阅读说明：本技术 用于对生物样品进行超声处理的方法和装置 (Method and apparatus for being ultrasonically treated to biological sample ) 是由 P·H·罗彻尔 P·伯克纳 U·尼尔森 M·霍尔泽 于 2019-04-04 设计创作，主要内容包括：本公开文本涉及一种用于对生物样品进行超声处理的装置。简而言之,样品管支架可枢转地悬挂在超声处理装置的支座中,从而允许旋转自由度以及在超声波发生器与样品管之间的优化的接触面积。还公开了一种用于使用本文描述的装置对生物样品进行超声处理的方法。(The disclosure is related to a kind of device for being ultrasonically treated to biological sample.In brief, sample tube rack is pivotly suspended in the support of ultrasonic processing apparatus, to allow the contact area of rotary freedom and the optimization between supersonic generator and sample cell.Also disclose a kind of method for being ultrasonically treated using device described herein to biological sample.)

1. a kind of ultrasonic processing apparatus (10) is used for the packet in the sample cell (300) with essentially round side wall (310) The biological sample contained is ultrasonically treated, which includes:

Sample tube rack (100) is pivotly suspended in corresponding support (110), allows the sample tube rack (100) It is rotated in the vertical direction around x-axis (150), which is the rotation axis of pivot (130), wherein the sample Pipe holder (100) is configured as being maintained at the sample cell (300) along z-axis line (350) in the case where no rotary motion On vertical direction, which is substantially parallel to gravity direction and perpendicular to the x-axis (150), and the wherein sample cell Bracket (100) includes the opening (140) towards at least side；

Supersonic generator (200) comprising for ultrasonic wave to be applied to the sonication areas of the sample cell (300) (210), which includes concave surface and installs in itself and in the identical height of pivot (130), should X-axis (150) is substantially in the height at the vertical center (215) of the sonication areas (210), and wherein the ultrasonic wave occurs Device (200) be mounted on for along the y-axis (250) perpendicular to the x-axis (150) and the z-axis line (350) towards or away from this On the guide rail (220) of the mobile supersonic generator (200) of sample tube rack (100), wherein the sample tube rack (100) should Support (110) is fixed to one end of the guide rail (220), and wherein the opening (140) of the sample tube rack (100) is towards the ultrasound Processing region (210), so that in the sonication areas (210) and the sample tube rack (100) in ultrasonic treatment position The sample cell (300) side wall (310) physical contact；

Actuator (400) is used for along the y-axis (250) relative to the sample tube rack (100) in the guide rail (220) The mobile supersonic generator (200).

2. the ultrasonic processing apparatus (10) of claim 1, wherein the sample tube rack (100) is removable.

3. the ultrasonic processing apparatus (10) of any one of preceding claims, wherein the support of the sample tube rack (100) It (110) include anchoring base part (160) and rotatable portion (170), which includes the pivot (130) and be used for The substrate (171) of the sample tube rack (100) is kept, wherein the pivot (130) is pivotly to be suspended on the anchoring base portion Divide the hinge in the respective pivot bearing (161) of (160).

4. the ultrasonic processing apparatus (10) of any one of preceding claims, wherein the support of the sample tube rack (100) It (110) further include height adjuster (120), the height adjuster is for adjusting the sample in the sample tube rack (100) Manage the position of (300) in the z-axis line (350).

5. the ultrasonic processing apparatus (10) of any one of preceding claims, wherein the guide rail (220) includes slide plate.

6. the ultrasonic processing apparatus (10) of any one of preceding claims, wherein the actuator (400) is configured as super to this Sonic generator (200) applies variable force.

7. the ultrasonic processing apparatus (10) of claim 6, wherein the actuator (400) is configured as to the supersonic generator (200) apply the power of 10N, 50N, 100N or 500N to 750N, 1000N, 2500N or 5000N.

8. the ultrasonic processing apparatus (10) of claim 7, wherein the power is about 800N.

9. the ultrasonic processing apparatus (10) of any one of preceding claims, wherein the sample tube rack (100) is configured as protecting It holds multiple sample cells (300), and the sonication areas (210) includes having one or more subregions (211) with concave surfaces.

10. a kind of ultrasonic processing apparatus (10) for using any one of any one of claims 1 to 99 is to essentially round side The method that the biological sample for including in the sample cell (300) of wall (310) is ultrasonically treated, method includes the following steps:

A) sample cell (300) is inserted into the sample tube rack (100), and the sample tube rack (100) is inserted into the ultrasound In the corresponding support (110) of processing unit (10), wherein the sequence of these inserting steps is interchangeable；

B) by the supersonic generator (200) along the y-axis (250) and the guide rail (220) via actuator (400) direction The sample tube rack (100) is mobile, until the sonication areas (210) contacts the sample cell (300) by the opening (140) The side wall (310)；

