CN100434181C - Metering doses of sample liquids - Google Patents
Metering doses of sample liquids Download PDFInfo
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- CN100434181C CN100434181C CNB2005800051996A CN200580005199A CN100434181C CN 100434181 C CN100434181 C CN 100434181C CN B2005800051996 A CNB2005800051996 A CN B2005800051996A CN 200580005199 A CN200580005199 A CN 200580005199A CN 100434181 C CN100434181 C CN 100434181C
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Abstract
A method of metering and mixing a dose of a sample liquid (17) with a diluent liquid (20) includes introducing a sample liquid (17) into a channel (33, 102) defined in a housing. The housing defines a pocket (13, 26, 28, 29, 34, 35, 38) open to the channel (33, 102) and sized to both collect a metered dose of the sample liquid (17), and to retain the collected dose by capillary force when the channel (33, 102) is emptied. The sample liquid (17) is then removed from the channel (33, 102) under conditions that enable retention of the collected, metered dose of the sample liquid (17) in the pocket (13, 26, 28, 29, 34, 35, 38). Following a cleaning step, a volume of diluent liquid (20) is introduced into the channel (33, 102) to induce diffusion and mixing of the diluent liquid (20) with the dose of sample liquid (17) to form a mixture (21).
Description
Technical field
The present invention relates to liquid transporting device such as pipette in the sample liquids of metering doses, and mix this sample liquids with diluent liquid.
Background technology
Along with the development in fields such as gene, synthetic chemistry and high throughput screening, variation has also taken place in the science of drug invention and economy.When the quantity of micromolecular compound (sample) obtained phenomenal growth owing to synthetic chemistry, the quantity of target was also owing to gene obtains increasing.The quantity of the test of carrying out has exponential other influence in order to increase the possibility of using high throughput screening discovery new drug to those in the growth of this target and compound.The target of microlitre quantity and sample must satisfy many screening calibratings, and this has applied pressure to automatic factory, make it provide new instrument to increase high yield, increase efficient, and reduce R﹠amp; The D cost.Traditional R﹠amp; The D screening operation uses the multiple variation move liquid that the aliquot of concentrated liquid sample is moved to Work container from storage container, to cut-back tank, moves to the calibrating container at last.This " reformation " process, or " sample preparation " increased the complexity of whole process, wasted valuable sample or target, and increased time and calibrating cost.
Disposable pipette tip and non-once, sterilizable liquid-transfering device are generally used for ratio liquid.The inlet that pipette tip and liquid-transfering device include an end and the other end are used to be connected the positioning port of liquid-transfering device.Liquid-transfering device is surrounded by the directed travel mechanism of piston-cylinder usually.The pipette tip is connected on the liquid-transfering device by a plurality of mechanical connecting devices.Air column is connected to the pipette loss of head with piston-cylinder mechanism by fluid boundary.When the inlet of pipette tip immerses in the liquid, and piston-cylinder mechanism is when inwardly inhaling, and liquid is inhaled into the pipette tip.The liquid of air column and suction is measured in proportion and is entered the pipette tip.Counter motion by piston-cylinder mechanism discharges liquid from tip.The amount of the liquid that can suck and discharge is subjected to a plurality of effects limit, and these factors include but not limited to: the restriction of pipette tip material, pipette tip Surface Machining, inlet capillary force, surface energy of liquid and piston-cylinder mechanism.
Pipe, capillary channel and plate surface composition the classification of device, this device is used for multiple market to be used, and comprises the handover of liquid.In drug discovery market, new development comprises that capillary channel comes moving liquid by countless systematic procedures in the field of the system on " small pieces " little basis.In diagnosis market, pipe and liquid-transfering device are used to carry out many liquid testings, and its trouble is the contrast of amount with the quantity of the test that relies on those source liquid to carry out of limited source liquid.
Summary of the invention
Generally speaking, one aspect of the present invention provides a kind of sample liquids of metering doses and the method for mixing this sample liquids with diluent liquid, comprise sample liquids is incorporated in the passage that is limited in the housing, this housing defines the recess that opens wide to passage, the size of this recess manufactures at the sample liquids of passage for collection dosing in empty, and keeps the dosage of collecting by capillary force; Under the condition of the sample liquids of the dosing that can keep collecting in the recess, sample liquids is removed from passage; Diluent liquid with certain volume is incorporated in the passage then, with the diluent liquid diffusion, and with this diluent liquid and sample liquids mixing formation mixture.
Some embodiment be included in sample liquids from passage, remove after and before being incorporated into diluent liquid in the passage, clean described passage.Cleaning step comprises cleaning fluid is incorporated into position below the described recess in the passage; Then cleaning fluid is removed from passage, wash residual sample liquid any on the channel surface below the described recess.
In some cases, described housing comprises the pipe that defines passage, and in these cases, described pipe can have open lower end, is introduced into by liquid suction line subsample liquid is passed this open lower end.Described passage can be narrower, and/or described recess can be arranged in the part than the passage of the channel width of the open end of pipe.Described recess can comprise the upwardly extending otch that is limited in the described tube wall.The surface of described pipe can limit the following extension degree of described recess, and this surface is basically perpendicular to the longitudinal axis of described pipe.In certain embodiments, described recess can be elongated and be parallel to the longitudinal axis of described pipe.
