CA1049976A - Multiple sample pipetting apparatus - Google Patents

Multiple sample pipetting apparatus

Info

Publication number
CA1049976A
CA1049976A CA258,719A CA258719A CA1049976A CA 1049976 A CA1049976 A CA 1049976A CA 258719 A CA258719 A CA 258719A CA 1049976 A CA1049976 A CA 1049976A
Authority
CA
Canada
Prior art keywords
openings
plate
collector
tubes
plates
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.)
Expired
Application number
CA258,719A
Other languages
French (fr)
Inventor
William J. Byrd
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.)
Salk Institute for Biological Studies
Original Assignee
Salk Institute for Biological Studies
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 Salk Institute for Biological Studies filed Critical Salk Institute for Biological Studies
Priority to CA258,719A priority Critical patent/CA1049976A/en
Application granted granted Critical
Publication of CA1049976A publication Critical patent/CA1049976A/en
Expired 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
    • G01N35/1065Multiple transfer devices

Abstract

ABSTRACT
A Multiple Sample Pipetting Device is disclosed which is adapted to remove small predetermined volumes of liquid from a plurality of sample wells arranged in a compact rectilinear array, or conversely to transfer small predeter-mined volumes of liquid from one large reservoir container to a plurality of sample wells arranged in the same array. The apparatus has a plurality of small tubes extending downwardly with the upper end portion communicating with reservoirs that have a predetermined volume. A flexible diaphragm extends across all of the reservoirs, and the upper ends thereof are in communication with a common manifold chamber. The applica-tion of positive or negative pressure moves the diaphram downwardly and upwardly into contact with the lower and upper reservoir walls, respectively, and either extracts or expels liquid from the tubes. The manifold and tube holding portion of the apparatus is vertically movable so that the tubes can be lowered into the appropiate container to extract the pre-determined volume of liquid material.

Description

10~9976 This invention ~enerally relates to pipetting de-vices which are used in microbiological, immunological and medical laboratory research.
~ile pipetting devices and apparatus that are adapted to simultaneously withdraw a relatively large number Of samples ~rom individual wells of liquid samples are well known, many priority devices are adapted to simultaneously extract a relatively low number, i.e., a dozen or so samples in precise predetermined quantities within the ran~e of about 25 to about 50 microliters, other devices drop si%e for meter-ing which will extract a larger nu~ber of samples, i.e., 96 separate samples, typically have a volume capacity of only a few microliters, particularly when the size of the array or matrix of the total samples is relatively small. For those types of apparatus that have a flexible diaghragm that con-forms to the shape of a recess when vacuum pressure is applied for the purpose of suctioning a predetermined amount of liquid up into the suction tubes, the extremely confined and highly dense array may preclude the mere enlarging of the recesses ; 20 for the purpose of increasing the volume of the extracted liquid, because the enlargement may cause an overlap of the recesses with adjacent recesses.
Accordinaly, it is an object of the present inven-tion to provide an improved pipetting apparatus that is adapted to suction relatively large sample volumes considering the ; high density of the samples in the array.
According to the present invention, there is provided ` an apparatus for pipetting a plurality of predetermined quantities of a liquid, the apparatus having a collector plate provided with a plurality of openings, the lower portion of the ~ollector plate beina adapted to receive a plurality of ~_ ' ~ . ' - ' .

elongated hollow collector tubes in the openings, the op~ning communicatinq the lower surface with the upper surface, each of said openings in said upper surface having an enlarged generally smooth portion of a first predetermined volume. It is further provided a manifold plate having a recess in the lower surface thereof and an aperture communicating the recess with the opposite side thereof, the recess communicating fluid pressure from the aperture to the recess. An intermediate plate is located between the manifold plate and the collector plate and has openings generally coextensive with the openings in the collector plate, the openings communicating with the recess of the manifold plate, each of the openings having an en~arged generally smooth portion on the side adjacent the collector plate. Each of the enlarged portions has a second predetermined volume. A flexible impervious diaphragm is positioned between the intermediate plate and the collector plate and is adapted to be deflected upwardly or downwardly within each of the enlarged portions of the openings of the intermediate plate and collector plate, respectively, in response to selective application of fluid pressure thereto. A plurality of elongated hollow collector tubes are secured to the lower side of the collector plate within the openings. Means are provided for connecting the manifold plate aperture to sources of positive and negative fluid pressure for deflecting the flexible diaphragm in opposite directions, respectively. Frame means support the plates, the frame means being connected to at least one of the plates.
Other objects, features and advantages will become apparent upon reading the following detai~ed description, in conjunction with the attached drawings. in which:

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10~9976 E'I&UE~ 1 is a side elevation of apparatus embodyin~ the present invention;
FIGURE 2 is a top view of the apparatus shown in :