C) will from the actuator (400) predefined power along the y-axis (250) via the supersonic generator (200) It is applied to the sample cell (300) and is therefore applied to the sample tube rack (100), so that the sonication areas (210) contacts The sample cell side wall (310) simultaneously pushes the sample cell (300) rotatable portion (170) of the sample tube rack (100) to Inner wall, thus by the sample cell (300) firmly fix and by by they with included by the sonication areas (210) The concave surface carries out centering to adjust its position along the x-axis (250), and the movement of the supersonic generator (200) is in the side wall (310) further such that the sample tube rack (100) is around this in the case where not being aligned with the surface of the sonication areas (210) X-axis (150) rotary motion leads to the sonication areas (210) and the sample cell side wall (310) until reaching stop point Between contact area increase；

D) by the contact area between the sonication areas (210) and the sample cell side wall (310) by ultrasonic wave from this Supersonic generator (200) is applied to the sample cell (300).

11. the method for claim 11, wherein the sample tube rack (100) is configured as keeping multiple sample cells (300), and And the sonication areas (210) includes having one or more subregions (311) with concave surfaces.

Technical field

The invention belongs to the analysis system fields for carrying out biology or biochemical measurement.In the art, it is related to By means of ultrasonication come the processing to liquid biological sample, such as the sample containing biomolecule.

Background technique

Primary biological sample (such as in the case where diagnosing in vitro) to be analyzed usually requires preparatory analysis processing, then Biochemistry or biological and physical analysis instrument etc. could be passed through to handle them.

For example, in the case where detecting pathogen, analytical reagent is to the intracorporal specific analyte of the cause of disease close to can be with It is realized by typical preparation step, virion or bacterial cell are cleaved so that corresponding content object is released in this step It puts, it then could be using the further measure for being enriched with discussed analyte.Most of common virus particles and bacterium are thin The Standard cleavage program of born of the same parents is generally acknowledged and is known to the skilled in the art.

However, certain pathogen need tightened up processing successfully to be cracked, including mycobacterium tuberculosis complex (MTBC) species are hereinafter also referred to as " mycobacteria ".These bacteriums are wrapped up by relatively thick and complicated cell wall, with It is compared in other most of their counterparts clinically found in relevant bacterium, shows considerably higher robustness.

Suspect that the sample containing mycobacteria (or other challenging biomaterials) can be by applying ultrasonic wave (also referred to as ultrasonic treatment or ultrasonication) is pre-processed.The approach is usually known in the art and establishes.So And in some cases, high efficiency of transmission of the ultrasonic wave from ultrasonic processing apparatus to sample may be difficult to achieve.One in this field A little approach are dependent on ultrasonic treatment, and the submergence of counter sample container is in liquid medium, is generally only in water.In such case Under, the vibration as caused by ultrasonic wave is actually transmitted to sample container and is therefore transmitted to internal sample by water, wherein one Divide main kinetic energy usually as thermal loss.More efficient approach is related to through the object between supersonic generator and corresponding container Ultrasonic energy is directly shifted in reason contact.Similarly, here, if contact surface between supersonic generator and the wall of sample container Product be not it is optimal, then may hinder energy transfer.

The relational approach applied in this field include such as US 6,686,195, it discloses control supersonic generator with The weight of degree of coupling between sample container.However, the surface of sample container is not usually ideal uniform, but show Certain tolerances based on material and/or production, these tolerances can reduce effective physical coupling and therefore reduce ultrasonic energy Transmission.

The disclosure describes a kind of approach for avoiding these disadvantages in this field.

Summary of the invention

Described herein in a first aspect, disclosing a kind of for carrying out ultrasound to the biological sample for including in sample cell The device of processing.The device includes at least sample tube rack, supersonic generator and actuator.

Sample tube rack is flexibly hung from the pivot for the support being joined in ultrasonic processing apparatus.Pivot allows pipe Bracket is rotated around x-axis in the vertical direction.As long as pipe holder does not have rotating and excursion, it will be along z-axis line by counter sample Pipe is maintained at vertical direction, and the z-axis line is substantially along gravity direction and perpendicular to x-axis, so that pipe and internal sample are It is substantially upright.Pan straddle has the opening at least side, to allow to be physically contacted between pipe and supersonic generator.

The latter includes sonication areas, will be ultrasonic by sonication areas when contacting its essentially round side wall Wave is transferred to sample cell.Supersonic generator is aligned with sample holder, so that the vertical center of sonication areas is (along z-axis Line) with rotation pivot point (being indicated by x-axis, sample tube rack can rotate about) it is in identical height.Supersonic generator It is mounted on guide rail, it is moved along y-axis towards or away from sample holder by means of actuator.The latter perpendicular to X-axis and z-axis line.In order to be ultrasonically treated, sonication areas can pass through the corresponding opening and sample cell in sample tube rack Side wall contact.The guidance to this movement is improved by the way that one end of guide rail to be fixed to the support of sample tube rack.If by In the inhomogeneities of the sidewall surfaces of pipe or in the case where tapered or conical tube wall, a part of tube wall is in tube wall It is contacted before other parts with sonication areas, then it can be scheduled by applying via supersonic generator to sample holder Power, by the contact of sonication areas (to optimize actual contact area, and to optimize the biography of ultrasonic wave It is defeated) Lai Yinqi sample cell and the therefore rotary motion of sample tube rack.The concave surface of sonication areas facilitates along x-axis Maximize contact area in a lateral direction.