In some cases, described housing comprises plywood, and this plywood defines fluid passage, recess and the inlet that contacts with described passage fluid.In these cases, sample liquids can be pneumatically to be drawn into the passage neutralization to discharge from passage.
In certain embodiments, this method comprises that also the mixture with metered volume is assigned in the target shrinkage pool.Can pneumatically from described housing, promote mixture and distribute described mixture.Equally, also can from described housing, promote described mixture by gas-pressurized.
In some cases, the described volume that is incorporated into the diluent liquid in the passage is between about 1 millilambda and about 1 milliliter.
In certain embodiments, described housing defines apart from one another by a plurality of described recess that is provided with.
Enforcement can comprise one or more following features.Such as, can select the method for forming, machining, welding and coating, perhaps other is suitable is used to produce capillary and keeps the methods of feature to form described recess.Described recess can be by being that safe material constitutes to the material that forms described shell inner surface.Described recess can be limited in the projection, and described projection extends in the described passage.
On the other hand, the invention provides a kind of sample liquids of metering doses and the method for mixing this sample liquids with diluent liquid, comprise sample liquids is drawn in the pipette, this pipette defines inner chamber, and having the inwall that limits recess, the size of this recess manufactures the sample liquids of collecting dosing; Then under the condition of the sample liquids of the dosing that can keep by capillary force collecting in the recess, sample liquids is removed from pipette; Diluent liquid with certain volume is drawn into distance enough in the pipette then, so that the sample liquids of contact retained dose spreads diluent liquid, and the sample liquids of this diluent liquid and this dosage is mixed.
Some embodiment be included in sample liquids from pipette, discharge after and before being drawn into diluent liquid in the pipette, clean described pipette.Cleaning step comprises cleaning fluid is drawn into the position below described recess in the pipette; Then cleaning fluid is discharged from pipette, so that wash out any residual sample liquid from the inner wall surface below described recess.
In certain embodiments, this method comprises that also the mixture with metered volume is assigned in the target shrinkage pool.Can pneumatically from described pipette, promote mixture and discharge described mixture.In some cases, described pipette also limits pore between the outer surface of described pipette and inner chamber.In these cases, enter described inner chamber and come from described pipette to promote described mixture by forcing gas-pressurized to pass described pore.
In some cases, described inner chamber is narrow on the top of pipette at the lower open end ratio of pipette.In these cases, described recess can be arranged on the part of the inner chamber wideer than the inner chamber of the open end of pipette.
In certain embodiments, the described pipette surface that limits extension degree under the described recess is basically perpendicular to the longitudinal axis of described pipette.
In some cases, described recess is elongated and is parallel to the longitudinal axis of described pipette.
In certain embodiments, the described volume of the diluent liquid in the inner chamber that is incorporated into is between about 1 millilambda and about 500 microlitres.
In some cases, described pipette can limit the axle that is parallel to described pipette or radially apart from one another by a plurality of described recess that is provided with.
Enforcement can comprise one or more following features.Such as, described pipette can be formed by synthetic resin, can select the method for forming, machining, welding and coating, and perhaps other is suitable is used to produce capillary and keeps the method for feature to form described recess.Equally, described recess can be limited in the projection, and described projection extends in the described passage.
On the other hand, the invention provides a kind of sample liquids of metering doses and the method for mixing this sample liquids with diluent liquid, comprise the pipette array is provided, each pipette defines inner chamber, and having the inwall that limits recess, the size of this recess manufactures the sample liquids of collecting dosing; Sample liquids is drawn in the pipette; Then under the condition of the sample liquids of the dosing that can keep by capillary force collecting in the recess, sample liquids is discharged from pipette; Diluent liquid with certain volume is drawn into distance enough in the pipette then, so that the sample liquids of the doses that contact keeps, with the diluent liquid diffusion, and with this diluent liquid and sample liquids mixing.
Some embodiment be included in sample liquids from pipette, discharge after and before being drawn into diluent liquid in the pipette, clean described pipette.Cleaning step comprises cleaning fluid is drawn into the position below described recess in the pipette; Then cleaning fluid is discharged from pipette, come from any residual sample liquid of the flushing of the inner wall surface below described recess.
In certain embodiments, this method comprises that the mixture with metered volume is assigned to the target shrinkage pool from each pipette.The volume of distribution and computation can comprise pneumatically promote mixture from described pipette.Equally, each pipette also defines pore between the outer surface of described pipette and inner chamber, and enters described inner chamber to promote described mixture from described pipette by forcing gas-pressurized to pass described pore.
In certain embodiments, described inner chamber is narrow on the top of pipette at the lower open end ratio of pipette.In these embodiments, described recess can be arranged in the part of the inner chamber wideer than the inner chamber of the open end of pipette.
In some cases, described recess comprises the upwardly extending otch that is limited in the pipette inwall.
In certain embodiments, the described pipette surface that limits extension degree under the described recess is basically perpendicular to the longitudinal axis of described pipette.
