CA2132270A1 - Automatic pipetting apparatus having a cleaning device - Google Patents

Automatic pipetting apparatus having a cleaning device

Info

Publication number
CA2132270A1
CA2132270A1 CA002132270A CA2132270A CA2132270A1 CA 2132270 A1 CA2132270 A1 CA 2132270A1 CA 002132270 A CA002132270 A CA 002132270A CA 2132270 A CA2132270 A CA 2132270A CA 2132270 A1 CA2132270 A1 CA 2132270A1
Authority
CA
Canada
Prior art keywords
valve
tube
pipetting
connection
plunger pump
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
CA002132270A
Other languages
French (fr)
Inventor
Erich Lerch
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
F Hoffmann La Roche AG
Original Assignee
F Hoffmann La Roche AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG
Publication of CA2132270A1 publication Critical patent/CA2132270A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1004Cleaning sample transfer devices
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1004Cleaning sample transfer devices
    • G01N2035/1006Rinsing only the inside of the tip
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • Y10T436/113332Automated chemical analysis with conveyance of sample along a test line in a container or rack
    • Y10T436/114998Automated chemical analysis with conveyance of sample along a test line in a container or rack with treatment or replacement of aspirator element [e.g., cleaning, etc.]
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/25Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2575Volumetric liquid transfer

Abstract

Abstract An automatic pipetting device in which only one pipetting needle is available with an appropriate metering or transport means for the pipetting needle, the pipetting needle being connected to a metering syringe by a first tube and a first T-connection.

In order to allow rapid and thorough cleaning of the interior of the pipetting needle with minimum complexity, the pipetting device has one arm of the first T-connection (13) is connected to a cleaning means comprising the following components:

a) a plunger pump (24) connected by a second T-connection (23), a second tube (22) and 3 first valve (21) to one arm of the first T-connection (13), b) a suction tube (32), which is immersed in a cleaning liquid contained in a container (33) and which is connected to one arm of the second T-connection (23) by a second valve (31), and c) a control means (41) for controlling the first valve (21), the second valve (31 ) and the plunger pump (24).

(Fig. 1)

Description

2:~32270 , RAN 4090/24Ç

The invention r~lates to an automatic pipetting device in which only one pipetting needle is available with an appropriate metering or transport means for the pipet~ing needle, the pipetting needle being connected to a metering syringe by a first tube and a firs~ T-connection.
In the area of automatic analysers, for example those used for performing chemical analyses clinicaily, automatic pipe~ting devices of the above kind are known which usually fQrm part of such an analyser and whieh serve for metering and transferring 15 liquid samples or specimens and reagents between various containers, e.g. from a reagen~ container or sarnple or specimen container into a measuring dish where a mixture of sample or specirnen and reagent is formed and is analysed in the analyser.
I<nown pipetting devices of this kind comprise a transport means 20 which moves the pipetting needle into a number o~ pipetting positions and, between the pipe~ting operations, into a cleaning position, where the pipetting needle is cleaned with a suitable liquid, so that each pipetting operation may be earriPd out with a clean pipet~ing needle free from residues of any previous 2s pipetting operation.

in the case of larger analysers, ~wo independent pipe~ting devices, for example, are provided each with its own appropriate me~ering and transpor~ means for the pipet~ing need3es. This 30 enables either pipe~tin~needle to be used alternately while the other pipe~ting needle is being cleaned. Since the cleaning of one of the pipetting needles and the use of the other pipetting needle for performing a pipetting operation ~ake place simuitaneously, ~he duration of the wofking cycle of the pipetting device is no~
35 leng~hened by ~he interval for cleaning ~he pipetting needle, i.e.
the duration of the in~erval required for cleaning the pipe~ting needle does not affect the duration of the working cycle of the pipettin~ deviees of the analyser and therefore has no effee~ on ~he duration Qf the analyser working cycle. The sample or Ve:/So 29.8.94 . ~., , , ~. . . . . . . . .

- 2 ~13227~
..-specimen throughput, i.e. the number of samples or specimens which can be examined with the analyser per unit of time, is thPrefore independent of the duration of the interval required for cleaning the pipetting needle.

In the case of smaller analysers, with ~he aim of minimunn apparatus complexity, there is usually just one pipetting device available, i.e. just one pipet~ing needle with its metering and transport means. One consequence of this simplification of the 0 analyser is that the in~erval required for cleaning ~he pipetting needle must be integrated into the analyser working cycle. The latter thus becomes longer and sample or specirnen throughput becomes reduced.

Accordingiy, ~he object of the inven~ion is to provide a pipetting device of the type referred to hereinbefore, which requires the shortest possible interval for cle~ning ~he pipetting needle, but which guarantees thorough cleaning ~hereof.