As a further aspect, disclosed herein is a kind of for including in sample cell using above-mentioned apparatus The method that biological sample is ultrasonically treated.

Detailed description of the invention

Fig. 1 shows the perspective side elevation view of the embodiment of ultrasonic processing apparatus described herein (10), wherein ultrasonic wave Generator (200) is in the position far from sample tube rack (100) and in ultrasonic treatment position.

Fig. 2 depicts cross-sectional side view corresponding with the embodiment of Fig. 1.

Fig. 3 shows the perspective side elevation view for illustrating the rotary motion of sample tube rack (100).

Fig. 4 provides the viewgraph of cross-section of the diagram of Fig. 3.

Fig. 5 shows supersonic generator (200) each stage mobile towards sample tube rack (100), and will be right Sample cell (300) is visualized along the adjusting of x-axis (150).

Specific embodiment

First aspect described herein is a kind of ultrasonic processing apparatus, for in the sample with essentially round side wall The biological sample for including in pipe is ultrasonically treated, which includes:

Sample tube rack is pivotly suspended in corresponding support, allows the sample tube rack in the vertical direction It is rotated around x-axis, which is the rotation axis that pivot defines, and wherein the sample tube rack is configured as not having The sample cell is kept in the vertical direction along z-axis line in the case where having rotary motion, which is substantially parallel to gravity Direction and perpendicular to the x-axis, and wherein the sample tube rack includes the opening towards at least side；

Supersonic generator comprising for ultrasonic wave to be applied to the sonication areas of the sample cell, at the ultrasound Reason region includes concave surface and installs in height identical with the pivot in itself, and the x-axis is substantially in the ultrasonic treatment In the height at the vertical center in region, wherein the supersonic generator is mounted on for along perpendicular to the x-axis and the z-axis line Y-axis towards or away from the guide rail of the mobile supersonic generator of the sample tube rack, wherein the sample tube rack should Support is fixed to one end of the guide rail, and wherein the opening of the sample tube rack is towards the sonication areas, so that in super The sonication areas of sonication position and the side wall of the sample cell in the sample tube rack are physically contacted；

Actuator is used to move ultrasonic wave generation on the guideway relative to the sample tube rack along the y-axis Device.

This ultrasonic processing apparatus enables a technician to optimize from supersonic generator to the biology in counter sample pipe The transmission of the ultrasonic energy of sample, to effectively handle it, such as to crack the strong cause of disease of such as mycobacteria Body simultaneously discharges its biochemical content object, such as nucleic acid.

The interaction for the supersonic generator that the sample tube rack pivotly hung is controlled with power allows geometry flexible Property, compensate for the variation in the surface of sample cell side wall or on surface.

Caused by it may be the tolerance in production process for example due to pipe in the non-uniform situation of tube wall, at ultrasound Contact area between reason region can reduce as previously alluded, so as to pipe and therefore biological sample thereto Energy transfer may be hindered.In ultrasonic processing apparatus described herein, in the rotary motion of not sample tube rack In the case where, the sample cell substantially vertically kept along z-axis line may have slightly unequal or warpage surface.It can replace For ground or additionally, pipe be can have towards its top or more commonly towards the tapered of its bottom in some embodiments Shape.For example, pipe can have cone shape in some embodiments.

In the case where this or similar, the side wall of sample cell may not form ideal plane.More precisely, edge The vertical dimension of sample tube wall contacted with sonication areas, certain parts on surface can be prominent relative to other parts It rises.In the case where the sample tube rack rigidly installed, when supersonic generator is moved to sample tube rack, ultrasonic treatment Region will press against on tube wall, and can not adjust position or orientation.In the lesser situation of applied force, sonication areas is only Tube wall is contacted at one or more protrusion, leads to non-optimal contact area and correlation energy transmission loss.Another party Face, in the biggish situation of applied force, supersonic generator may be such that pipe deforms, this may jeopardize the integrality of sample cell.Afterwards A kind of situation possibly even leads to the loss of specimen material, the pollution including ultrasonic processing apparatus, and certain in biological sample Security risk is caused to operator in the case where containing pathogen.