In some cases, described recess is elongated and is parallel to the longitudinal axis of described pipette.
In certain embodiments, the described volume of the diluent liquid in the inner chamber that is incorporated into is between about 1 millilambda and about 500 microlitres.
In some cases, described pipette can limit the axle that is parallel to described pipette or radially apart from one another by a plurality of described recess that is provided with.
In certain embodiments, this method comprises that the mixture with metered volume is assigned in the array of liquid receiving element.In these embodiments, the array of pipette directly is arranged in the top of the array of described liquid receiving element.The array of described liquid receiving element can comprise porous container.Described porous container is to select from the cohort of being made up of 96 hole microtiter plates, 384 hole microtiter plates and 1536 hole microtiter plates.
Enforcement can comprise one or more following features.Such as, this method can comprise that the mixture with metered volume is assigned on the slide.Equally, this method can comprise that the mixture with metered volume is assigned on the electronics calibrating reading device (electronic assay reading device).
In one aspect, the invention provides a kind of pipette, comprise elongated body, this body has outer surface, and defines the inner chamber that opens wide in described body lower end; Described body defines the opening on this body top, can pass this opening sucking-off air from described inner chamber, and the lower end of liquid by described body is drawn in the inner chamber; Wherein, described body has the inwall that defines the recess that opens wide to inner chamber, and the size of this recess manufactures the liquid of being collected and keep the dosing that is inhaled into described inner chamber at inner chamber when finding time in addition.
In some embodiment of device, a plurality of molded inner recess or outer recess appear, the volume of the liquid of different final distribution is provided.In some embodiment of device, inner recess or outer recess can adopt other method manufacturing beyond the method for forming, such as the recess of machining, the recess of welding, recess of coating or the like.In some embodiment of device, described recess can be the sub section (such as Overmolded or embedding moulding section) that is connected on the liquid transporting device.
In some cases, described body also defines the pore that extends to inner chamber from outer surface.
In some cases, described recess is arranged in the part of the inner chamber wideer than the inner chamber of the open end of body.
In certain embodiments, described recess comprises the upwardly extending otch that is limited in the inner body wall.
In some cases, the described pipette surface that limits extension degree under the described recess is basically perpendicular to the longitudinal axis of described body.
Enforcement can comprise one or more following features.Such as, described body can be formed by synthetic resin, and described body can limit the axle that is parallel to described pipette or radially apart from one another by a plurality of described recess that is provided with.Equally, described recess can be limited in the projection, and described projection extends in the described inner chamber.
Above-mentioned any one enforcement can comprise one or more following features.The size of described recess preferably manufactures the sample liquids of the dosing of collected volume between about 1 millilambda and about 10 microlitres, more preferably, the size of described recess manufactures the sample liquids of the dosing of collected volume between about 5 millilambdas and about 10 microlitres.The size of described recess preferably width between about 0.001 to 0.04 inch (0.025 to 1.02 millimeter), and the degree of depth is between about 0.001 to 0.1 inch (0.025 to 2.54 millimeter), more preferably, width is between about 0.008 to 0.020 inch (0.204 to 0.51 millimeter), and the degree of depth is between about 0.008 to 0.04 inch (0.204 to 1.02 millimeter).The length of described recess is preferably between about 0.01 to 1 inch (0.25 to 25 millimeter).The qualification subclass of feature comprises very little recess wall radius, and it is preferably between about 0.0005 to 0.005 inch (0.013 to 0.127 millimeter), and its grain surface processing is in 2 microns to 256 microns scope.It is round mobile that described diluent liquid can repeatedly be passed described recess, and it is mixed with the sample liquids of this dosage.
Device disclosed herein is to be designed to capture the repeatably volume of source liquid by surface tension, geometry or chemical attachment.These devices can comprise that pipe, plate, shrinkage pool or storage container, capillary channel, disposable and non-once pipette tip, major function are moving liquids by capillary channel, pipe and pipette tip for the instrument of drawing and discharge liquid and major function or pass the instrument of plate.All devices all are intended to comprise following notion among the present invention: the source liquid of metering fixed dosage or variable dose, in above-mentioned recess, capture them, and then utilize second kind of liquid with its dilution and mixing.This mixture can be all or part of be assigned with, be stored in pipe, pipette tip or the passage, perhaps move to other position by capillary channel or plate.
This device can adopt in life science or the medical diagnosis industry common material to make.The prevailing material that is used for disposable pipette tip is a polypropylene, and it can add pigment, carbon or other has articles for use or the additional product of increased functionality.Disposable pipette tip also can adopt other moulding plastics such as polypropylene, polystyrene, Merlon or other material manufacturing.Non-once pipette tip often adopts stainless steel, glass or other metal or the plastics of various grades to make, and often plates the coating that discharges water such as Teflon
TMOr Parylene
TM
Below with reference to accompanying drawing and explanation one or more embodiments of the detail of the present invention are described.Other feature, purpose and advantage of the present invention will be from specification and accompanying drawing, and obtains in the claim embodying.
