AU761965B2 - Reaction receptacle apparatus - Google Patents

Description

AUSTRALIA

Patents Act COMPLETE SPECIFICATION

(ORIGINAL)

Class Int. Class Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority Related Art: Name of Applicant: S Gen-Probe Incorporated Actual Inventor(s): Glenn A Horner, Shirley J Johnson, Robert E Schneider, Robert J Smith, Gus Tseo *.:..'Address for Service: 000 PHILLIPS ORMONDE FITZPATRICK Patent and Trade Mark Attorneys 367 Collins Street Melbourne 3000 AUSTRALIA "Invention Title:

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REACTION RECEPTACLE APPARATUS :OurRef: 653373 POF Code: 374700/374700 .The following statement is a full description of this invention, including the best method of performing it known to applicant(s): -1- REACTION RECEPTACLE APPARATUS This application is a divisional application of Australian Patent Application 72641/98 (735267), the entire contents of which are herein incorporated by reference.

FIELD OF THE INVENTION The present invention relates to reaction receptacles useful for containing chemical or biological substances.

BACKGROUND OF THE INVENTION Reaction receptacles or test tubes are commonly used in the chemical and biological arts to perform a variety of types of assays in a contained space.

Assays that commonly have one or more steps performed in reaction receptacles include chemical reactions, immunoassays, and nucleic acid-based assays. Examples of such reactions and assays are thoroughly described in the available literature and are well known to those skilled in the art. While reaction receptacles are generally manufactured and sold as individual units or test tubes, it is common for practitioners to use holding racks to conveniently and S 20 collectively organize a group of reaction receptacles for performing multiple assays simultaneously or sequentially. In some instances, multiple reaction receptacles are assembled as a unitary piece.

*i 735267 cdairs.doc With most assays, a substance transfer device is used to dispense solutions into or remove solutions from reaction receptacles. The most familiar substance transfer devices are pipettes and aspirators including one or more tubular elements through which fluids are dispensed or withdrawn. When substance transfer devices are used in conducting a group of independent assays at about the same time or in close proximity to one another, there is always the concern that a substance transfer device will inadvertently serve as a vehicle in transferring substances or contaminants between reaction receptacles. An additional concern is that the practitioner will improperly add substances into or remove substances from a reaction receptacle.

S15 To minimize the risk of cross-contamination and opipetting and aspirating errors, practitioners must "carefully monitor substance transfers and exercise Qo nearly flawless precision when pipetting substances e .into or aspirating substances from reaction receptacles. Avoiding cross-contamination and pipetting and aspirating mistakes is particularly important when the assay is diagnostic in nature or is designed to provide information concerning the progress of a patient's disease over time or the success of a treatment regimen.

One way to limit opportunities for crosscontamination is to reduce the amount of surface area on the substance transfer device that carl come into contact with the contents of a reaction receptacle.

This objective can be achieved by using a contactlimiting element, such as a pipette tip, which essentially serves as a barrier between the outer surface of the pipette and the contents of a reaction receptacle. And by selecting a pipette tip of sufficient length and volume, contact between the pipette and contents of a reaction receptacle can be substantially eliminated. This is because substances from the reaction receptacle will be drawn into a portion of the pipette tip which falls below the bottom surface of the pipette. Of course, in most instances, it will also be important to have a single pipette tip dedicated to each reaction receptacle.

15 Where a number of pipette tips are used to perform 0@e@ Soomultiple assays simultaneously or sequentially, e° practitioners typically need to position a supply of pipette tips at a location that can be conveniently e" accessed by at least one pipette. Providing a sufficient quantity of pipette tips becomes more complicated when the substance transfer device "':functions robotically in an automated (or partially ee e automated) assay instrument. In an automated format, a large reserve of pipette tips may need to be placed in 00 the instrument at a site that is accessible by the pipette, but which limits the total amount of space 0@0 required. Accordingly, there is a need for pipette tips that are readily accessible by a robotic pipette tips that are readily accessible by a robotic pipette without requiring the pipette to engage in complicated movements or to travel over substantial distances.

Another problem presented by conventional reaction receptacles is that they come packaged as individual test tubes that are not amenable to manipulation by an automated assay instrument. Individual reaction receptacles hinder throughput efficiency since the practitioner and instrument must each handle the reaction receptacles separately. And because conventional reaction receptacles are not provided with any structure that permits them to be manipulated by an automated instrument, reaction receptacles are generally stationed at one situs within the instrument and are not afforded any automated mobility. This lack of movement imposes certain architectural limitations and assay inefficiencies since the instrument must be designed around the positioning of the reaction receptacles. Accordingly, there is a need for a reaction receptacle apparatus which can be manipulated by an automated assay instrument, where the apparatus may include one reaction receptacle or plurality of reaction receptacles coupled together as a single operative unit.

