DE202013102432U1 - pipetting - Google Patents

Abstract

A pipetting apparatus (1) comprising: a) a block (2) for holding a plurality of identically formed pipette tips (3) having a tip axis (4) and connecting said pipette tips (3) to a plurality of pipette cones (5) of a multi-pipette head ( 6) a liquid handling apparatus (7), the block (2) comprising: i) a plurality of cavities (8) penetrating the block (2) arranged in parallel with each other; ii) a plurality of at a bottom (9) of the block (2) arranged and a lower opening of the cavities (8) forming, cylindrical insertion openings (10) which are designed for frictionally receiving a respective pipette tip (3) that the Tip axes (4) of all inserted pipette tips (3) are arranged substantially parallel to each other; and iii) a plurality of conical insertion openings (13) arranged on an upper side (12) of the block (2) and forming an upper opening of the cavities (8), each for sealingly inserting a pipette cone (5) of a multi - pipette head (6 ) is trained; b) a plurality of tubular pipette tips (3) each having a wall (14) extending along the tip axis (4) and having a transport opening (15) located at a front end for receiving and dispensing liquid samples; and c) means (20) for connecting block (2) and multiple pipette head (6); characterized in that the pipetting device (1) further comprises: d) a plurality of receptacles (16) extending concentrically with the tip axes (4) and penetrating the block (2), each having a shoulder (17); and e) a plurality of inserts (18) extending concentrically with the tip shafts (4) for insertion into the receptacles (16) of the block (2), each insert (18) having a cavity (8), a cylindrical insertion opening (10 ) with inserted pipette tip (3) and a conical insertion opening (13) for sealingly inserting a pipette cone (5) of a multi-pipette head (6), wherein each insert (18) has a support (19), with which it in the block (2) inserted on the shoulder (17) of the corresponding receptacle (16) rests.

Description

The invention relates to a pipetting device according to the preamble of claim 1. Such pipetting devices typically comprise a block for holding a plurality of identically formed pipette tips having a tip axis and for connecting these pipette tips to a plurality of pipette cones of a multi-pipette head of a liquid handling apparatus. Such a block comprises a plurality of cavities penetrating the block, which are arranged parallel to one another. Often, these cavities are arranged in an array corresponding to the array of wells of a standard microplate. Such a block also comprises a plurality of cylindrical insertion openings arranged on a lower side of the block and forming a lower opening of the cavities. These insertion openings are designed for the frictional reception of a respective pipette tip such that the tip axes of all inserted pipette tips are substantially parallel to each other, e.g. in such an array. In this case, each cylindrical insertion opening may preferably have a stop which is designed to act on a rear end of a pipette tip inserted. Such a block further comprises a plurality of conical insertion openings arranged on an upper side of the block and forming an upper opening of the cavities, each of which is designed to sealably insert a pipette cone of a multi-pipette head. In addition, such a pipetting device typically comprises a number of tubular pipette tips each having a wall extending along the tip axis and having a forward opening transport port for receiving and dispensing liquid samples and means for connecting the block and multiple pipette head. Such devices may include, for example, holding apertures with holding shafts for receiving holders attached to the multiple pipette head.

Standardized standard microplates (cf., eg Standard ANSI_SBS 1-2004 ) are known and have arrays of wells arranged, for example, at a center distance of 9 mm (96 well microplate) or 4.5 mm (384 well microplate).

When performing more complex series of experiments or assays, so-called wall effects sometimes occur in microplates, i. In the outermost wells of a 96-well microplate, deviating results from the middle wells may occur. Therefore, standards and controls are often given in wells located in middle rows or columns of a microplate. However, to process these pipetting patterns is very complicated and time-consuming and can also be carried out, e.g. when using 96-well microplates, are not operated with a multi-pipette head and a conventional 96-well block; usually an 8-channel pipettor is used. In conventional blocks having a plurality of e.g. 96 or 384 pipette tips, no particular portions of the entire tip array can be used without e.g. Pipette tips not belonging to these arrays are more or less brutally removed in "rebuilt blocks". Thus, it happens that a first "rebuilt block" is used to pipette the standards, a second "rebuilt block" to pipette the controls, and a third "rebuilt block" to pipette the samples into the arrays provided. If several of the 96 or 384 pipette tips or even a single pipette tip of a 96 or 384-channel block is damaged by a collision with a labware article (e.g., a microplate), these pipette tips must be laboriously replaced by a service specialist.

It is an object of the present invention to provide an alternative pipetting apparatus having a block for holding a plurality of identically formed pipette tips, which eliminates prior art disadvantages of conventional blocks.

• a) einen Block zum Halten einer Vielzahl von identisch ausgebildeten Pipettenspitzen mit einer Spitzenachse und zum Verbinden dieser Pipettenspitzen mit einer Vielzahl von Pipettenkonen eines Mehrfachpipettenkopfs einer Liquidhandlingapparatur, wobei der Block umfasst: i) eine Vielzahl den Block durchdringender Hohlräume, die parallel zueinander angeordnet sind; ii) eine Vielzahl von an einer Unterseite des Blocks angeordneter und eine untere Öffnung der Hohlräume bildender, zylindrischer Einsetzöffnungen, die derart zur reibschlüssigen Aufnahme je einer Pipettenspitze ausgebildet sind, dass die Spitzenachsen aller eingesetzten Pipettenspitzen im Wesentlichen parallel zueinander angeordnet sind; und iii) eine Vielzahl von an einer Oberseite des Blocks angeordneter und eine obere Öffnung der Hohlräume bildender, konischer Einstecköffnungen, von denen jede zum dichtenden Einführen eines Pipettenkonus eines Mehrfachpipettenkopfes ausgebildet ist;
• b) eine Anzahl von rohrförmigen Pipettenspitzen mit je einer sich entlang der Spitzenachse erstreckenden Wand und mit einer an einem vorderen Ende angeordneten Transportöffnung zum Aufnehmen und Abgeben von Flüssigkeitsproben; und
• c) Einrichtungen zum Verbinden von Block und Mehrfachpipettenkopf.