However, ultrasonic processing apparatus described herein is optimized at the side wall and ultrasound of sample cell by providing geometric flexibility The contact area between region is managed to avoid these risks.More precisely, in these cases, leaned against with predefined force Supersonic generator on side wall will not be such that sample tube rack is maintained in the construction for causing contact area to reduce, but sample cell branch Frame can be when the sonication areas of tube wall and supersonic generator be contacted around the x-axis rotation limited by the pivoting point of pivot Turn.For example, if pipe has the tapered shape towards its bottom and is vertically retained in sample tube rack, vertically , substantially uniform sonication areas will usually contact the top of tube wall first.Via supersonic generator from actuating When device applies predefined power to tube wall, pipe can star rotary motion now, and wherein the top of its contact follows ultrasonic wave to send out The movement of raw device, and lower part (at present not in contact with) is rotated towards sonication areas, the movement with supersonic generator on the contrary, because It is mounted in substantially the same height for the vertical center of sonication areas and by the pivoting point that x-axis indicates.As a result, side The top of wall will keep being physically contacted with sonication areas, and lower part (previously not in contact with) will be rotated towards sonication areas And it is touched, to optimize the possible contact area between tube wall and sonication areas.In this position, " at ultrasound Manage position ", the rotary motion of sample tube rack and the translational motion of supersonic generator all reach stop point, as long as so that from Supersonic generator is applied to sample cell and is therefore applied to the power of sample tube rack and keeps constant, and is just entirely being ultrasonically treated The contact area of optimization is kept in the process.However, if being contacted when the side wall primary of sonication areas and sample cell contacts Area be it is optimal, then can also be reached in the case where no rotary motion ultrasonic treatment position.

Term

Terms used herein " ultrasonic treatment " refer to the physical vibration for converting the electrical signal to and being directed toward biological sample The process of (being ultrasonic wave in this case).Ultrasonic wave generator is produced as the primary signal of energy converter power supply.In some realities It applies in scheme, signal has the frequency from 20kHz, 35kHz or 50kHz to 75kHz, 100kHz or 250kHz.In some implementations In scheme, frequency is about 20kHz.Via intermediary element (such as the piezo-electric crystal that can be stacked above in supersonic generator Crystal), this signal is converted into mechanical oscillation, which is referred to as converting.Supersonic generator can be such as metal The bar of bar, and it can be for example with cylindrical or cone.The frequency of electric current be can choose as supersonic generator Resonant frequency, so that the latter utilizes standing wave extensional vibration at its resonant frequency.Vibration can be amplified by such as booster, then Sample cell is transmitted to via the transmission unit on the ultrasonic treatment surface for including supersonic generator.Ultrasonic treatment face it is quick Movement generates ultrasonic wave, by the biological sample migration in sample cell, causes the pressure change for growing and collapsing.It is corresponding dynamic The biomaterial in sample can be used to handle, such as so as to lytic cell, such as other of mycobacteria or clinical interest to be thin Born of the same parents or virus.

" supersonic generator ", which generally includes to be attached to the one of tapered metallic rod, laminates electric transducer.Other suitable materials Material and shape are known to the skilled in the art.The end use application of bar is in work materials.The exchange vibrated at ultrasonic frequencies Electricity is applied to PZT (piezoelectric transducer) by individual power supply unit.Electric current makes them expand and shrink.

In meaning of the present disclosure, " biological target material " or " biomaterial " includes various biomolecule, such as Protein or nucleic acid, and there are also other naturally occurring molecules or its derivatives or synthetic analogues or variant.In addition, art Language " biomaterial " includes virus and eukaryocyte and prokaryotic cell.In some embodiments, biological target material is nucleic acid, Such as DNA, RNA or PNA.DNA can be such as viral DNA, genomic DNA or Plasmid DNA.Biological target material can be day It is right or modification.It is primary compared with the DNA or RNA that corresponding naturally occurring biomaterial is for example separated from organism Biomaterial will not irreversibly change.The biomaterial of modification includes biotinylated molecule, such as nucleic acid or protein etc..

As used herein, refer to may be potentially containing the biomaterial of analytes of interest analytes for term " biological sample ".In " biological sample " is in the embodiment of " liquid biological sample ", and sample can come from any biological source, such as physiology sample, Including blood, saliva, crystalline body fluid, cerebrospinal fluid, sweat, urine, excrement, sperm, vaginal secretion, milk, ascites, mucus, synovia, Peritoneal fluid, amniotic fluid, tissue, culture cell, sputum etc..Test sample can be pre-processed using preceding, such as be prepared from blood Blood plasma, dilution viscous fluid are totally diluted, crack.Processing method can be related to filtering, distillation, concentration, interfering component Inactivation and reagent addition.Biological sample can be when obtaining directly using or pretreatment to modify the spy of sample from source It is used after sign.In some embodiments, original solid or semisolid biomaterial can be incited somebody to action by using suitable liquid medium It dissolves or suspends and be rendered as liquid.In some embodiments, suspect that biological sample contains certain antigen or nucleic acid.

" sample cell " refers to the container for being configured as keeping biological sample.Sample cell usually has top and bottom, wherein Bottom is usually closed, and top then includes the opening for introducing or removing sample, reagent etc..Opening can be by for example may be used The lid of removal seals.Suitable lid is that technical staff is known and including nut, molding or press-fitting cap, sealing foil etc.. As used herein, sample cell has generally elongated shape, such as cylindrical, cone or analogous shape.It include bottom wall and Side wall.Multiple side walls that the latter can be a continuous side walls or be separated by angle.The interior surface of sample cell is usually inertia , so that it will not interfere the analysis for example occurred in pipe or preparative to chemically react.For device disclosed herein and side Sample cell in method usually has the length from 2cm, 3.5cm or 5cm to 10cm, 15cm or 20cm.In some embodiments, Length from bottom to top is about 7.5cm.In some embodiments, (side wall to side wall) width or diameter be from 0.5cm, 1cm or 1.5cm are to 2cm, 3.5cm, 5cm, and in a more particular embodiment, it is about 1cm.