The discussion of the background to the invention herein is included to explain the context of the invention. This is not to be taken as an admission that any of the material referred to was published, known or part of the common OO general knowledge in Australia as at the priority date of any of the claims.

g Throughout the description and claims of the specification the word "comprise" and variations of the word, such as "comprising" and "comprises", is not intended to exclude other additives, components, integers or steps.

25 SUMMARY OF THE INVENTION oo..oi It would be desirable to provide a reaction receptacle apparatus that

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meets one or more of the needs set forth above. Thus, a reaction receptacle apparatus according to the present invention can be used to perform chemical or biological assays and comprises at least one reaction receptacle for containing substances used in performing such assays.

o 735267- claims.doc In one aspect the present invention provides a receptacle apparatus for use in performing a chemical or biological assay, the apparatus comprising: a plurality of aligned receptacles, each receptacle comprising a hollow body, an open top end and a closed bottom end, wherein the receptacles are capable of interacting with a substance transfer device constructed and arranged to dispense fluid into or withdraw fluid from one or more of the receptacles; one or more contact-limiting element holding structures, each contactlimiting element holding structure being adjacent the open top end of at least one of the receptacles and comprising a body having an orifice therein for removably receiving a contact-limiting element; and a connecting rib structure fixedly connecting the receptacles to one another, wherein the receptacles, the contact-limiting element holding structures and the connecting rib structure form an integral piece.

So that the substance transfer device can safely and efficiently dispense substances into or withdraw substances from the reaction receptacles, one embodiment of the present invention provides for one or more contact-limiting elements associated with the reaction receptacle apparatus. The contact- S-limiting elements of this embodiment are constructed and arranged to be 20 operatively engaged by the substance transfer device to limit potentially :o contaminating contact between at least a portion of the substance transfer device and a potentially contaminating substance that is dispensed into or o06 withdrawn from a reaction receptacle by the substance transfer device. One or more contact-limiting elements are associated with each of one or more of the reaction receptacles of the reaction receptacle apparatus.

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W:AskanikspedesfDIV 735267. claims.doc When the present invention includes contactlimiting elements, the reaction receptacle apparatus is outfitted with one or more contact-limiting element holding structures, each contact-limiting element holding structure being preferably associated with a different contact-limiting element. Each of the contact-limiting element holding structures is constructed and arranged to receive and removably hold the associated contact-limiting element in an operative orientation in proximity to the associated receptacle so as to be operatively engageable by the substance transfer device, and (ii) allow the associated contact-limiting element to be removed from the associated contact-limiting element holding structure when the associated contact-limiting element is operatively engaged by the substance transfer o- device.

Because this embodiment of the reaction receptacle 0000 apparatus is supplied with its own contact-limiting

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elements, an automated assay instrument can be constructed so that the substance transfer device avoids complex motions and conveniently engages the contact-limiting elements when the reaction receptacle apparatus is brought into an operative position within

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the instrument. An additional benefit of this embodiment is that the instrument does not have to be *0 configured to receive a store of contact-limiting So. elements, and practitioners are spared having to -6monitor the volume of contact-limiting elements in an instrument while assays are being run.

A further embodiment of the present invention is a reaction receptacle apparatus including receptacle apparatus manipulating structure to permit manipulation of the apparatus by an automated reaction receptacle manipulating device. According to this embodiment, the receptacle apparatus manipulating structure is constructed and arranged to be engaged by an automated reaction receptacle manipulating device, so that the reaction receptacle apparatus can be robotically manipulated within an automated instrument. The reaction receptacle apparatus of this embodiment includes at least one reaction receptacle and may 15 optionally include the contact-limiting elements and *Goo associated contact-limiting element holding structures described above.

°o Other features and characteristics of the present invention, as well as the methods of operation, functions of related elements of structure and the combination of parts, and economies of manufacture, will become more apparent upon consideration of the following description and the appended claims with reference to the accompanying drawings, all of which

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0* form a part of this specification, wherein like reference numerals designate corresponding parts in the S various figures.