This object is achieved with a pipetting device according to the combination of features of independent claim 1. This pipetting device comprises:

• a) a block for holding a plurality of identically formed pipette tips having a tip axis and for connecting these pipette tips to a plurality of pipette cones of a multi-pipette head of a liquid handling apparatus, the block comprising: i) a plurality of block-penetrating cavities arranged parallel to each other; ii) a plurality of arranged on a bottom of the block and a lower opening of the cavities forming, cylindrical insertion openings, which are designed for frictionally receiving a respective pipette tip, that the tip axes of all inserted pipette tips are arranged substantially parallel to each other; and iii) a plurality of tapered insertion apertures disposed on an upper surface of the block and forming an upper opening of the cavities, each of which is adapted for sealingly inserting a pipette cone of a multi-pipette head;
• b) a plurality of tubular pipette tips each having a wall extending along the tip axis and having a transport opening located at a forward end for receiving and dispensing liquid samples; and
• c) Devices for connecting block and multiple pipette head.

• d) eine Vielzahl von sich konzentrisch zu den Spitzenachsen erstreckender, den Block durchdringender Aufnahmen, von denen jede einen Absatz aufweist; und
• e) eine Vielzahl von sich konzentrisch zu den Spitzenachsen erstreckender Einsätze zum Einstecken in die Aufnahmen des Blocks, wobei jeder Einsatz einen Hohlraum, eine zylindrische Einsetzöffnung mit eingesetzter Pipettenspitze und eine konische Einstecköffnung zum dichtenden Einführen eines Pipettenkonus eines Mehrfachpipettenkopfes umfasst, wobei jeder Einsatz eine Auflage aufweist, mit welcher er im Block eingesetzt auf dem Absatz der entsprechenden Aufnahme aufliegt.

The pipetting device according to the invention is characterized in that it additionally comprises:

• d) a plurality of block-penetrating receivers extending concentrically to the tip axes, each having a shoulder; and
• e) a plurality of inserts extending concentrically to the tip axes for insertion into the receptacles of the block, each insert comprising a cavity, a cylindrical insertion opening with inserted pipette tip and a conical insertion opening for sealingly inserting a pipette cone of a multi-pipette head, each insert having a support has, with which he rests in the block rests on the shoulder of the corresponding receptacle.

It is especially preferred that each insert with all-sided, horizontal play is located in the corresponding receptacle of the block. It is particularly preferred that the pipette tips, and thereby also the cavities, are arranged in an array that corresponds to the arrangement of wells of a standard microplate. In addition, it is preferred that each cylindrical insertion opening has a stop which is designed to act on a rear end of a pipette tip inserted.

• f) eine Rückhaltevorrichtung zum Verhindern eines ungewollten Herausziehens eines Einsatzes aus einer Aufnahme, beim Trennen von Block und Mehrfachpipettenkopf.

Preferably, the pipetting device according to the invention additionally comprises:

• f) a retaining device for preventing unwanted extraction of an insert from a receptacle, when separating block and multiple pipette head.

• – Unterschiedlichste Arrays von Pipettenspitzen können mit demselben Block frei konfiguriert und wieder verändert werden, so dass beliebige Muster von Well-Verteilungen in Mikroplatten bearbeitet werden können.
• – Defekte oder verstopfte Pipettenspitzen können durch jedermann einfach ausgebaut und durch neue Pipettenspitzen ersetzt werden.
• – Die erfindungsgemässe Pipettiervorrichtung kann zum Pipettieren von Assays mit Standards und Kontrollen verwendet werden, was insbesondere in Screening-Assays in der Biotechnologie und in der pharmazeutischen Industrie interessant ist.
• – Im Compound-Management in grossen Pharma-Firmen können diese frei konfigurierbaren Fixed-Tip-Blöcke zum Herstellen von Mutter- und Tochterplatten verwendet werden.
• – Waschbare, frei-konfigurierbare Fixed-Tip-Blöcke stellen eine kostensparende Konkurrenz zur Verwendung von entsprechend vielen Einwegpipettenspitzen bzw. Wegwerfpipettenspitzen dar.

Advantages of the pipetting device according to the invention include:

• - A wide variety of pipette tip arrays can be freely configured and resized with the same block, allowing any pattern of well distributions to be processed in microplates.
• - Defective or clogged pipette tips can be easily removed by anyone and replaced with new pipette tips.
• - The pipetting device according to the invention can be used for pipetting assays with standards and controls, which is particularly interesting in screening assays in biotechnology and in the pharmaceutical industry.
• - In compound management in large pharmaceutical companies, these freely configurable fixed-tip blocks can be used to fabricate parent and daughter plates.
• Washable, free-configurable fixed-tip blocks provide cost-saving competition to using a correspondingly large number of disposable pipette tips or disposable pipette tips.