" sample tube rack " refers to the device for receiving sample cell.Sample tube rack can be single-tube support or multitube branch Frame.Multitube bracket includes the shelf for example for 2,3,4,5,10 or more pipes.In some embodiments, sample tube rack With for being inserted into sample cell and holding it in the slot of specific position.In context described herein, sample tube rack sheet It is when sample cell is inserted into that sample cell is fixed in particular directions in matter.The rotating and excursion of not sample tube rack the case where Under, sample cell is kept vertical position in itself by sample tube rack.In some embodiments, sample cell is formed assembly In sample tube rack, to provide close fit on fixed-direction.

In context described herein, " pivotly hang " mean the object that sample tube rack such as can be removed with Rotary freedom is joined to another object (such as corresponding support).Sample tube rack described herein can be hung at it from support When around as pivoting point x-axis rotation.

Sample tube rack described herein is removable in some embodiments, wherein " removable " means that it can With the separation of its corresponding support, without destroying any one of two components.For example, sample tube rack may include hinge Chain, it includes the corresponding bearing for allowing rotary freedom simultaneously which, which can neatly be joined to by corresponding support,.For example, right It, can be and being detached from the hinge of sample tube rack bearing corresponding to support after the sample discussed is ultrasonically treated Sample tube rack is removed from support and ultrasonic processing apparatus.Therefore, sample tube rack can be transferred to such as biochemical analysis Instrument or analysis module.In addition, sample cell can be filled outside ultrasonic processing apparatus when keeping via sample tube rack, be made It is standby or otherwise handle, thus not only simplify workflow again and reduce due in such as ultrasonic processing apparatus sample or The spilling of reagent and cause pollution risk.

In some embodiments, the support of sample tube rack includes two parts, is even wrapped in some embodiments Include more than two part.In a more particular embodiment, the support of sample tube rack includes anchoring base part and rotatable Part, rotatable portion include pivot and the substrate for keeping sample tube rack, and wherein pivot is pivotly to be suspended on admittedly Determine the hinge in the respective pivot bearing of base part.

The advantages of this two-piece type arrangement of support include for example, if rotatable portion shows signs of wear, then can be with This part is removed and replaced without influencing anchoring base part.Therefore, it is permanent to can be used as its essential part by the latter Ground is fixed on the bottom of ultrasonic processing apparatus.

In order to Optimization for Ultrasonic Wave generator sonication areas with sample cell (when the sample being present in its corresponding support When in quality control bracket) in include biological sample alignment, the support of ultrasonic processing apparatus disclosed herein is in some embodiment party It include height adjuster in case, the height adjuster is for adjusting position of the sample cell in z-axis line in sample tube rack. In this way, due to the effect of gravity, biological sample is especially the liquid or partially liq sample for being contained mainly in bottom of the tube The height of the sonication areas of the supersonic generator in ultrasonic treatment position can be reached.This can be to avoid ultrasonic treatment The case where region contact has no or only a part of tube wall that seldom sample is positioned, which may make the ultrasonic treatment of sample It is more difficult.For adjust the sample cell in sample tube rack height device include for example spring, coil, screw mechanism, Air buffer, actuator etc..In some embodiments, height adjuster is manually operable.In other embodiments In, height adjuster includes automechanism.

" guide rail " of ultrasonic processing apparatus described herein can be implemented by any suitable structure, which is super Movement of the sonic generator on the direction of restriction provides guidance.In the simplest case, guide rail is straight (one-dimensional) structure, Supersonic generator is moved back and forth along the structure by actuator.However, in appropriate circumstances, guide rail can also extend across Second or third dimension.For example, two or more sample tube racks being mounted adjacent can benefit from branch point Guide rail, allow supersonic generator by be separately directed to its correspond to support in each sample tube rack because answering It is such with that may need.Guide rail can include the frame of suspension supersonic generator in some embodiments.Equally some In embodiment, guide rail can be implemented by the tunnel of holding supersonic generator.In some embodiments, described herein super The guide rail of acoustic processing device includes slide plate.In a more particular embodiment, slide plate is mounted on railing and carries at the top of it Supersonic generator.

Ultrasonic processing apparatus described herein may include control unit and/or Data Management Unit.