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FIGURE li FIGUE~ ~ is a cross sectional view, with portions removed, taken generally along the line 3-3 in FIGURE 2;
FIGURE 4 is a bottom plan view of the intermediate S plate of the apparatus shown in FIGURE 1 and particularly il-lustrating the array or ma~rix of openings therein; and, FIGU.RE 5 is an enlarged cross section of a portion of the collector plate illustrating the attachment of a typical co]lector tube to the collector plate.
Turning now to the drawings, and particularly FIGURE 1, there is shown apparatus 10, embodying the present invention which includes a support base 12, a vertical frame channel member 14 which is secured to the base 12 by an angle bracket 16 or the like. A plate assembly, indicated generally 15 at 1~, is attashed to a cross member 20 that is movable verti-cally in the channel 14. The cross member is adjustable by a ro `I tatabl~ knob 24 that is connected to a pinion gear (not shown~
that xides in a rack (not shown) within the channel 14. The rack and pinion geax arrangement enables the cross member ~0 and plate assembly 18 to he raised and lowered to the desired e]eva-tion as is nececsaxy to extract and deposit liquid samples. The ` plate assemhly 18 has a fle~ible tube 28 conr.ected thereto, with its opposite end connected to a valve means 30 which is sl~own to be a two-way solenoia valve that is actuated by an electrical switch 32. The solenoid valve has a common nozzle 34 to which the flexible tube 28 is connected and a~ternatively communicates the common nozzle 34 with nozzles 36 and 38 which are adapted to be connected to sources of vacuum and positive pressure, respectively. The plate assembly 18 has a plurality of col-lector tubes 40 extending downwardly from the underside thereof -for insertion into wells from which samples are to be taken.
The tub~s 40 are preferably about three inches along and fabri-:' ` .

1049~76 cated from stainless steel.
Turning to an important aspect of the present inven-tion and referring to FIGURE 3 which is a cross section taken generally along the line 3-3 in FIGURE 2, the plate assembly 18 comprises a manifold plate 42, a collector plate 44 into which the collector tubes 40 are secured and an intermediate plate 46 which is located between the manifold plate and the collector plate. A~flexible diaphragm 48 is positioned be-tween the intermediate and collector plates for reasons which will be hereinafter described. Referring also to FIGURE 5 the collector plate 44 has a plurality of openings 50 extend-ing therethrough, with the underside portions 52 of the open-ings being of increased diameter and terminating in an annular shoulder 54. The collector tubes 40 have an outside diameter that is slightly greater, i.e., a few thousandths of an inch than the inside diameter of the enlarged portion ~54 so that when they are inserted therein, they are compressed slightly to provide a snug, secure fit. Moreover, the inside diameter of the collector tubes 40 is preferably approximately equal to the diameter of the openings 50 adjacent thereto as shown in FIGURE 5. Near the upper side of the collector plate 44~ the openings 50 are enlarged into a generally smooth~ preferably hemispherical shaped portion 56~ as shown in FIGURES 4 and 5.
The size of the enlarged portion 56 is preferably predetermined so that when the diaphragm is displaced into contact with the surface of the hemispherical portion 56~ the volume displaced is of a precise predetermined amount.
The intermediateplate 46 also has a plurality of openings 58 that are coextensive with the openings 50 and which also have an enlarged portion 60 that is preferably simi-larly hemispherically shaped and of predetermined size. The ,.
manifold plate 42 has a large recessed portion 62 in the lower -3_ . . , ~
.