Known and inventive pipetting devices are described in more detail with reference to exemplary embodiments illustrated in schematic drawings, these drawings are not intended to limit the scope of the disclosure. Show it:

1 a view of a known from the prior art multiple pipette head;

2 a vertical partial section through a known from the prior art block for holding identically formed pipette tips;

3 a vertical partial section through a block according to the invention for holding identically formed pipette tips;

4 an enlarged view of the vertical section of 3 ;

5 a simplified representation of 3 after removing the multiple pipette head and its pipette cones;

6 a simplified representation of 3 after removing the multiple pipette head and its pipette cones when lifting the lid;

7 an insert with pipette tip after lifting out of the block of 3 ;

8th an empty shot of the block from 3 ,

The 1 shows a view of a known from the prior art multiple pipette head 6 a liquid handling apparatus 7 , Such, known from the prior art liquid handling apparatus 7 includes a pipetting device 1 , This pipetting device 1 includes a block 2 (see. 2 ) for holding a plurality of identically formed pipette tips 3 with a tip axis 4 and for connecting these pipette tips 3 with a variety of pipette cones 5 a multiple pipette head 6 this liquid handling apparatus 7 , Such liquid handling apparatus are known, for example under the trade name "FREEDOM EVO ^®" and are produced by the current applicant and sold.

The 2 shows a vertical partial section through a block known from the prior art 2 for holding identically formed pipette tips 3 , The known from the prior art block 2 a variety includes the block 2 penetrating cavities 8th which in this case are arranged in parallel in an array corresponding to the arrangement of wells of a standard microplate.

This block 2 also includes a variety of on a bottom 9 of the block 2 arranged and a lower opening of the cavities 8th forming, cylindrical insertion openings 10 , These insertion holes 10 are so for frictional recording ever a pipette tip 3 formed that the top axles 4 all pipette tips used 3 are arranged substantially parallel to each other in this array. In this case, each cylindrical insertion opening 10 a stop 11 which is for applying to a rear end of a pipette tip inserted 3 is trained. By positively applying the stop 11 in the cylindrical insertion opening 10 will ensure that the transport openings 15 the pipette tips 3 , all of which have exactly the same length within the dimensional accuracy of the production process, lie in one plane. This can be done with a liquid handling robot (not shown) of the liquid handling apparatus 7 an exact elevation of the transport openings 15 all pipette tips 3 during pipetting (especially during aspiration) of liquids can be adjusted.

Notwithstanding the just described insertion could the pipette tips 3 all of exactly the same length within the dimensional accuracy of the manufacturing process by means of a gauge frictionally engaged in a cylindrical insertion opening 10 be sunk, no stop 11 having.

This block 2 further includes a plurality of on a top side 12 of the block 2 arranged and an upper opening of the cavities 8th forming, conical insertion openings 13 , Each of these conical plug-in openings 13 is for sealing insertion of a pipette cone 5 a multiple pipette head 6 (see. 1 ) educated. The pipette cone 5 typically includes a seal 5 ' which is usually elastically deformed sealingly against a conical insertion opening 13 is applied.

Such, known from the prior art pipetting device 1 also includes a number of tubular pipette tips 3 with one each along the tip axis 4 extending wall 14 and with a transport opening located at a front end 15 for receiving (aspirating) and dispensing (dispensing) of fluid samples.

Such, known from the prior art pipetting device 1 also includes facilities 20 to connect block 2 and multiple pipette head 6 , An exemplary device 20 is in the 1 and 2 shown. This device 20 includes holding openings 20 ' with holding axes 21 for picking up at the multiple pipette head 6 fastened holding devices 22 ,

The 3 shows in a to the 2 comparable enlargement a vertical partial section through a block according to the invention 2 for holding identically formed pipette tips 3 , An inventive pipetting device 1 includes at least one such block 2 for holding a plurality of identically formed pipette tips 3 with a tip axis 4 and for connecting these pipette tips 3 with a variety of pipette cones 5 a multiple pipette head 6 a liquid handling apparatus 7 , Preferably, each pipette cone comprises 5 a seal 5 ' , which is designed to penetrate the pipette cone 5 in a conical insertion opening 13 elastically deformed and sealing at this conical insertion openings 13 is applied.

The inventive block 2 a variety includes the block 2 penetrating cavities 8th arranged in parallel in an array corresponding to the array of wells of a standard microplate. The inventive block 2 also includes a variety of on a bottom 9 of the block 2 arranged and a lower opening of the cavities 8th forming, cylindrical insertion openings 10 , These cylindrical insertion openings 10 are so for frictional recording ever a pipette tip 3 formed that the top axles 4 all pipette tips used 3 are arranged substantially parallel to each other in this array. At a block 2 the example of the Standard ANSI_SBS 1-2004 adapted, are the top axles 4 the pipette tips 3 in an orthogonal grid with a lattice constant of 9 mm (for 96-well microplates) or with a lattice constant of 4.5 mm (for 384-well microplates). Is the block 2 adapted to another standard for microplates, so the arrangement of the tip axes 4 the pipette tips 3 according to that norm. In any case, each of the cylindrical insertion openings 10 preferably a stop 11 for applying to a rear end of an inserted pipette tip 3 is trained.

The inventive block 2 further includes a plurality of on a top side 12 of the block 2 arranged and an upper opening of the cavities 8th forming, conical insertion openings 13 each of which is for sealingly inserting a pipette cone 5 a multiple pipette head 6 is trained.