The mode of " control unit " control automatic system is that the steps necessary of processing protocol is executed by automatic system.This meaning Control unit can for example indicate that automatic system pipettor executes certain liquid relief steps with by liquid biological sample and reagent Mixing or control unit control automatic system are to be sometime incubated for biological sample or reagent or both at a certain temperature Mixture or control unit control ultrasonic processing apparatus described herein supersonic generator precise motion or its He moves or relevant parameter.Control unit can from Data Management Unit (DMU) receive about need to some sample execute which The information of a little steps.In some embodiments, control unit can be integrated with Data Management Unit, or can be by Common hardware is implemented.For example, control unit may be embodied as the programmable logic controller (PLC) of operation computer-readable program, the meter Calculation machine readable program is provided with the instruction that operation is executed according to process operation planning.Specifically, control unit may include adjusting Device is spent, for executing the series of steps of such as above-mentioned movement in the given time.Control unit can be according to type, tight Anxious degree etc. further determines that the sequence of sample to be processed.Control unit can also be from detection relevant to the measurement of the parameter of sample Unit receives data.

" Data Management Unit " is the computing unit for storage and management data.This may relate to and will be by automatic system The relevant data of the fluid sample of processing, or to relevant data the step of execution by ultrasonic processing apparatus described herein.Number It may be coupled to LIS (laboratory information system) and/or HIS (hospital information system) according to administrative unit.Data Management Unit (DMU) can be unit in the automatic system interacted or with automatic system unit positioned jointly.It may be control A part of unit processed.Alternatively, DMU can be the unit far from automatic system positioning.For example, it can be via network It is connected in the computer of automatic system and implements.

In order to supersonic generator starting sample tube rack around the restriction of x-axis rotation, control and (if necessary Words) the adjustment power of sample cell that is applied to supersonic generator from actuator and is therefore applied in its respective holder may be It is advantageous.

Therefore, in some embodiments of ultrasonic processing apparatus described herein, actuator is configured as to ultrasonic wave Generator applies variable force.In some embodiments, actuator be configured as to supersonic generator apply 10N, 50N, The power of 100N or 500N to 750N, 1000N, 2500N or 5000N.In a more particular embodiment, power is about 800N.

For example, controlling if to handle different types of sample tube rack in same ultrasonic processing apparatus and changing this A power may be advantageous.For example, the quality based on sample tube rack, it may be necessary to which increased power starts the rotation around x-axis Transhipment is dynamic, and reset force may be bigger than in the case where lighter sample tube rack.In addition it is possible to use different types of sample Quality control, some of them type can have the structure more exquisite than other types.Therefore, reduction applied force may be useful, So as not to can damage more pressure-sensitive pipe type integrality.

For the benefit of parallelization and increase flux, ultrasonic processing apparatus described herein can be configured as primary support With the more than one sample cell of processing.This may require carrying out certain adjustment to sample tube rack and/or supersonic generator, wherein It is some to be disclosed herein exemplary implementation scheme.

Therefore, in some embodiments of ultrasonic processing apparatus described herein, sample tube rack is configured as keeping Multiple sample cells, and sonication areas includes having one or more subregions with concave surfaces.In some embodiments, surpass Sonication region includes the tool sub-district with concave surfaces of the identical quantity of the quantity for the sample cell being configured to keep with sample tube rack Domain.

Other aspect of the present disclosure is a kind of for using ultrasonic processing apparatus disclosed herein to this The method that the biological sample for including in the sample cell of circular side wall in matter is ultrasonically treated, method includes the following steps:

A) sample cell is inserted into sample tube rack, and sample tube rack is inserted into the corresponding support of ultrasonic processing apparatus In, wherein the sequence of these inserting steps is interchangeable；

B) supersonic generator is moved via actuator towards sample tube rack along y-axis and guide rail, until ultrasound The side wall that processing region passes through opening contact sample cell；

C) the predefined power from actuator is applied to sample cell and therefore via supersonic generator along y-axis It is applied to sample tube rack, so that sonication areas contacts sample cell side wall and sample cell is pushed to the inner wall of sample tube rack Or its rotatable portion, so that sample cell be firmly fixed and by by concave surface included by they and sonication areas Centering is carried out to adjust its position along x-axis, the movement of supersonic generator side wall not with the surface of sonication areas Further such that sample tube rack leads to ultrasonic treatment zone until reaching stop point around x-axis rotary motion in the case where alignment Contact area between domain and sample cell side wall increases；

D) ultrasonic wave is applied from supersonic generator by the contact area between sonication areas and sample cell side wall It is added to sample cell.

About step a), as previously mentioned, in some embodiments in the sample tube rack outside ultrasonic processing apparatus Preparing sample cell may be advantageous.For example, multiple sample cells can be put into multitube sample tube rack and for example by reality Room personnel are tested to pre-process manually.Such step may relate to (be with or without examination to multiple sample cell adding liquid biological samples Agent), and covered for the latter.In the next step, by the way that by sample tube rack engagement, to corresponding support, lab assistant can be with Easily all pretreated sample cells in same sample pipe holder are put into ultrasonic processing apparatus.This is conducive to entire work Make process, and can lead to the turnaround time of shortening.Alternatively, sample tube rack can be put into ultrasonic processing apparatus first In.As embodiment, one in previously described multiple pipes is needed replacing, or needs to add additional pipe, it then can be with Sample tube rack is stayed in into (other pipes will be ultrasonically treated) inside ultrasonic processing apparatus, and single pipe can be replaced or Addition.