2~ According to the invention, this objPct is achieved with a pipetting device of the type referred ~o hereinbefore, in which one arm of the first T-connection is connected to a cleaning means comprlsing the following components: -2s a) a plunger pump çonnec~ed by a second T-connection, a second tube and a first valvP to one arm of the first T-connection, b) a suction tube, which is immersed in a cleaning liquid 30 con~ained in a container and which is connected ~o one arm of the second T-connection by a second valve, and c) a control means for con~rolling the firs~ valve, the second valve and the plunger pump.
3s In a preferred embodiment of ~he pipetting device according to the invention one arm of the first T-eonnection is eonnected to a cleaning means comprising the following components:

. . . . ... . .
3 213227~
.
a~ a plunger pump connected by a second T-connection, a second tube and a valve to one arm of the first T-connection, b) a suction tube, which is immersed in a cleaning liquid contained in a container and which is connected to one arm of the second T-connection by a non-return valve, and c) a control means for controlling the valve and the 0 plunger pump.

The main advantage of the pipe~ting device according to the invention over prior art pipet~ing devices is that thorough cieaning of ~he pipetting needle is achieved in a relatively short 15 time and wi~h minimum expense ir: terms of materials.

Exemplified embodirnents of the invention will ~e described hereinafter with reference to the accompanying drawings in which:
Fig. 1 is a diagram showing a pipet~ing device according to the invention.

Fig. 2 is a preferred variant of ~he pipe~ting device according to 2s Fig. 1.

As shown in Fig. 1, a pipe~tiny device according to the invention comprises only one metal pipetting needle 11 connectled to a high-precision me~ering syringe 14 by a firs~ tube 12, e.g. a 30 Teflorl tube, and a first T-connection 13, the first tube 12 being ~ -connected ~o one arm 15 uf the T-connection 13 and the outlet of :he metering syrlnge 14 being connec~ed by a tube 19 to one arm 17 of ~he T-connec~ion 13.

The metering syringe 14 has a me~al cylinder and a piastic plunger with a rubber seal, its spindle being driven by a stepping motor.

,. ~ ~ ,. . .
.~ .

213227~
,..
In operation, the metering syringe 14 and a part of the tube 12 connected thereto contain a volume of water as a pressure transmission medium. The volume of a liquid for pipPtting with the pipetting needle, e.g. a reagent from a reagent container or 5 sample or specimen from a sample container, is received in the interior of the pipetting needle 11 and, if necessary, partly also in an adjoining part of ~he tube 12. The liquid for pipetting is separated from the water in the tube 12 by an air bubble.

The pipetting device according to the invention comprises a transport means for the pipetting needle. The transport rneans comprises a bar 52, movable in the direction of the arrow by a drive (not shown), and a transport carriage 51 for the pipetting needle 11. Carriage 51 is movable along the bar 52 in the 15 direction of the arrow by means o~ a drive (not shown). The carriage 51 contains a drive (not shown) by means of which the pipetting neeclle 11 is movable in the direction of the arrow. The above-described transport rneans enables the pipetting needle to be moved in three direc~ions at right angles to one another so 20 that it can be brought into a number of pipe~ting positions and also in~o a cleanin3 position.

In the cleaning position, cleaning liquid is pumped through the pipetting needle 11. The cleaning liquid which thereby 25 emerges from the pipetting needle is received by a container 38.
During the cleaning operation the pipe~ting needle 11 has the position shown in broken lines in Fig. 1 with respect to the container 380 One arm 16 of the first T-connection 13 is connected to a cleaning device cornprising the following components:

a~ a plunger pump 24 connected to the arm 16 of the first T-connection 13 by a secon~ T-connection 23, a second tube , 3s 22, a first valve 21 and a tube 18, the second tube 22 being - connected to one arm 15 of the T-connection 23 and the outle~ of the plunger pump 24 being connected to one arm 27 of the T-connec~ion 23 by a tube 29, 213227~ ~;
-.. ` ` ~ - ~ -b) a suction tube 32 immersed in a cleaning liquid 34 contained in a container 33 and connected via a second valve 31 and a tube 28 to one arm 26 of the second T-connection 23, and S : ~
c) a control device 41 for controlling the first valve 21, ~ :
the second valve 31 and the plunger pump 24. b In a preferred embodiment, the control device is arranged 0 such ~hat it can control the first valve 21, the second valve 31 .
and the piunger pump 24 in such a manner that the following cycle ~akes place to perform a cleaning operation on the pipettlng needle l 1~

During a first interval, in which the second valve 31 is kept open and the first valve 21 is kept closed, cleaning liquid is sucked from the container 33 by the plunger pump 24. The first interval lasts about 7.8 seconds.
: , , During a subsequent second interval, in which the second~ -:
valve 31 and the first valve 21 are kept closed, ~he pressure in ~: the tubes 22, 28, 29 is raised by the plunger pump 24. The second interval lasts abolu~ 0.2 seconds.