An inventive pipetting device 1 also includes a number of tubular pipette tips 3 with one each along the tip axis 4 extending wall 14 and with a transport opening located at a front end 15 for picking up and dispensing liquid samples. An inventive pipetting device 1 also includes facilities 20 to connect block 2 and multiple pipette head 6 , These facilities 20 can hold openings 20 ' with holding axes 21 for picking up at the multiple pipette head 6 fastened holding devices 22 include or otherwise configured.

An inventive pipetting device 1 also includes a plurality of preferably arranged in this array and concentric with the peak axes 4 extending, the block 2 penetrating recordings 16 each of which has a paragraph 17 having. An inventive pipetting device 1 also includes a plurality of arrays preferably arranged in this (one norm) array and concentric with the peak axes 4 extending missions 18 to plug in the recordings 16 of the block 2 , This includes every use 18 a cavity 8th , a cylindrical insertion opening 10 with inserted pipette tip 3 and a conical insertion opening 13 for sealing insertion of a pipette cone 5 a multiple pipette head 6 , Every use 18 has a circulation 19 on with which he is in the block 2 used on the heel 17 the corresponding recording 16 rests.

The 4 shows an enlarged view of the vertical section of 3 , whereby the individual elements of the inventive pipetting device 1 are better to recognize.

Every use 18 is preferably with allseitigem, horizontal play in the appropriate recording 16 of the block 2 , Preferably, as shown, the pipette tips 3 , and thereby the cavities 8th arranged in an array corresponding to the array of wells of a standard microplate. Preferably, each of the inserts 18 as an injection-molded plastic part and each tubular pipette tip 3 designed as a metal cannula. Preferably, as shown, each cylindrical insertion opening 10 a stop 11 for applying to a rear end of an inserted pipette tip 3 is trained.

When disconnecting from block 2 and multiple pipette head 6 Must have the static friction of up to 96 or 384 seals 5 ' the pipette cones 5 a used multiple pipette head 7 be overcome. Because it is particularly preferred that each insert with all-sided, horizontal play in the appropriate recording 16 of the block 2 would be, if separating block 2 and multiple pipette head 6 all existing bets 18 from the block 2 lifted. This lifting out of the pipette tips 3 from the block 2 can be tolerated or not. Should this lifting the pipette tips 3 from the block 2 be prevented, so must either the stiction of each seal 5 ' or the sum of all seals present 5 ' counteracted when the block 2 from the multiple pipette head used 6 should be disconnected. For this reason, the pipetting device according to the invention comprises 1 preferably a restraint device 23 for preventing accidental withdrawal of an insert 18 from a recording 16 when disconnecting block 2 and multiple pipette head 6 ,

In a first, preferred embodiment of the pipetting device 1 is the restraint device 23 as a lid 24 trained (cf. 3 ). Here is the lid 24 so on the block 2 with inserted inserts 18 fixable, that each of these inserts 18 with all-round, horizontal and vertical play in the corresponding recording 16 of the block 2 is held. This lid 24 includes a variety of openings 25 in the same array as the recordings 16 of the block 2 are arranged. In addition, each of these openings 25 as with a pipette cone 5 a multiple pipette head 6 freely punctiform designed.

In a second embodiment of the pipetting device 1 is the restraint device 23 as a rib / groove combination 26 . 27 educated. In a first variant, each of the inserts comprises 18 an at least partially circumferential rib 26 and each of the shots 16 of the block 2 includes a corresponding at least partially circumferential groove 27 , In this groove 27 snap the rib 26 one in the block 2 used insert 18 and thus holds this mission 18 without play in the appropriate recording 16 of the block 2 (see right side in 3 ). In a second variant, each of the inserts comprises 18 an at least partially circumferential groove 27 and each of the shots 16 of the block 2 includes a corresponding at least partially circumferential rib 26 , In this groove 27 one in the block 2 used insert 18 snap the rib 26 and thus holds this mission 18 without play in the appropriate recording 16 of the block 2 ,

As a major difference of the two embodiments of the restraint device 23 may be mentioned that in the first embodiment with lid 24 the pipette tips 3 only by the piercing of the pipette cone 5 into the conical insertion opening 13 be aligned in parallel in the precise array. In contrast, the pipette tips 3 in the second embodiment with rib / groove combination 26 . 27 by the mutual snap of rib 26 and groove 27 aligned parallel in the precise array.

Preferably, the shots 16 of the block 2 for inserting the pipette tips 3 graduated several times, the paragraph 17 forming a first stage and a second stage 28 near the bottom 9 of the block 2 is arranged. In particular, it is preferred that the paragraph 17 inside the block 2 arranged at a level that is closer to the top 12 as at the bottom 9 of the block 2 Because a greater distance between the first and second stages stabilizes the orientation of the insert 18 and thus the orientation of the pipette tip 3 effect.

Preferred is a first variant of the images 16 of the block 2 in which each of the shots 16 three cylindrical holes 29 . 29 ' . 29 '' includes. In this case, a first cylindrical bore extends 29 with a first diameter 30 from the top 12 of the block 2 to the paragraph 17 , a second cylindrical bore 29 ' with a second diameter 31 from the paragraph 17 to the second stage 28 and a third cylindrical bore 29 '' with a third diameter 32 from the second stage 28 up to the bottom 9 of the block 2 , It is also preferred that every use 18 a first, second and third maximum diameter 39 . 40 . 41 has (see center of 3 ; the maximum diameters are marked with thicker double arrows and the corresponding reference numerals are printed in bold).