In the case where ultrasonic processing apparatus as described herein, according to the type adjustment of sample cell and/or sample tube rack Predefined power in step c) may be advantageous.

In some embodiments of method described herein, step a) further includes the sample cell adjusted in sample tube rack Height.

Equally in some embodiments of method described herein, sample tube rack is configured as keeping multiple samples Pipe, and sonication areas includes having one or more subregions with concave surfaces.The advantages of this embodiment includes increasing Flux, as combined described in ultrasonic processing apparatus disclosed herein.

As described above, the on the one hand sample in sample cell and on the other hand sonication areas is vertically-aligned for sample It is advantageous for the ultrasonic treatment efficiency of middle biomaterial.Accordingly, by the concave surface of sonication areas or its subregion, It is laterally aligned to be also such.

The every other specific embodiment of method disclosed herein is also applied for device disclosed herein.

Exemplary implementation scheme

Following embodiment is intended to illustrate the specific embodiment of literary the methods and apparatus disclosed, and they are not restricted 's.

The schematic diagram of Figure 1A depicts the perspective side elevation view of the embodiment of ultrasonic processing apparatus disclosed herein (10).In In the present embodiment, in order to preferably check other component, one or more sample cells (300) and sample tube rack is omitted (100).It is the corresponding support (110) of sample tube rack between the component shown in.Support (110) in the present embodiment includes Anchoring base part (160) and rotatable portion (170), the rotatable portion include substrate (171), which is used for this In the case of keep tool there are five independent sample cell (300) sample tube rack (100).Rotatable portion (170) is also wrapped in two sides It includes pivot (130), the pivoting point of the pivot limits x-axis (150), rotatable portion (170) and therefore sample tube rack (100) it can be rotated around x-axis in insertion.Pivot (130) (depicted here as hinge) by support anchoring base part (160) Respective pivot bearing (161) keep.The rotatable portion (170) of the present embodiment further has height adjuster (120), The height adjuster is the manually operable mechanism based on screw (120) in the depicted case, for being promoted or being reduced Keep the substrate (171) of sample tube rack (100).Therefore in the present embodiment, entire sample holder can be adjusted vertically (100), so that at sample cell (300) and the adjustable ultrasound to supersonic generator (200) of biological sample wherein included Manage the height of region (210).Go to the latter, it can be seen that the sonication areas (210) of the present embodiment includes five sub-districts Domain (211) is used for the maximum load of five independent sample cells (300).This sonication areas of supersonic generator (200) (210) opening (140) of the side towards sample tube rack (100, be not shown), allows the sonication areas by opening Mouth (140) and one or more sample cells (300) are physically contacted.The guide rail of the supersonic generator (200) of the present embodiment (220) include slide plate (221), supersonic generator (200) are installed on slide plate, and slide plate (221) itself is via connector (222) railing (223) are installed to.This guide rail (220) arrangement provides supersonic generator (200) along y-axis (250) Mobility.As can be seen that this mobility is one-dimensional, so that supersonic generator (200) can be by means of actuator (400) support (110) towards or away from sample tube rack (100) is mobile, and one end of guide rail (220) is fixed on the support (110) it on, is fixed on its anchoring base part (160) in the present embodiment.Support (110) and z-axis line (350) are substantially It is in alignment with, and is substantially parallel to gravity direction.It can also be seen that the ultrasound of embodiment shown here in this description The compound of wave producer (200).Piezoelectric element is included in converter (201), and primary electronic signal is converted into mechanical oscillation. Before subsequent transmission unit (203) transmits energy via its sonication areas (210), mechanical oscillation are by subsequent enhancing Device (202) amplification.

Figure 1B shows the ultrasonic processing apparatus (10) of Figure 1A in ultrasonic disposal site.Supersonic generator direction The sample tube rack (100) being installed in the rotatable portion (170) of corresponding support (110) is mobile.With its each sub-regions (211) sonication areas (210) passes through opening (140) accordingly and the sample cell being maintained in sample tube rack (100) (300) it contacts.

Fig. 2A is gone to, the ultrasonic processing apparatus (10) of present Fig. 1 is depicted as cross-sectional side view.Sonication areas (210) be mounted on pivot (130) height of the same nature at.It can also be seen that the vertical dimension of sonication areas (210) Degree, together with its vertical center (215), this is centrally mounted at height identical with the pivoting point limited by x-axis (150) vertically Place.

As shown in Figure 1B, the ultrasonic treatment in the cross-sectional side view to Fig. 2A is shown in the ultrasonic treatment position of Fig. 2 B The description of device (10).

Fig. 3 and Fig. 4 is provided using such as the sheet for the ultrasonic processing apparatus as described herein (10) described in shown in aforementioned The diagram of the embodiment of the method for text description.