2s During a su~sequent third :in~erval, in which the first valve ;~ :-~; 21 is kept open~and ~he second vaive 31 kept closed, the pressure - -in the tubes 22, 28, 23 is kept substantially constan~ by the :~ plunger pump 24, par~ of the cleaning liquid contained in the second tube 22 flowing out through the firs~ tube 12 and the ;: -30 pipet~ing needle 11. The third interval lasts about ~ seconds.
The plunger pump 24 has a metal cylinder and a plastic plunger with a rubber seal, i~s spindle being driven by a stepping ;:
motor.
3s - ::
The plunger pump 24 serves to form a pressure in ths tubes 22, 28, 28 during the above-mentioned second interval, the pressure being such that in the above-mentioned ~hird in~erval ~.

213227~

the flow of cleaning liquid through the pipetting needle is a turbulent flow. This type of flow permits thorough cleaning of the interior of the pipetting needle in a very short time.

s The flow of cleaning liquid through the first tube 12 should preferably also be turbulent, but within the scope of the invention it is sufficient for it to be a defined flow, which may be turbulen~ or laminar.

In order to achieve these flow conditions, all the participating components must have suitable dimensions. The dimensions of the pipetting needle 11 and of the tube 12 connected thereto will depend on the required accuracy of the volumes for pipetting within the range of volumes of ~he liquids 15 for pipetting. This range may, for example, comprise small volumes, e.g. between 2 and 50 rnicrolitres for specimens, and larger volumes of up to about 200 microlitres for reagents. i~
has been found that for this volume range the pipetting needle should have an inside diameter of about 0.4 mm and the tube 12 20 should have an inside diameter of about 0.8 mm in order to achieve the required accuracy of the pipetted volumes. The rninimum length of the tube 12 is deterrnined substan~ially by the maximum volume for pipetting. In the present exemplified embodiment the pipetting nesdle 11 has an inside diameter of 0.4 mm and a length of 115 mm; the tube 12 has an inside diameter vf ~ -0.8 mm and a iength of 500 mm.

The other tubes in Fig.1 have inside diameters o~ 1.6 and 3 mm.

Experiments have shown that with the above dimensions of the pipe~ting needle 11 and of the various tllbes a flow of 2.5 millilitres of cleaning liquid within 2 seconds through the pipetting needle 11 is required to give a good cleaning effect of 35 the interior of the pipetting needle 11 and of the tube 12.

In the cleaning operation the hydraulic resistance of the pipetting needle 1 1 and of the tube 12 produces practically ~he 21~227~

entire pressure loss while the pressure loss caused by the other components is practically negligible.

In order to produce the required turbulent flow in the s pipetting needle 11 during the cleaning operation, it is necessary, under the above conditions, to generate a pressure about 6 bar in ~he tubes 22, 28, 29 in the above-mentioned second and third intervals by means of the plunger pump 24. In a preferred embodiment, each of the tubes 22, 28, 29 consists of a rigid 0 material, i.e. a material which is practically non-deformable by the pressure of 6 bars, e.g. polyethylene. The choice of such a material fGr ~he tubes 22, 28, 29 ensures ~hat ~he required pressure of about 6 bar and hence the required action of the cleaning means is main~ained for a relatively long period.
Before the beginning of each cleaning operation all the tubes in Fig. 1 and also the pipetting needle 11 are vented by filling with cleaning liquid from the container 33. The valves 21, 31 and the plunger pump 24 are suitably controlled by the control means 41 for this ven~ing operation as well. Only after the ven~ing operation do the above ~hree intervals in the eleaning opera~ion take place.
After each cleaning operation! the valve 2î is closed in a 25 fourth interval and ~he vaive 31 opened in order to allow the pressure in the ~ube system 279 28, 29 to drop to atmospheric pressure and take in fresh cleaning liquid 34. In this way the apparatus is prepared for ~he next eleaning cycle.

Fig. 2 shows a preferred variant of the pipetting device according to Fig. 1. In the variant according ~o Fig. 2, a non-return valve 61 is used instead of the valve 31 in Fig. 1. The non-return valve 61 requires no control by the control means 41. If the plunger pump 24 produces a vacuum in the li~e 2~, the non-3s return valve 61 is thus opened or kept open. When the plunger pump 24 produces a positive pressure in the line 28, ~he non-re~urn valve 61 is thus closed or kept closed.

, ~. . , . ,, . . , .. ~ , . . . .