• – der erste maximale Durchmesser 39 an (bzw. nahe) der Oberfläche 12 des Blocks 2 um das Doppelte eines ersten Frei- bzw. Spaltmasses 33 kleiner als der erste Durchmesser 30 der ersten zylindrischen Bohrung 29;
• – der zweite maximale Durchmesser 40 am Absatz 17 des Blocks 2 um das Doppelte eines zweiten Frei- bzw. Spaltmasses 34 kleiner als der zweite Durchmesser 31 der zweiten zylindrischen Bohrung 29’; und
• – der dritte maximale Durchmesser 41 an der zweiten Stufe 28 des Blocks 2 um das Doppelte eines dritten Frei- bzw. Spaltmasses 35 kleiner als der dritte Durchmesser 32 der dritten zylindrische Bohrung 29’’.

After inserting the insert 18 in the block 2 is:

• - the first maximum diameter 39 at (or near) the surface 12 of the block 2 twice the amount of a first clearance or gap 33 smaller than the first diameter 30 the first cylindrical bore 29 ;
• - the second maximum diameter 40 at the heel 17 of the block 2 twice the size of a second clearance or gap 34 smaller than the second diameter 31 the second cylindrical bore 29 '; and
• - the third maximum diameter 41 at the second stage 28 of the block 2 twice the size of a third clearance or gap 35 smaller than the third diameter 32 the third cylindrical bore 29 '' ,

In a second variant of the recordings 16 of the block 2 includes each of the shots 16 two cylindrical holes 29 . 29 '' , In this case, a first cylindrical bore extends 29 from the top 12 of the block 2 to the paragraph 17 and another cylindrical bore 29 '' from the second stage 28 up to the bottom 9 of the block 2 , In addition, each of the images includes 16 of the block 2 a conical bore 38 from the paragraph 17 to the second stage 28 enough. It is also preferred that every use 18 a first, second and third maximum diameter 39 . 40 . 41 having.

• – der erste maximale Durchmesser 39 an (bzw. nahe) der Oberfläche 12 des Blocks 2 um das Doppelte eines ersten Frei- bzw. Spaltmasses 33 kleiner als der erste Durchmesser 30 der ersten zylindrischen Bohrung 29;
• – der zweite maximale Durchmesser 40 am Absatz 17 des Blocks 2 um das Doppelte eines zweiten Frei- bzw. Spaltmasses 34 kleiner als der zweite Durchmesser 31 der konische Bohrung 38; und
• – der dritte maximale Durchmesser 41 an der zweiten Stufe 28 des Blocks 2 um das Doppelte eines dritten Frei- bzw. Spaltmasses 35 kleiner als der dritte Durchmesser 32 der weiteren zylindrischen Bohrung 29’’.

After inserting the insert 18 in the block 2 is (as on the left side of 4 shown):

• - the first maximum diameter 39 at (or near) the surface 12 of the block 2 twice the amount of a first clearance or gap 33 smaller than the first diameter 30 the first cylindrical bore 29 ;
• - the second maximum diameter 40 at the heel 17 of the block 2 twice the size of a second clearance or gap 34 smaller than the second diameter 31 the conical bore 38 ; and
• - the third maximum diameter 41 at the second stage 28 of the block 2 twice the size of a third clearance or gap 35 smaller than the third diameter 32 the further cylindrical bore 29 '' ,

A pipetting device is preferred 1 in which the lid 24 below the openings 25 cylindrical holes 36 includes that in the same array as the openings 25 of the lid 24 are arranged. In this case, the cylindrical holes 36 of the lid 24 preferably the same diameter as the first cylindrical bores 29 of the block 2 , These cylindrical holes 36 of the lid 24 face everyone in a reception 16 of the block 2 enclosed insert 18 a vertical free measure 37 ready. This free mass can range from a few hundredths to a few tenths of a millimeter, making sure that on the block 2 fixed (eg screwed on) lid 24 each of these inserts 18 with all-sided, horizontal and especially with vertical play in the appropriate recording 16 of the block 2 is held.

The preferred mass for a 96 block is in the following ranges (manufacturing tolerances are not considered): First diameter 30 8.09 mm Second diameter 31 6.61 mm Third diameter 32 5.85 mm First free or gap measure 33 0.07 mm Second clearance or gap 34 0.08 mm Third free or gap measure 35 0.05 mm Vertical free measure 37 0.10 mm First maximum diameter 39 7.95 mm Second maximum diameter 40 6.45 mm Third maximum diameter 41 5.75 mm.

Preferably, the pipetting device 1 also one or more blind inserts 42 (see left side of 4 ) for insertion into selected recordings 16 of the block 2 include. Each involves blanketing 42 a cavity 8th , an open cylindrical insertion hole 10 without inserted pipette tip 3 and a conical insertion opening 13 for sealing insertion of a pipette cone 5 a multiple pipette head 6 , In addition, each assigns dummy use 42 an edition 19 on with which he is in the block 2 used on the heel 17 the corresponding recording 16 rests. It is especially preferred that each dummy insert 42 with all-round, horizontal play in the corresponding recording 16 of the block 2 lies.

As material for the block 2 AlMg0.4Mn0.7 is preferred. As material for the inserts 18 and for the blind inserts 42 Polyetheretherketone (PEEK) is preferred. As material for the pipette tips 3 Stainless steel is preferred.