Fig. 3 A shows the perspective side elevation view of the embodiment above of ultrasonic processing apparatus described herein (10).In order to more The support (110) for checking the sample tube rack (100) with insertion well, has been omitted from guide rail (220).Such as Figure 1A and Fig. 2 B institute Show, supersonic generator (200) is remotely located, the side of sonication areas (210) and sample cell (300) in this position Wall does not have direct physical contact between (310).In contrast with aforementioned diagram, the rotatable portion (170) of support (110) is opposite It is slightly slanted in z-axis line (350), this can be checked in more detail in the respective cross section side view of Fig. 4 A.

The configuration of the ultrasonic processing apparatus (10) of the present embodiment in ultrasonic treatment position is shown in Fig. 3 B and Fig. 4 B Out.It is applied while the sonication areas (210) of supersonic generator (200) is contacted with the side wall (310) of sample cell (300) When adding predefined power, the part of side wall (310) is located above the vertical center (215) of sonication areas (210), and because This pivotally the pivoting point of (130) x-axis (150) around x-axis (150) counterclockwise rotate.Since sample cell (300) is close It is internal that ground is assemblied in sample tube rack (100), and sample tube rack is fitted snugly within the rotatable portion of corresponding support (110) Divide (170) internal, rotatable portion (170) follows this rotary motion of sample cell (300), until reaching current Fig. 3 B and figure Stop point shown in 4B.In the ultrasonic treatment position that the present embodiment generates, sample cell (300) is vertical, and because This is parallel to z-axis line (350).This is because caused by following situations: the side wall of sample cell shown in Fig. 3 and Fig. 4 (300) (310) any substantive inhomogeneities, and sonication areas (the 210) (packet of supersonic generator (200) are not shown Include ultrasonic treatment subregion (211)) it is parallel to z-axis line (350) alignment.Therefore, the sample cell in sample tube rack (100) (300) and the vertical position of the rotatable portion (170) of support (110) indicates such position: at this location, sample cell side Wall (310) and sonication areas (210) have optimum contact area, so that ultrasonic energy (kinetic energy) be promoted to occur from ultrasonic wave Device (200) arrives effective transfer of biological sample.In the embodiment being shown here at, it means that each individual subregion (211) it is contacted with the side wall (310) of each corresponding sample cell (300).

The diagram of Fig. 5 A- Fig. 5 C provides further showing to the mechanism for adjusting sample cell (300) along x-axis (150) Show, showing sample tube rack (100) from all angles, (in the embodiment of description, more precisely its is rotatable Partially (170)).

Fig. 5 A depict the transmission unit (203) of the supersonic generator (200) with sonication areas (210) with when Between sequence towards sample tube rack (100) movement.The rotatable portion (170) of sample tube rack (100) is viewed from above be as Cross section at the seen height limited by plane " A " of Fig. 5 B.

First description stage of the movement is as shown in Fig. 5 A (i).It is including five different ultrasonic treatments subregion (211) The present embodiment in, sonication areas (210) has been positioned at distance in the rotatable portion of sample tube rack (100) (170) short distance of the side wall (310) of the sample cell (300) kept in.As can be seen that most of sample cells (300) do not have It is aligned along x-axis (150) with their corresponding ultrasonic treatments subregion (211).It goes to Fig. 5 A (ii), is ultrasonically treated subregion (211) it is physically contacted with the side wall (310) of corresponding sample cell (300).Subregion (211) are ultrasonically treated by means of the recessed of them Face makes center movement of the sample cell (300) along x-axis (150) towards each respective sub-areas (211), this is at Fig. 5 A (iii) Description in further spread out.By continuing to predefined power, the ultrasonic wave with transmission unit (203) occurs Device (200) is mobile towards sample tube rack (100) along y-axis (250), and spill ultrasonic treatment subregion (211) to have The sample cell (300) of its essentially round side wall (310) realizes sliding motion.As can be seen that embodiment shown herein relates to And the support component (171) of the interior rear wall protrusion from the rotatable portions (170) of sample tube rack (100).The performance of these protrusions The concave surface similar with the ultrasonic treatment surface of subregion (211) out, and help to be directed at sample cell (300) in the x direction.So And being ultrasonically treated the concave surface of subregion (211) can also be realized pair and sample cell (300) is pressed against in the plane of rear wall It is quasi-.Therefore, in some embodiments, rear wall does not include support component shown herein (171).It is reached eventually in Fig. 5 A (iv) Point, sample cell (300) is aligned along x-axis (150) with their corresponding ultrasonic treatments subregion (211) herein.This field The skilled person will understand that sonication areas (210) is not necessarily as described herein as each ultrasonic treatment of support Implement on the surface in region (211).For example, sonication areas (210) can have a subregion without any protrusion (211) single concave surface can for example be arranged for engagement single sample pipe (300).In some embodiments, it props up The rotatable portion (170) of seat (110) can flexibly be hung, so that providing one or more freedom degrees, rotatable portion (170) the optimally aligned of related component is potentially contributed to the freedom degree.