Description of drawings
Fig. 1 is the side view of pipette pointed device;
Figure 1A is the cutaway view along the line 1A-1A among Fig. 1;
Fig. 2 is arranged in the perspective view of admitting on the plate for the alignment of pipette tip;
Fig. 2 A is the cutaway view that is connected to the pipette tip array of pipette connector array and pipettor;
The cutaway view of the single pipette tip when Fig. 3 admits in the source that is stored in for the tip inlet immerses in the source liquid in the plate;
Fig. 4 is inhaled in the inlet for source liquid and the cutaway view of the single pipette tip when contacting with the molded recess of inside;
The cutaway view of the single pipette tip when Fig. 5 admits in the plate for source liquid is restored to the source;
Fig. 6 also is retained in the cutaway view of the single pipette tip in the pipette tip recess of inner molded for demonstration source liquid;
Fig. 6 A is the cutaway view that demonstration source liquid also is retained in the single pipette tip in the recess of an inner molded;
Fig. 7 is arranged in the cutaway view of the single pipette tip on the system liquid receiver for the pipette tip;
The cutaway view of the single pipette tip when Fig. 8 is inhaled into inlet for system liquid;
The cutaway view of the single pipette tip of Fig. 9 when the system liquid that sucks is between upper and lower inner molded recess;
The cutaway view of the single pipette tip of the end-state that Figure 10 mixes from two inner molded recesses for display system liquid and source liquid;
Figure 11 is the cutaway view of the single pipette tip of the pore of demonstration transparent walls;
Figure 11 A is the cutaway view along the line 11A-11A among Figure 11;
Figure 12 is the side view of single pipette tip;
Figure 12 A is the cutaway view along the line 12A-12A among Figure 12, has shown that another extends into the inner molded element of pipette tip from inner surface;
Figure 13 is the isometric view of single pipette tip;
Figure 13 A is the cutaway view of the pipette tip shown in Figure 13, has shown that another comprises the inner molded element that how much of measurements and plane process and extend into the pipette tip from inner surface;
Figure 13 B is the amplification detail view of the pipette tip cutaway view shown in Figure 13 A;
Figure 14 is the three-dimensional cutaway view that includes the pipe of one or more inner members, and this inner member measures source liquid by geometry and Surface Machining;
Figure 14 A is the side sectional view of the pipe shown in Figure 14;
Figure 15 should " small pieces " include one or more inner members for being present in the isometric cross-sectional view of the capillary channel on " small pieces (chip) ", played by its geometry and Surface Machining and measured source liquid; In case place on the small pieces, handle sample by the passage of small pieces so that mix, cultivate, react, separate and detect required step; As be known in the art, the motion of passing passage is controlled in uniting of working pressure and/or voltage;
Figure 15 A is the side sectional view of the capillary small pieces shown in Figure 15;
Figure 16 is the three-dimensional cutaway view that includes the plate of one or more inner members, and this inner member measures source liquid by its geometry and Surface Machining;
Figure 17 includes continuous radial projection part, forms the cutaway view that capillary keeps the pipette tip of feature; And Figure 17 A is the enlarged diagram of regional 17A among Figure 17;
Figure 18 forms the cutaway view that capillary keeps the pipette tip of feature for comprising a series of discontinuous radial projection parts; And Figure 18 A is the enlarged diagram of regional 18A among Figure 18.
In each accompanying drawing, similarly Reference numeral is represented similar elements.All pipette tips be comprise disposable, non-once and with pipe for based on the liquid transporting device of pipe.
The specific embodiment
Fig. 1 to Figure 1A has shown first kind of pipette pointed device 10.With reference to Figure 1A, pipette tip 10 has inlet 11 and positioning port 12.The function of inner molded recess 13 is the source liquid that absorbs and hold fixed amount.Pipette tip 10 comprises pipe 27, and this pipe 27 defines the path 10 2 that extends along the pipe longitudinal axis 110.Recess 13 opens wide to path 10 2, and is limited by the molded inner surface 104 of pipe 27.Pipe 27 has open lower end 106, enters pipe by imbitition, and sample liquids 17 passes this open lower end 106 and is introduced into.Path 10 2 is narrow on the top 108 of pipe 27 at the lower end of pipe 27 106 ratios.
Fig. 2 is the perspective view that is connected to pipette tip 10 arrays of pipette connector array 16.Pipette tip 10 arrayed are above microtiter plate 14, and this microtiter plate 14 can comprise different arranging densities, such as 96,384 and 1536.The shrinkage pool 15 that each pipette tip 10 is aimed at separately.
Fig. 2 A is the cutaway view that is connected to the pipette tip array of pipette connector array 16, and this pipette connector array 16 is connected with pipettor 39.Pipettor 39 is made up of the array of pipettor cylinder 40 that is used for the positive displacement effect and pipettor piston 41 usually.
Below explain the operation of pipette pointed device 10 by Fig. 3 to Figure 10.
In Fig. 3, microtiter plate 14 includes the source liquid 17 in each independent shrinkage pool 15.The inlet 11 of pipette tip 10 immerses in the source liquid 17.