The 5 shows a simplified representation of 3 after removing the multiple pipette head 6 and its pipette cones 5 , The as a retention device 23 trained, here screwed to the block (not shown) cover 24 the pipetting device 1 has successfully prevented when disconnecting block 2 and multiple pipette head 6 one or more inserts 18 from their recordings 16 were pulled out. This lid 24 is preferably on the block 2 with inserted inserts 18 fixable, that each of these inserts 18 with all-sided, horizontal play (which is preferably twice the first clearance or gap 33 corresponds) and vertical play (the free measure 37 ) in the corresponding recording 16 of the block 2 is held. This includes the lid 24 a variety of openings 25 in the same array as the recordings 16 of the block 2 are arranged. In addition, each of these openings 25 as with a pipette cone 5 a multiple pipette head 6 freely punctiform designed.

The 6 shows a simplified representation of 3 after removing the multiple pipette head 6 and its pipette cones 5 when lifting the lid 24 , The individual bets 18 can now easily and without effort from the shots 16 of the block 2 be lifted. This lifting can be done with an instrument that takes the shape and mass of a pipette cone 5 having. Such an instrument (not shown) can be manually or with a robot of a liquid handling apparatus 7 (not shown) are moved and used to very specific operations 18 with damaged pipette tips 3 or selected inserts with possibly undamaged pipette tips from the block 2 to remove.

In a method for removing pipette tips 3 from a block 2 a pipetting device according to the invention 1 , which also has a lid 24 as a restraint device 23 to prevent one unwanted pulling out of an insert 18 from a recording 16 when disconnecting block 2 and multiple pipette head 6 includes, the multiple pipette head 6 and its pipette cones 5 from the block 2 separated, the lid 24 from the block 2 lifted and selected bets 18 be from the appropriate shots 16 lifted.

The 7 shows a bet 18 with pipette tip 3 after lifting out of the picture 16 of the block 2 from 3 , Particularly visible in this illustration are the first, second and third maximum diameters 39 . 40 . 41 of the insert 18 marked with thicker double arrows and with the corresponding reference numerals in bold. The cavity 8th is located in the interior of this insert and has an upper part to the top axis 4 concentric, conical insertion opening 13 on. Well visible here are the preferably circumferential edition 19 of the insert 18 as well as with its rear end up to the stop 11 inserted into the cylindrical insertion opening pipette tip 3 the pipetting device according to the invention 1 ,

The 8th shows an empty shot 16 of the block 2 from 3 , The first, second and third diameters are particularly clearly visible in this illustration 30 . 31 . 32 the first, second and third cylindrical bore 29 . 29 ' . 29 '' the recording 16 , Well visible here are the preferably circumferential paragraph 17 the recording 16 as well as the second stage 28 near the bottom 9 of the block 2 the pipetting device according to the invention 1 , Clearly visible is the difference between the course of the conical bore 38 (left) and the second cylindrical bore 29 ' (middle) in the block 2 ,

• 1. Der Deckel 24 wird vom Block (2) abgehoben und ausgewählte Einsätze 18 mit deren Pipettenspitzen 3 werden aus den entsprechenden Aufnahmen 16 des Blocks 2 herausgehoben. Dieser Ansatz wird bevorzugt, wenn die meisten Einsätze 18 verwendet und folglich nur wenige Einsätze 18 aus dem Block 2 entfernt werden sollen. Dabei wird vorzugsweise von einem vollständig bestückten Block 2 ausgegangen. Beispiele derartiger Verwendungen sind das Freistellen von Wells für Standards oder Kontrollen.
• 2. Der Deckel 24 wird vom Block (2) abgehoben und ausgewählte Einsätze 18 mit deren Pipettenspitzen 3 werden in bestimmte Aufnahmen 16 des Blocks 2 eingesetzt. Dieser Ansatz wird bevorzugt, wenn nur wenige Einsätze 18 verwendet und in einen leeren Block 2 eingesetzt werden sollen. Beispiele derartiger Verwendungen sind das Bereistellen von Pipettenspitzen zum Zugeben von Standards oder Kontrollen in bestimmten Wells von Standardmikroplatten.

Basically, there are two methods for providing pipette tips 3 in a block 2 a pipetting device according to the invention 1 at which the pipette tips 3 , and thereby the cavities 8th to be arranged in an array corresponding to the array of wells of a standard microplate, and in which the pipetting device 1 also a lid 24 as a restraint device 23 for preventing accidental withdrawal of an insert 18 from a recording 16 when disconnecting block 2 and multiple pipette head 6 includes:

• 1. The lid 24 is removed from the block ( 2 ) and selected bets 18 with their pipette tips 3 be from the appropriate shots 16 of the block 2 lifted. This approach is preferred when most inserts 18 used and therefore only a few bets 18 from the block 2 should be removed. It is preferably of a fully populated block 2 went out. Examples of such uses are the deletion of wells for standards or controls.
• 2. The lid 24 is removed from the block ( 2 ) and selected bets 18 with their pipette tips 3 be in certain shots 16 of the block 2 used. This approach is preferred when only a few bets 18 used and in an empty block 2 should be used. Examples of such uses are providing pipette tips for adding standards or controls to certain wells of standard microplates.

