifts, extraction platform 30 is obliquely installed, the liquid level in each chamber is made not to be be in horizontality always together with whole extraction platform 30 to extract nucleic acid abundant, in the transfer process of magnetic bead in adjacent chamber, namely magnetic bead is separated before magnetic bead shifts with liquid, improve the DNA purity of nucleic acid.
The above is the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications are also considered as protection scope of the present invention.