In Fig. 4, by pipette connector array 16, pipettor is drawn into source liquid 17 in the pipette tip 10 by inlet 11.Source liquid 17 is drawn to the level identical with inner molded recess or a plurality of recess 13, or is drawn to higher level.
In Fig. 5, by pipette connector array 16, pipettor is discharged pipette tip 10 with source liquid 17 by inlet 11 and is distributed.The further motion of pipette actuating device will begin air 18 is released inlet 11.
In Fig. 6, the microtiter plate 14 with source liquid 17 is removed.Each inner molded recess captures and remains with the source liquid 17 of fixed amount.
In Fig. 6 A, shown the enlarged drawing of the inner molded recess 13 of filling active liquid 17.
In Fig. 7, second microtiter plate 14 with the dilution system liquid 20 in each independent shrinkage pool 15 is moved to pipette tip 10 and contacts, and makes inlet 11 be submerged.
In Fig. 8, by pipette connector array 16, pipettor is drawn in the pipette tip 10 by the dilution system liquid 20 of inlet 11 with fixed amount.
In Fig. 9, dilution system micro-amounts of liquids titer plate 14 is removed.By pipette connector array 16, pipettor 39 with the dilution system liquid 20 of fixed amount in pipette tip 10, inhale higher.When system liquid 20 is recessed 13 the time through inner molded, remains in source liquid 17 diluted system liquid 20 in the recess 13 and capture and become mixture 21.By pipette connector array 16, pipettor 39 mixes one or many up and down with system liquid 20 and forms mixture 21.
In Figure 10, by pipette connector array 16, pipettor 39 is dispensed to mixture all or part with mixture 21 and becomes droplet at inlet 11 places.Last step is to make drop 21 touch the solid wall of the single shrinkage pool 15 of microtiter plate 14.Mixture 21 droplets also can touch the liquid in the shrinkage pool 15 Already in.
With reference to figure 11-11A, pipette tip 10 can comprise the molded pore 22 that passes a wall, can use in the noncontact allocator.In this modification, external instrument provides the air source, and this air source enters pore 22, and forces mixture 21 to be discharged by inlet 11, enters microtiter plate 14.Be similar to molded recess, this molded pore 22 also can be used to measure the designated volume of source liquid.
With reference to figure 12-12A, pipette tip 10 can comprise the projection of similar capillary geometry, the perhaps variation of other inner molded feature 23, and it is used for capturing and keeping source liquid 17.
With reference to figure 13-13A, pipette tip 10 can comprise the feature 24 to the projection of the center of tip.This feature 24 can comprise very soft edge 25, makes it can not collect any liquid at little geometric space.This feature 24 comprises the metering recess 26 (or a plurality of recess) of capture source liquid (not shown).This notch width is w, and length is 1.
With reference to figure 14-14A, pipe 27 is shown as and comprises a plurality of recesses.In order to see more clearly in the drawings, pipe 27 is cut open along its center line, exposes its inner recess 28 and 29.The flute profile recess 28 of sealing adopts to capture with open flute profile recess 29 and keep the same mode of source liquid 29a and captures and keep source liquid 28a.Source liquid can flow along the direction of arrow 30, and returns along the direction of opposite arrow 31, stays the source liquid 28a and the 29a of accurate amount respectively in recess 28 and recess 29.In certain embodiments, source liquid can be limited liquid (slug), and can only flow along the direction of arrow 30, stays the source liquid 28a and the 29a of accurate amount after flowing through respectively in recess 28 and recess 29.
With reference to figure 15-15A, small pieces 32 are shown as and comprise a plurality of recesses.Small pieces 32 are for defining the plywood that a plurality of capillary channels come moving liquid.In case place on the small pieces, come process source liquid such as passage by small pieces, mix, cultivate, react, separate and detect required step.The motion of passing passage is controlled in uniting of working pressure and/or voltage.In order to see more clearly in the drawings, small pieces 32 are cut open along its center line, expose its inner recess 34 and 35.Capillary channel 33 is connected with inlet 36.The liquid-transfering device (not shown) that comprises active liquid (not shown) is connected with inlet 36.Liquid-transfering device moving source liquid passes inner recess 34 and 35, then liquid is discharged inlet 36.Inner recess 34 and 35 has comprised the source liquid (not shown) of accurate amount now.Liquid-transfering device is connected to the inlet 36 of small pieces 32 once more, and precipitates one glass of diluent liquid (not shown).The diluent liquid that liquid-transfering device will pass recess 34 and 35 moves forward and backward, thereby source liquid and diluent liquid are mixed.When liquid-transfering device and inlet 36 disconnections, definite mixture is stayed in the capillary channel.
In Figure 16, plate 37 is shown as and comprises a plurality of recesses 38.The device that comprises active liquid can affect the source liquid that passes recess 38, and stays the source liquid of fixed amount.Recess 38 length are 1, and wide is w, is d deeply.
With reference to figure 17-17A, pipette tip 10 includes continuous radial projection part 42, keeps feature as capillary.On jut, capture the also predetermined sample liquids that is measured 43 of retained dose by capillary force.In the pipette tip 10b of Figure 18-18A, the sample liquids that on a series of discontinuous juts 44, is measured by capillary force capture and retained dose.