S. S BRIEF DESCRIPTION OF THE DRAWINGS FIGURE 1 is a perspective view of a first embodiment of a reaction receptacle apparatus and contact-limiting element in the form of a tiplet embodying aspects of the present invention; FIGURE 2 is a side elevation of a contact-limiting tiplet; FIGURE 3 is a partial bottom view of the reaction receptacle apparatus of FIGURE 1 taken in the direction indicated by arrow "III" in FIGURE 1; FIGURE 4 is a side elevation of a first alternate embodiment of the reaction receptacle apparatus of the present invention; FIGURE 5 is a top view of the reaction receptacle apparatus of FIGURE 4; FIGURE 6 is a cross-section in the direction "VI- VI" of FIGURE 4; FIGURE 7 is a cross-section in the direction "VII- VII" in FIGURE 4; FIGURE 8 is a cross-section in the direction "VIII-VIII" in FIGURE 4; 0000 •FIGURE 9 is a perspective view of an exemplary reaction receptacle apparatus manipulating device for manipulating a reaction receptacle apparatus according 25 to the present invention; FIGURE 10 is a side elevation, partially in crosssection, of the manipulating device of FIGURE 9 with a reaction receptacle apparatus resident therein; FIGURE 11 is a side elevation, partially in crosssection, of an exemplary reaction receptacle apparatus processing device for processing a reaction receptacle apparatus according to the present invention; FIGURE 12 is a partial side view of a reaction receptacle apparatus according to the present invention and a skewed wobbler plate for imparting an oscillatory vibration to the apparatus; FIGURE 13 is a cross-section showing a reaction receptacle apparatus according to the present invention carried by a receptacle carrier structure within a receptacle apparatus processing device with a tubular element of the processing device engaging a contactlimiting tiplet disposed within a contact-limiting holding structure of the apparatus of the present 0000 6: invention; 06.0 FIGURE 14 is a cross-section showing the reaction *666 s receptacle apparatus disposed within the receptacle S-carrier structure with the tubular elements and the contact-limiting tiplet disposed on the end of the tubular element inserted into the apparatus; ~FIGURE 15 is a perspective view of a second 0 alternate embodiment of a reaction receptacle apparatus 0006 of the present invention; @006 6 00 S 25 FIGURE 16 is a perspective view of a third alternate embodiment of a reaction receptacle apparatus of the present invention; and 6 FIGURE 17 is a side elevation of an alternate embodiment of a contact-limiting tiplet engaged by a tubular element of a substance transfer device.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT As shown in FIGURES 1 and 3, a preferred embodiment of a reaction receptacle apparatus according to the present invention is designated generally by the reference character 160. As shown, the reaction receptacle apparatus 160 preferably comprises a plurality of individual receptacles 162. In the illustrated embodiment, the reaction receptacle apparatus 160 includes five individual receptacles 162, but a reaction receptacle according to the present

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invention may include any number of receptacles 162, as 4, 6 15 desired. Ten receptacles 162 are preferred and five a oe r 6 receptacles 162 are most preferred. Each individual receptacle 162 preferably has a construction similar to a e e that of a conventional test-tube, a cylindrical body with a circular open mouth 161 and a rounded closed bottom end 163. Each individual receptacle can,

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however, have other shapes, such as rectangular, octagonal, etc., and may have an upper end equipped S- with a closable lid structure or the like. Where the reaction receptacle includes a plurality of d 25 receptacles, the receptacles may have the same or Se6 different shapes and sizes. The receptacles 162 are 6* preferably oriented in an aligned arrangement comprising a single row of receptacles 162 and are connected to one another by a connecting rib structure 164 which defines a downwardly facing shoulder 165 extending longitudinally along either side of the reaction receptacle apparatus 160. The receptacles 162 may be oriented in a different nonlinear arrangement, or a single reaction receptacle apparatus may comprise more than one row of receptacles 162.

Reaction receptacle apparatus 160 is preferably a single, integral piece formed of injection molded polypropylene. The most preferred polypropylene is sold by Montell Polyolefins, of Wilmington, Delaware, product number PD701NW. The Montell material is used because it is readily moldable and is chemically compatible with the preferred biological assays •r •performed in the reaction receptacle apparatus.

Moreover, the Montell material experiences a limited number of static discharge events, which is important when the results of the assay performed in the reaction receptacle apparatus are determined by the detection of light emitted by the contents of the apparatus at the 0 -e conclusion of the assay. Static discharge events can interfere with accurate detection or quantification of S" 25 the light output.

An arcuate shield structure 185 provided at one end of the reaction receptacle apparatus 160 includes c* an upper portion 169 and a lower portion 173. A -11receptacle apparatus manipulating structure 166, adapted to be engaged by a reaction receptacle manipulating device, extends from the shield upper portion 169. Receptacle apparatus manipulating structure 166 comprises a laterally extending plate 168 extending from shield upper portion 169 with a transverse piece 167 on the opposite end of the plate 168. A gusset wall 183 extends downwardly from lateral plate 168 between shield lower portion 173 and transverse piece 167.