The empty shots 16 can each with blind inserts 42 be populated, so that with a conventional multiple pipette head 6 a liquid handling apparatus 7 certain wells can be served and other wells of the same microplate can be bypassed in a pipetting step. If necessary, complete with 96 or 384 inserts 18 and correspondingly many pipette tips 3 equipped block 2 and an empty block 2 with an identical array of shots 16 , Like features have been given like reference numerals, even though these features are known in the art or pertain to the invention, and although not all details are described in every case. In each of these reference numerals in the description of the 1 to 4 detailed reference. In the 5 to 7 For the sake of clarity, not all reference numbers are entered.

The detailed explanations of the block 2 and the inserts 18 were in relation to a version with 96 pipette tips 3 discussed for the use of standard microplates according to the Standard ANSI_SBS 1-2004 are arranged. Analogous and correspondingly smaller in the relevant dimensions, these statements also apply to blocks 2 and inserts 18 , which are designed to use standard 384 well microplates.

LIST OF REFERENCE NUMBERS

1

pipetting

2

block

3

pipette tip

4

tip axis

5

pipette barrel

5 '

Seal of 5

6

Multiple pipette head

7

Liquid Handling Equipment

8th

cavity

9

Bottom of the block

10

cylindrical insertion openings

11

attack

12

Top, surface of the block

13

conical insertion opening

14

wall

15

transport opening

16

admission

17

Sales of 16

18

commitment

19

Edition of 18 . 42

20

Device for connecting 2 & 6

20 '

holding opening

21

holding axis

22

holder

23

Restraint

24

cover

25

opening

26

rib

27

groove

28

second step

29

first cylindrical bore

29 '

second cylindrical bore

29 ''

third, additional cylindrical bore

30

first diameter

31

second diameter

32

third diameter

33

first free measure, gap size

34

second free measure, gap size

35

third free mass, gap

36

cylindrical bore of 23 / 24

37

vertical free measure

38

conical bore

39

first maximum diameter

40

second maximum diameter

41

third maximum diameter

42

blind insert

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited non-patent literature

• Standard ANSI_SBS 1-2004 [0002]
• Standard ANSI_SBS 1-2004 [0027]
• Standard ANSI_SBS 1-2004 [0053]

Claims (17)