Can be designed to compatible various liquid according to device of the present invention, comprise aqueous buffer, organic solvent, such as methyl-sulfoxide (DMSO), acid, alkali, protein, oligonucleotide and reagent.Compatibility is to reach by the element of selecting suitable material manufacturing to contact with liquid.The exemplary materials of making element is stainless steel, nylon, polyethylene, polypropylene, EPD rubber, silicon rubber and polytetrafluoroethylene (PTFE) (PTFE; Teflon
).Suitable material and element be fabricated to ordinary skill in this area.
Several embodiments of the present invention have more than been described.Yet, be appreciated that under the situation that does not break away from the spirit and scope of the present invention and can make many variations.Such as, inner recess can be superficial makings or chemistry or biological adherent, make that a spot of source liquid can be attached to the place of texture or adherent appearance, include any fine feature, extention or surface peening such as coarse processing, chemistry or biology (inner or outside), it is because capillary force, surface energy, gravity, chemical bond or biological combination (or above-mentioned all associatings) and can affect with liquid hold-up.Accordingly, other embodiment is in the scope of following claim.
Claims (43)
1. pipette comprises:
Elongated body (27), this body (27) has outer surface (112), and defines the inner passage of opening wide in described body lower end (106) (33,102);
Described body defines the opening (12) in this body top (108), and air can pass this opening (12) and be sucked out from described passage (33,102), the lower end (106) of liquid by described body is drawn in the passage (33,102);
Wherein, described body has the inwall (104) that defines the recess (13,26,28,29,34,35,38) that opens wide to inner passage (33,102), and the size of this recess (13,26,28,29,34,35,38) manufactures the liquid of being collected and keep the dosing that is inhaled into described passage (33,102) at passage (33,102) when finding time in addition.
2. pipette according to claim 1, wherein, described body comprises the detachable pipette tip (10) that defines recess (13,26,28,29,34,35,38).
3. pipette according to claim 2, wherein, described pipette tip (10) is formed by synthetic resin, and described recess (13,26,28,29,34,35,38) is that molded inner surface (104) by described tip limits.
4. according to each described pipette among the claim 1-3, wherein, described body also defines the pore (22) that extends to described inner passage (33,102) from described outer surface (112).
5. according to each described pipette among the claim 1-3, wherein, the size of described recess (13,26,28,29,34,35,38) manufactures the sample liquids (17) of the dosing of collected volume between 1 millilambda and 10 microlitres.
6. pipette according to claim 5, wherein, the volume of the sample liquids of described dosing (17) is between 5 millilambdas and 10 microlitres.
7. according to each described pipette among the claim 1-3, wherein, described recess (13,26,28,29,34,35,38) is arranged in the wide part of passage (33,102) that the openend (106) of the ratio body of inner passage (33,102) locates.
8. according to each described pipette among the claim 1-3, wherein, described recess (13,26,28,29,34,35,38) comprises the upwardly extending otch (13,26) that is limited in the described inner body wall (104), and/or the surface that limits the described pipette of extension degree under the described recess (13,26,28,29,34,35,38) is basically perpendicular to the longitudinal axis (110) of described body, and/or described recess (13,26,28,29,34,35,38) is elongated and is parallel to the longitudinal axis (110) of described body.
9. according to each described pipette among the claim 1-3, wherein, when the longitudinal axis that is parallel to described pipette (110) is measured, described recess (13,26,28,29,34,35,38) length (1) is between 0.01 to 1 inch (0.25 to 25 millimeter), and/or, when the RADIAL that extends along the longitudinal axis from described pipette is measured, described recess (13,26,28,29,34,35,38) width (w) is between 0.001 to 0.04 inch (0.025 to 1.02 millimeter), and/or described recess (13,26,28,29,34,35,38) the degree of depth (d) is between 0.001 to 0.100 inch (0.025 to 2.54 millimeter).
10. according to each described pipette among the claim 1-3, wherein, described body defines apart from one another by a plurality of described recess (13,26,28,29,34,35,38) that is provided with.
11. according to each described pipette among the claim 1-3, wherein, described recess (13,26,28,29,34,35,38) is limited in the projection (23) that extends in the described inner passage (33,102).
12. the sample liquids (17) of a use pipette metering doses according to claim 1 also mixes the method for this sample liquids (17) with diluent liquid (20), this method comprises:
Sample liquids (17) is incorporated in the described passage (33,102) that is limited in the housing (10), this housing defines the recess (13,26,28,29,34,35,38) that opens wide to passage (33,102), the size of this recess manufactures at the sample liquids (17) of passage (33,102) for collection dosing in empty, and keeps the dosage of collecting by capillary force;
Under the condition of the sample liquids (17) of the dosing of in can keeping recess (13,26,28,29,34,35,38), collecting, sample liquids (17) is removed from passage (33,102); And
Then, the diluent liquid (20) of certain volume is incorporated in the passage (33,102),, and this diluent liquid (20) and sample liquids (17) is mixed formation mixture (21) diluent liquid (20) diffusion.
13. method according to claim 12, wherein, described housing comprises pipette, and sample liquids (17) is incorporated into comprises in the passage (33,102) sample liquids is drawn in the pipette.