8 ~1 32~70 ~, In the variant according to Fig. 2, the control means 41 is so arranged as to control the valve 21 and ~he plunger pump 24 in such manner that the following cycle takes place for performing a cleaning operation on the pipetting needle:

During a first interval, in which ~he valve 21 is kept closed and cleaning liquid is drawn in from the container 33 by the plunger pump 24, the non-return valve 61 is kept open by the negative pressure produced as a resul~, during a subsequent second in~erval, in which the valve 21 is kept closed and the pressure in the tubes 22, 28, 29 is raised by the plunger pump 24, the non-return valve 61 is kept closed by the pusi~ive pressure produced as a result, during a subsequen~ third interval, in which the valve 21 is kep~ open and the non-return valve 61 remains closed by the positive pressure, the pressure in the tubes 22, 28, 29 is kept approximately constant by the plunger pump 24, part of the ~o cleaning liquid contained in the second tube 22 flowing out through the first tube 12 and the pipetting needle 11.

The cons~ruction and operation of the embodimen~ according ~: -to Fig. 2 is othenNise identical to or similar to ~hat described : -2s above for ~he embodimen~ according to Fig. 1. :
~ .
In both the embodiments described above, ~he control means 41 suitably controls both the stepping motor of the plungPr pump 24 and the stepping motor of the rne~ering syringe 14. For the 30 above-described cleaning operation, the control of lthe plunger pump 24 by the control means 41 is important. The control of the stepping motor for the metering syringe 14 by the con~rol means 41, on the other hand, is important for the metering operation which takes place outside the time of the cleaning operaticn.
3s ,~ . . ..

Claims (8)

1. An automatic pipetting device in which only one pipetting needle is available with an appropriate metering or transport means for the pipetting needle, the pipetting needle being connected to a metering syringe by a first tube and a first T-connection, one arm of the first T-connection is connected to a cleaning means comprising the following components:

a) a plunger pump connected by a second T-connection, a second tube and a first valve to one arm of the first T-connection, b) a suction tube which is immersed in a cleaning liquid contained in a container and which is connected to one arm of the second T-connection by a second valve, and c) a control means for controlling the first valve, the second valve and the plunger pump.
2. A pipetting device according to claim 1, wherein the control means is arranged such that the first valve, the second valve and the plunger pump are controllable in such a manner that the following cycle takes place to perform a cleaning operation on the pipetting needle:

during a first interval, in which the second valve is kept open and the first valve kept closed, cleaning liquid is drawn in from the container by the plunger pump, during a subsequent second interval, in which the second valve and the first valve are kept closed, the pressure in the second tube is raised by means of the plunger pump, and during a subsequent third interval, in which the first valve is kept open and the second valve kept closed, the pressure in the second tube is kept approximately constant by means of the plunger pump, some of the cleaning liquid contained in the second tube flowing out through the first tube and the pipetting needle.
3. A pipetting device according to claim l, wherein the second tube consists of a rigid material.
4. A pipetting device according to claim 1, wherein the second tube consists of polyethylene.
5. An automatic pipetting device in which only one pipetting needle is available with an appropriate metering or transport means for the pipetting needle, the pipetting needle being connected to a metering syringe by a first tube and a first T-connection, in which one arm of the first T-connection is connected to a cleaning means comprising the following components:

a) a plunger pump connected by a second T-connection, a second tube and a valve to one arm of the first T-connection, b) a suction tube, which is immersed in a cleaning liquid contained in a container and which is connected to one arm of the second T-connection by a non-return valve, and c) a control means for controlling the valve and the plunger pump.
6. A pipetting device according to claim 5, wherein the control means is arranged such that the first valve and the plunger pump are controllable tin such a manner that the following cycle takes place to perform a cleaning operation on the pipetting needle:
during a first interval, in which the valve is kept closed and cleaning liquid is drawn in from the container by the plunger pump, the non-return valve is kept open by a negative pressure produced thereby, during a subsequent second interval, in which the valve is kept closed and the pressure in the second tube is raised by means of the plunger pump, the non-return valve is kept closed by a positive pressure produced thereby, during a subsequent third interval, in which the valve is kept open and the non-return valve kept closed by positive pressure, the pressure in the second tube is kept approximately constant by means of the plunger, some of the cleaning liquid contained in the second tube flowing out through the first tube and the pipetting needle.
7. A pipetting device according to claim 5, wherein the second tube consists of a rigid material.
8. A pipetting device according to claim 5, wherein the second tube consists of polyethylene.
CA002132270A 1993-10-28 1994-09-16 Automatic pipetting apparatus having a cleaning device Abandoned CA2132270A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH325393 1993-10-28
CH3253/93 1993-10-28

Publications (1)

Publication Number Publication Date
CA2132270A1 true CA2132270A1 (en) 1995-04-29

Family

ID=4251973

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002132270A Abandoned CA2132270A1 (en) 1993-10-28 1994-09-16 Automatic pipetting apparatus having a cleaning device

Country Status (4)

Country Link
US (1) US5474744A (en)
EP (1) EP0651255A1 (en)
JP (1) JPH07185360A (en)
CA (1) CA2132270A1 (en)

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