Pipetting device ( 1 ), comprising: a) a block ( 2 ) for holding a plurality of identically formed pipette tips ( 3 ) with a tip axis ( 4 ) and for connecting these pipette tips ( 3 ) with a multiplicity of pipette cones ( 5 ) of a multiple pipette head ( 6 ) a liquid handling apparatus ( 7 ), whereby the block ( 2 ) comprises: i) a plurality of the block ( 2 ) penetrating cavities ( 8th ) which are arranged parallel to each other; ii) a plurality of on a lower side ( 9 ) of the block ( 2 ) and a lower opening of the cavities ( 8th ) forming, cylindrical insertion openings ( 10 ), which for frictional recording each a pipette tip ( 3 ) are formed such that the tip axes ( 4 ) of all inserted pipette tips ( 3 ) are arranged substantially parallel to each other; and iii) a plurality of on a top side ( 12 ) of the block ( 2 ) and an upper opening of the cavities ( 8th ) forming, conical insertion openings ( 13 ), each of which is for sealingly inserting a pipette cone ( 5 ) of a multiple pipette head ( 6 ) is trained; b) a number of tubular pipette tips ( 3 ) with one each along the tip axis ( 4 ) extending wall ( 14 ) and with a arranged at a front end of the transport opening ( 15 ) for receiving and dispensing liquid samples; and c) facilities ( 20 ) to connect block ( 2 ) and multiple pipette head ( 6 ); characterized in that the pipetting device ( 1 ) includes: d) a plurality of concentric with the peak axes ( 4 ) extending the block ( 2 ) penetrating recordings ( 16 ), each of which has a paragraph ( 17 ) having; and e) a plurality of concentric with the peak axes ( 4 ) extending inserts ( 18 ) for insertion into the recordings ( 16 ) of the block ( 2 ), whereby each use ( 18 ) a cavity ( 8th ), a cylindrical insertion opening ( 10 ) with inserted pipette tip ( 3 ) and a conical insertion opening ( 13 ) for sealingly inserting a pipette cone ( 5 ) of a multiple pipette head ( 6 ), each use ( 18 ) an edition ( 19 ), with which he in the block ( 2 ) used on the heel ( 17 ) of the corresponding recording ( 16 ) rests. Pipetting device ( 1 ) according to claim 1, characterized in that each insert with allseitigem, horizontal play in the corresponding receptacle ( 16 ) of the block ( 2 ) lies. Pipetting device ( 1 ) according to claim 1 or 2, characterized in that the pipette tips ( 3 ), and thereby also the cavities ( 8th ) are arranged in an array corresponding to the array of wells of a standard microplate Pipetting device ( 1 ) according to one of claims 1 to 3, characterized in that each of the inserts ( 18 ) as an injection-molded plastic part and each tubular pipette tip ( 3 ) is designed as a metal cannula. Pipetting device ( 1 ) according to one of the preceding claims, characterized in that each cylindrical insertion opening ( 10 ) a stop ( 11 ), which is for applying to a rear end of a pipette tip inserted ( 3 ) is trained. Pipetting device ( 1 ) according to one of the preceding claims, characterized in that the pipetting device ( 1 ) further comprises: f) a restraint device ( 23 ) for preventing an unwanted extraction of an insert ( 18 ) from a recording ( 16 ), when separating block ( 2 ) and multiple pipette head ( 6 ). Pipetting device ( 1 ) according to claim 6, characterized in that the retaining device ( 23 ) as a lid ( 24 ) is formed, wherein the lid ( 24 ) so on the block ( 2 ) with inserted inserts ( 18 ) is fixable that each of these inserts ( 18 ) with all-sided, horizontal and vertical play in the corresponding recording ( 16 ) of the block ( 2 ), the lid ( 24 ) a plurality of openings ( 25 ) in the same array as the images ( 16 ) of the block ( 2 ) are arranged, and wherein each of these openings ( 25 ) than with a pipette cone ( 5 ) of a multiple pipette head ( 6 ) is formed free pierceable. Pipetting device ( 1 ) according to claim 6, characterized in that the retaining device ( 23 ) as a rib / groove combination ( 26 . 27 ), each of the inserts ( 18 ) an at least partially circumferential rib ( 26 ) and each of the recordings ( 16 ) of the block ( 2 ) a corresponding at least partially circumferential groove ( 27 ) into which the rib ( 26 ) one in the block ( 2 ) used Use ( 18 ) snaps and so this use ( 18 ) without play in the corresponding recording ( 16 ) of the block ( 2 ) holds. Pipetting device ( 1 ) according to one of the preceding claims, characterized in that the recordings ( 16 ) of the block ( 2 ) for inserting the pipette tips ( 3 ) are multi-graded, the paragraph ( 17 ) forms a first stage and a second stage ( 28 ) near the bottom ( 9 ) of the block ( 2 ) is arranged. Pipetting device ( 1 ) according to claim 9, characterized in that the paragraph ( 17 ) within the block ( 2 ) is arranged at a level which is closer to the top ( 12 ) than at the bottom ( 9 ) of the block ( 2 ) is located. Pipetting device ( 1 ) according to claim 9 or 10, characterized in that each of the recordings ( 16 ) of the block ( 2 ) three cylindrical bores ( 29 . 29 ' . 29 '' ), wherein a first cylindrical bore ( 29 ) with a first diameter ( 30 ) from the top ( 12 ) of the block ( 2 ) to paragraph ( 17 ), a second cylindrical bore ( 29 ' ) with a second diameter ( 31 ) of paragraph ( 17 ) to the second stage ( 28 ) and a third cylindrical bore ( 29 '' ) with a third diameter ( 32 ) of the second stage ( 28 ) to the bottom ( 9 ) of the block ( 2 ) enough. Pipetting device ( 1 ) according to claim 11, characterized in that each insert ( 18 ) a first, second and third maximum diameter ( 39 . 40 . 41 ), which after insertion into the block ( 2 ) on the surface ( 12 ) of the block ( 2 ) and paragraph ( 17 ) and at the second stage ( 28 ) by a first, second and third free mass or gap ( 33 . 34 . 35 ) is smaller than a corresponding diameter ( 30 . 31 . 32 ) of the three cylindrical bores ( 29 . 29 ' . 29 '' ). Pipetting device ( 1 ) according to claim 9 or 10, characterized in that each of the recordings ( 16 ) of the block ( 2 ) two cylindrical bores ( 29 . 29 '' ), which from the top ( 12 ) of the block ( 2 ) to paragraph ( 17 ) and the second stage ( 28 ) to the bottom ( 9 ) of the block ( 2 ), and that each of the shots ( 16 ) of the block ( 2 ) a conical bore ( 38 ), which is covered by paragraph ( 17 ) to the second stage ( 28 ) enough. Pipetting device ( 1 ) according to claim 13, characterized in that each insert ( 18 ) a first, second and third maximum diameter ( 39 . 40 . 41 ), which after insertion into the block ( 2 ) on the surface ( 12 ) of the block ( 2 ) and paragraph ( 17 ) and at the second stage ( 28 ) by a first, second and third free mass or gap ( 33 . 34 . 35 ) is smaller than a corresponding diameter of the cylindrical bores ( 29 . 29 '' ) or the conical bore ( 38 ). Pipetting device ( 1 ) according to claim 11 or 13, characterized in that the lid ( 24 ) below the openings ( 25 ) cylindrical bores ( 36 ) in the same array as the openings ( 25 ) of the lid ( 24 ) are arranged, wherein the cylindrical bores ( 36 ) of the lid ( 24 ) have the same diameter as the first cylindrical bores ( 29 ) of the block ( 2 ), these cylindrical bores ( 36 ) of the lid ( 24 ) to each in a recording ( 16 ) included insert ( 18 ) a vertical free mass ( 37 ) provide. Pipetting device ( 1 ) according to one of the preceding claims, characterized in that the devices ( 20 ) to connect block ( 2 ) and multiple pipette head ( 6 ) Holding openings ( 20 ' ) with holding axes ( 21 ) for receiving at the multiple pipette head ( 6 ) fastened holding devices ( 22 ). Pipetting device ( 1 ) according to one of the preceding claims, characterized in that the pipetting device ( 1 ) one or more blind inserts ( 42 ) for insertion into selected recordings ( 16 ) of the block ( 2 ), each dummy insert ( 42 ) a cavity ( 8th ), an open cylindrical insertion opening ( 10 ) without inserted pipette tip ( 3 ) and a conical insertion opening ( 13 ) for sealingly inserting a pipette cone ( 5 ) of a multiple pipette head ( 6 ) and wherein each dummy insert ( 42 ) an edition ( 19 ), with which he in the block ( 2 ) used on the heel ( 17 ) of the corresponding recording ( 16 ) rests.

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