104997~
si.de ther~o whlch is coextellsive with all of the openings 58 in the intermediate ~l~te. ~n ~perture 64 communicates the por~ion 62 with a ccnn~ctor nozzl~ 66 (see FIGUR~ 1) to which the flexible conduit or t~ing 28 Ls attached. '~hu~, positive S or negative pressure that is present withi.n the tubiny 2~ is communicated to the recessed portion 62 through the aperture 64. Since the openings 58 in the inter~,edi.ate plate are in communication with the recessed portion 62 of the manifold ,plate, the ~osit~ve and negative pressure i.~ appl.ied to the lG flexible diaphragm 48 during operati.on. A seal 68 may be pro-vided around the periphery of the recessed portiGn between the intermediate and manifold plates to prevent leakage.
To transfer samples from receptacle to a plurali.ty of cul.ture wells, the receptacle having the culture material ~5 therein is placed below the plate assembly 18 on the base 12 and the switch 32 is placed in the positi.oIl whereby positi.ve pressure is applied thr.ough the noæ21e ~R and flexible cond 28 so that ~hepositive pressure deflects the diaphragm 48 downwardly into the hemispherical portions 56~ The knob 24 is then rotated so that the assembly 18 is lo~.~ered to immerse the ends of the tubes 40 into the liquid in the wells having the culture material therein. The switch 32 is then moved to the position whereby vacuum is communicated to the col~mon conduit 28 and the diaphragm 48 is deflected upwardly into contact wlth the walls of ~he enlarged portion 60 of t,h~ ~ntermediate plate.
By moving the impervious diaphragm 48 from the lower to the upper position, the liquid is suctioned upwardly into the col-, lector tubes 40. To transfer the liquid -from the collector ., ' tubes to another device~ the knob 24 is rotated to rai.se tlle assembly 18 so that another tray can be pl.aced beneath the col-lector tubes and the assen~ly can then b~ manipulated to the proper elevation whereupon the switch 32 can then be moved to -1(~4997~
apply positive pressure to thereby force the liquid from the tube~s to the desired locations.
In keeping with the present invention, while the manifold plate 42 is preferably securely attached to the cross support 20, the intermediate and col'ector plates are prefer-ably releasably secured to the manifold plate. To hold the plates together, four threaded screws 70 are positioned at the four corner portions of the manifold plate outside of the outer periphery of the recessed portion 62. The threaded screws 70 pass through larger diameter, non-interfering apertures 72 in the manifold and intermediate plates, respectively, and e..yage a threaded aperture in the collector plate. By tightenin~ the screws 70, the collector plate will be drawn upwardly so as to ~mpress the diaphragm 48 in sealing engagement and to tighten the manifold, intermediate, and collector plates together.
Conversely, by loosening the screws 70, the collector plate with the tubes sécured thereto can be remo~ed for cleaning ahd the intermediate plates 46 can also be removed for similax reasons.
In accordance with an important aspect of the present invention, the size of the enlarged port-ons 55 and 60 deter mine the volurne that is extracted by the pipetting apparatus ~Id, if the volurne traversed by the diaphrag~l in each of the hemispherical portions 56 and 60 of the plates is 50 microliters, for example, the application of positive and negative pressure in the manner as previously described will extract a s&mple volu~.e of about 100 microliters. In the event that some pre-cise quantity other than 100 microliters is desired to be ex-tracted, a separate intermediate plate 46 having nemispherical portions 60 which are of some other volurne than the 50 micro-; liters, i.e., about 25 microliters, for example, may be sub-stituted. Thus, by going through the operatin~ stéps previously ~. . : . .

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described, a total of 75 microliters may b~ extracted, since the mov~m~nt of the diaphragm from ~he io~er openinq 56 to the rest position snowrl in FIGUP~ 3 would e~fectively suction 50 microliters and the movement to the upper surf~ce of the hemis-S pherical portion 60 would suction an additional 25 microli-ters.
It should also be understood that 25 microliters may be ex-tracted by merely inserting the tubes in the well containing the cultures to be sampled withou~ applying positive pressure to deflect the membrane downwardly. In other words, the appli-cation of vacuum pressure would merely move the diaphra.3m 48 fromthe position shownin FIGURE 3 upwardly into contact with the hemispherical portions 60 which would effectively suction only 25 microliters.
As is sho-~n in FIGURE 4, the matrix or array of open-ings 58 in the intermediate plate 46 form a rectilinear matrixor array which comprises 12 rows, each of which have a total of 8 openings for a total of 96 places or locatio~Js. Sin~e --the cultural trays in which the sample cultures are developed are becoming increasingly standardized, it is preferred that the size o~ the matrix or array of collector tubes be compatible with the location of the individual culture wells in such trays.
Thus, it is preferred that the array of collector tubes 40 fit within the dimensions of about 2.5 to about 4 inches. Thus, the adjacent openings 58 will be spaced apart approximately 0.3~5 inches from center to cer.ter. The enlarged por~ions 56 of the collector plate as previously mentioned, are preferably hemispherical in shape and may have the dimensions. of about 0.125 inches in depth with a xadius of about 0.1875 inches.
~ith such dimensions, adjacent enlarged portions 56 do not merge with one another as is des.red.
It should also be understood that the sources of vacuum and positive pressure are typically present in most lab-, ' ' ` ~

10~9976oratories and the appar~tus embodying the present invention is compatible with ~ypical laboratory vacuum and positive pres-sures of about 15 pounds per square inch so that flexible tubing can be used for interconnecting the nozzles 36 and 38 S with the laboratory supplies.
The use of the snug fitting of the collector tubes 40 into the increased diame~er lower portion 52 of the openings 50 which terminates in the annular shelf ~2 has a quality ccn- :
trol advantage during fabricat;.on in that the tubes can be in-serted to a unifonm depth since the ends of the tubes cannot penetrate inwardly beyond the annular shelf 54.and therefore cannot penetrate into the hemispherical portion 56. If ~he ends of the tubes could enter the portion 56, they could cut : the diaphragm when it is defle.cted dowrlwardly upon application of positive pressure. Thus, the use of ~he annular shelf pre-; vents the ends of the inserted collector tubes from cutting the ~i.aphrasm and also provides a reliable and ~niform depth of insertion of the tubes within the collector pl2te during fabrication.
io Whlle various embodiments of the present invention ,`3 have been shown and described, various modifications, substi-tutions and alternatives will be suggested to those skilled .in . the art. Accordingly, the scope of the protection ~o be afforded this invention should not be limited by the particular embodiments shown and described, but should be determined in : tern~ of the definitions of the invention as set forth ir. the appended claims and equivalents thereof.
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Claims (16)