14. method according to claim 13, wherein, described pipette comprises pipette joint and pipette tip (10) movably, and sample liquids (17) removed from passage (33,102) comprise that mobile example liquid (17), this sample liquids (17) pass the recess (13) that is limited by the pipette tip.
15. method according to claim 14, wherein, described pipette tip (10) is formed by synthetic resin, and described recess (13) is that molded inner surface (104) by described tip limits.
16. method according to claim 12, also be included in sample liquids (17) removed from passage (33,102) after and in the diluent liquid (20) of introducing certain volume before,
Cleaning fluid is incorporated into the following position of described recess (13,26,28,29,34,35,38) in the passage (33,102); And
Then cleaning fluid is removed from passage (33,102), rinse out any residual sample liquid (17) from passage (33, the 102) surface below described recess (13,26,28,29,34,35,38).
17. according to each described method among the claim 12-15, wherein, described housing comprises passage (33,102) is limited to wherein pipe (27).
18 methods according to claim 17, wherein, this pipe (27) has open lower end (106), enters pipe (27) by imbitition, and sample liquids (17) passes this open lower end (106) and is introduced into.
19. method according to claim 17, wherein, than narrow on the top (108) of pipe (27), and/or described recess (13,26,28,29,34,35,38) is arranged in the wide part of the passage (33,102) of open end of ratio pipe (27) of passage (33,102) described passage (33,102) in the lower end (106) of pipe (27).
20. method according to claim 17, wherein, described recess (13,26,28,29,34,35,38) comprises the upwardly extending otch (13,26) that is limited in pipe (27) inwall (104), and/or described pipe (27) surface that limits extension degree under the described recess (13,26,28,29,34,35,38) is basically perpendicular to the longitudinal axis (110) of described pipe (27), and/or described recess (13,26,28,29,34,35,38) is elongated and is parallel to the longitudinal axis (110) of described pipe (27).
21. method according to claim 17, wherein, when being parallel to the longitudinal axis measurement of described pipe (27), described recess (13,26,28,29,34,35,38) length (1) is between 0.01 to 1 inch (0.25 to 25 millimeter), and/or when the RADIAL that extends along the longitudinal axis from described pipe (27) is measured, described recess (13,26,28,29,34,35,38) width (w) is between 0.001 to 0.04 inch (0.025 to 1.02 millimeter), and/or described recess (13,26,28,29,34,35,38) the degree of depth (d) is between 0.001 to 0.100 inch (0.025 to 2.54 millimeter).
22. method according to claim 18, wherein, than narrow on the top (108) of pipe (27), and/or described recess (13,26,28,29,34,35,38) is arranged in the wide part of the passage (33,102) of open end of ratio pipe (27) of passage (33,102) described passage (33,102) in the lower end (106) of pipe (27).
23. method according to claim 18, wherein, described recess (13,26,28,29,34,35,38) comprises the upwardly extending otch (13,26) that is limited in pipe (27) inwall (104), and/or described pipe (27) surface that limits extension degree under the described recess (13,26,28,29,34,35,38) is basically perpendicular to the longitudinal axis (110) of described pipe (27), and/or described recess (13,26,28,29,34,35,38) is elongated and is parallel to the longitudinal axis (110) of described pipe (27).
24. method according to claim 18, wherein, when being parallel to the longitudinal axis measurement of described pipe (27), described recess (13,26,28,29,34,35,38) length (1) is between 0.01 to 1 inch (0.25 to 25 millimeter), and/or when the RADIAL that extends along the longitudinal axis from described pipe (27) is measured, described recess (13,26,28,29,34,35,38) width (w) is between 0.001 to 0.04 inch (0.025 to 1.02 millimeter), and/or described recess (13,26,28,29,34,35,38) the degree of depth (d) is between 0.001 to 0.100 inch (0.025 to 2.54 millimeter).
25. according to each described method among the claim 12-15, wherein, described housing comprises plywood (32), and this plywood defines fluid passage (33,102), recess (13,26,28,29,34,35,38) and the inlet that contacts with described passage (33,102) fluid.
26. method according to claim 25, wherein, sample liquids (17) is pneumatically to be incorporated into passage (33,102) neutralization to remove from passage (33,102).
27. also comprise according to each described method among the claim 12-15, the mixture (21) of metered volume be assigned in the target shrinkage pool (15).
28. method according to claim 27, wherein, the distribution and computation volume comprises pneumatically promote mixture (21) from described housing, and/or promotes described mixture (21) by gas-pressurized from described housing.
29. according to each described method among the claim 12-15, wherein, described housing also limits pore (22) between described housing outer surface (112) and described passage (33,102).
30. method according to claim 29 wherein, enters described passage (33,102) and comes from described housing to promote described mixture (21) by forcing gas-pressurized to pass described pore (22).
31. according to each described method among the claim 12-15, wherein, the size of described recess (13,26,28,29,34,35,38) manufactures the sample liquids (17) of the dosing of collected volume between 1 millilambda and 10 microlitres.