The embodiements of the invention in which an exclusive property or privilege is claimed are defined as follows:
1. Apparatus for pipetting a plurality of prede-termined quantities of a liquid, comprising: a collector plate having a plurality of openings, the lower portion of the col-lector plate being adapted to receive a plurality of elongated hollow collector tubes in said openings, said opening communi-cating the lower surface with the upper surface, each of said openings in said upper surface having an enlarged generally smooth portion of a first predetermined volume; a manifold plate having a recess in the lower surface thereof and an aper-ture communicating said recess with the opposite side thereof, said recess communicating fluid pressure from said aperture to said recess; an intermediate plate located between said mani-fold plate and said collector plate and having openings gener-ally coextensive with the openings in said collector plate, said openings communicating with said recess of said manifold plate, each of the openings having an enlarged generally smooth portion on the side adjacent said collector plate, each of said enlarged portions having a second predetermined volume;
a flexible impervious diaphragm positioned between said inter-mediateeplate and said collector plate and adapted to be de-flected upwardly or downwardly within each of said enlarged portions of said openings of said intermediate plate and col-lector plate, respectively, in response to selective applica-tion of fluid pressure thereto; a plurality of elongated hollow collector tubes secured to the lower side of said collector plate within said openings; means for connecting said manifold plate aperture to sources of positive and negative fluid pres-sure for deflecting said flexible diaphragm in opposite direc-tions, respectively; and, frame means for supporting said plates, said frame means being connected to at least one of said plates.
2. Apparatus as defined in Claim 1 wherein said second predetermined volume is approximately 50 microliters.
3. Apparatus as defined in Claim 1 wherein the lower portion of said openings in said collector plate have an increased diameter terminating in an annular shelf, the ends of said collector tubes abutting said annular shelf.
4. Apparatus as defined in Claim 3 wherein the in-side diameter of said tubes is approximately equal to the out-side diameter of said opening adjacent said annular shelf.
5. Apparatus as defined in Claim 1 wherein said en-larged openings are generally hemispherical in form.
6. Apparatus as defined in Claim 1 wherein an al-ternate intermediate plate having said enlarged portions with a third predetermined volume can be substituted for the initial intermediate plate having said second predetermined volume.
7. Apparatus as defined in Claim 6 wherein said third predetermined volume is approximately 25 micrometers.
8. Apparatus as defined in Claim 1 wherein said frame means includes a vertical member and a vertically adjust-able cross member operably associated therewith, said manifold plate being attached to said cross member so that all of said plates are vertically adjustable.
9. Apparatus as defined in Claim 8 including re-leasable attachment means for releasably attaching said mani-fold, intermediate and collector plates together.
10. Apparatus as defined in Claim 9 wherein said attachment means comprises one or more threaded screws engaging a threaded aperture in one of said plates to thereby hold said plates together.
11. Apparatus as defined in Claim 1 wherein said means for connecting said sources of positive and negative pres-sure comprises d flexible conduit having one end attached to said manifold aperture, the opposite end thereof being con-nected to valve means for communicating field flexible conduit to the source of positive pressure when in a first position and to the source of vacuum pressure when in a second position.
12. Apparatus as defined in Claim 11 wherein said valve means comprises an electrically actuated solenoid valve.
13. Apparatus as defined in Claim 8 wherein said vertical member and vertically adjustable cross member are in-terconnected by a rack and pinion gear arrangement having a ro-tatable knob for adjusting the elevation of said plates and collector tubes.
14. Apparatus as defined in Claim 1 wherein said openings in said collector plate are arranged in a rectilinear array.
15. Apparatus as defined in Claim 14 wherein said rectilinear array comprises 8 parallel rows, each row having 12 openings.
16. Apparatus as defined in Claim 1 wherein said dia-phragm comprises rubber.
CA258,719A 1976-08-09 1976-08-09 Multiple sample pipetting apparatus Expired CA1049976A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA258,719A CA1049976A (en) 1976-08-09 1976-08-09 Multiple sample pipetting apparatus

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CA258,719A CA1049976A (en) 1976-08-09 1976-08-09 Multiple sample pipetting apparatus

Publications (1)

Publication Number Publication Date
CA1049976A true CA1049976A (en) 1979-03-06

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
CA258,719A Expired CA1049976A (en) 1976-08-09 1976-08-09 Multiple sample pipetting apparatus

Country Status (1)

Country Link
CA (1) CA1049976A (en)

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