32. method according to claim 31, wherein, the volume of the sample liquids of described dosing (17) is between 5 millilambdas and 10 microlitres.
33. according to each described method among the claim 12-15, wherein, the described volume that is incorporated into the diluent liquid (20) in the passage (33,102) is in the scope between 1 millilambda and 1 milliliter.
34. method according to claim 33, wherein, in the described scope of volume between 1 millilambda and 500 microlitres that is incorporated into the diluent liquid (20) in the passage (33,102).
35. according to each described method among the claim 12-15, wherein, described housing defines apart from one another by a plurality of described recess (13,26,28,29,34,35,38) that is provided with.
36. according to each described method among the claim 12-15, wherein, described recess (13,26,28,29,34,35,38) is by being that safe material constitutes to the material that forms described shell inner surface, and/or described recess (13,26,28,29,34,35,38) is limited in the projection (23) that extends in the described passage (33,102).
37. according to each described method among the claim 12-15, wherein, it is round mobile that described diluent liquid (20) is repeatedly passed described recess (13,26,28,29,34,35,38), and it is mixed with the sample liquids (17) of doses.
38., comprise sample liquids (17) is incorporated in the passage (33,102) of a plurality of pipettes of arranging with array (16) according to each described method among the claim 12-15.
39. according to the described method of claim 38, this method also comprises:
The mixture (21) of metered volume is assigned in the array (14) of liquid receiving element (15).
40. according to the described method of claim 39, wherein, the array of pipette (16) directly is arranged in the top of the array (14) of described liquid receiving element (15).
41. according to the described method of claim 40, wherein, the array (14) of described liquid receiving element (15) comprises porous container (14).
42. according to the described method of claim 41, wherein, described porous container is selected from the cohort of being made up of 96 hole microtiter plates, 384 hole microtiter plates and 1536 hole microtiter plates.
43. according to each described method among the claim 12-15, also comprise mixture (21) with metered volume be assigned on the slide or electronics calibrating reading device on.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US54489704P | 2004-02-17 | 2004-02-17 | |
| US60/544,897 | 2004-02-17 | ||
| US60/547,958 | 2004-02-27 | ||
| US10/911,845 | 2004-08-05 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1921944A CN1921944A (en) | 2007-02-28 |
| CN100434181C true CN100434181C (en) | 2008-11-19 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005800051996A Active CN100434181C (en) | 2004-02-17 | 2005-02-17 | Metering doses of sample liquids |
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| Country | Link |
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| CN (1) | CN100434181C (en) |
| ZA (1) | ZA200606771B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI20095230A0 (en) * | 2009-03-09 | 2009-03-09 | Thermo Fisher Scientific Oy | dilution Lace |
| CN101957273B (en) * | 2009-07-15 | 2012-09-19 | 英科新创(厦门)科技有限公司 | Device for collecting and diluting trace liquid sample at fixed ratio and use method thereof |
| CN105699121A (en) * | 2014-11-28 | 2016-06-22 | 宏达国际电子股份有限公司 | Micro-collector |
| CN105854969B (en) * | 2016-06-12 | 2017-08-29 | 齐齐哈尔医学院 | 5 50 microlitre of 60 suction nozzle pipettor |
| DE102016015700A1 (en) * | 2016-12-21 | 2018-06-21 | Bayer Pharma Aktiengesellschaft | metering |
| CN108786948A (en) * | 2018-06-19 | 2018-11-13 | 江苏科华医疗器械科技有限公司 | A kind of accurate trace liquid diluting pipettor |
| CN110694704B (en) * | 2019-09-26 | 2021-10-12 | 安徽省昂普拓迈生物科技有限责任公司 | Portable quick micro-droplet generator |
| TWD218529S (en) * | 2020-09-30 | 2022-05-01 | 富佳生技股份有限公司 | Graphical user interface for nucleic acid detector |
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| US6054325A (en) * | 1996-12-02 | 2000-04-25 | Glaxo Wellcom Inc. | Method and apparatus for transferring and combining distinct chemical compositions with reagents |
| US6130098A (en) * | 1995-09-15 | 2000-10-10 | The Regents Of The University Of Michigan | Moving microdroplets |
| US6451188B1 (en) * | 1997-06-06 | 2002-09-17 | Caliper Technologies Corp. | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
| US6488894B1 (en) * | 1997-11-19 | 2002-12-03 | Biognosis Gmbh | Device for sequential discharge of flowable reagents |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US6130098A (en) * | 1995-09-15 | 2000-10-10 | The Regents Of The University Of Michigan | Moving microdroplets |
| US6054325A (en) * | 1996-12-02 | 2000-04-25 | Glaxo Wellcom Inc. | Method and apparatus for transferring and combining distinct chemical compositions with reagents |
| US6451188B1 (en) * | 1997-06-06 | 2002-09-17 | Caliper Technologies Corp. | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
| US6488894B1 (en) * | 1997-11-19 | 2002-12-03 | Biognosis Gmbh | Device for sequential discharge of flowable reagents |
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| Publication number | Publication date |
|---|---|
| ZA200606771B (en) | 2008-09-25 |
| CN1921944A (en) | 2007-02-28 |
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