As shown in FIGURE 3, the shield lower portion 173 and transverse piece 167 have mutually facing convex Ssurfaces. The reaction receptacle apparatus 160 is preferably engaged by manipulating devices and other see. 15 components, as will be described below, by moving an e g engaging member of the manipulating device laterally Oe@@ the direction into a space 50 between the shield lower portion 173 and the transverse piece 167.

The convex surfaces of the shield lower portion 173 and 20 transverse piece 167 provide for wider points of entry "°"for an engaging member undergoing a lateral relative OeSS motion into the space 50. Vertically extending, raised arcuate ridges 171, 172 may be provided in the middle of the convex surfaces of the transverse piece 167 and 25 shield lower portion 173, respectively. The purpose of ridges 171, 172 will be described below.

A label-receiving structure 174 provided on an end of the reaction receptacle apparatus 160.opposite -12receptacle apparatus manipulating structure 166 preferably includes an upper portion 71 and a lower portion 75, which together present a flat labelreceiving surface 175. The label-receiving structure 174 further includes a vertical gusset wall 78 extending between upper portion 71 and the endmost receptacle 162 to provide a brace for the upper portion 71. As best shown in FIGURE 4, a gusset wall 80 of the label-receiving structure 174 is oriented vertically and extends diagonally from a location proximate rib structure 164 toward a lower end of lower portion 75 to provide a brace for lower portion 75. Labels, such as machine-scannable bar codes, can be applied to the surface 175 to provide identifying and instructional 5@50 15 information on the reaction receptacle apparatus 160.

Labels can be applied to surface 175 by any suitable 0@ means, such as, printing them onto surface 175 or adhering a label sheet, by means of an adhesive, to surface 175.

20 Substances can be dispensed into or removed from o the receptacles 162 through their open mouths 161 by means of a substance transfer device, such as a pipetting or aspirating apparatus (hereinafter referred to collectively as "pipetting apparatus" or "pipette") 25 The pipetting apparatus may include a slender tubular S"element (see, tubular element 220 in FIGURE 11) that is inserted into the receptacle 162 through the open mouth 161 and which may come into contact with the -13receptacle 162 itself, the substance contained in the receptacle 162, and/or the substance being dispensed into the receptacle. A pipetting apparatus may be used to dispense substances into and/or remove substances from multiple individual receptacles 162. Accordingly, to reduce the likelihood of cross-contamination between individual receptacles 162, it is desirable to limit the amount of the pipetting apparatus that comes into contact with the substance or walls of any receptacle 162. Therefore, a contact-limiting element, which may take the form of a protective disposable tip, or tiplet, covers the end of the tubular element of the pipetting apparatus. One contact-limiting element is used to cover the end of the tubular element while the 15 pipetting apparatus engages one individual receptacle o. to dispense substance into or withdraw substance from the receptacle. Before the pipetting apparatus moves 6go to the next receptacle, that contact-limiting element is discarded or stored for later use with that 20 receptacle, and a new contact-limiting element is 0 .6606. engaged by the tubular element.

As shown in FIGURE 2, a preferred embodiment of a contact-limiting element comprises a tiplet 170. In the preferred embodiment, tiplet 170 comprises a 25 tubular body 179 having a peripheral flange 177, preferably extending radially with respect to said tubular body 179, and a thickened wall portion 178, adjacent the peripheral flange 177, having a generally -14larger diameter than a remaining portion of the tubular body 179 of the tiplet 170. An axially extending inner bore 180 passes through the tiplet 170. Bore 180 includes an outwardly flared end 181, which facilitates insertion of a bottom free end of a tubular element of a pipetting apparatus into the bore 180 of tiplet 170.

The inner diameter of inner bore 180 provides an interference fit with the outer diameter of the tubular element to frictionally secure tiplet 170 onto the tubular element when the bottom end of the tubular element is forced into the inner bore 180.

In the illustrated embodiment, the tubular body 179 and inner bore 180 are generally cylindrical in 0* shape, consistent with the typically cylindrical shape 15 of the tubular element of a substance transfer device, such as a pipetting or aspirating device. The present invention is not limited, however, to contact-limiting elements having tubular bodies and inner bores that are cylindrical, as the tubular body and inner bore of the 20 contact-limiting element may have a shape that is other than cylindrical to conform to non-cylindrical tubular elements of substance transfer devices.

The.bottom end of the tiplet 170 preferably includes a beveled portion 182. When tiplet 170 is 25 used on the bottom of the tubular element of a pipetting apparatus used for aspirating substances from a receptacle 162, the beveled portion 182 will prevent a vacuum from forming between the end of the tiplet 170 and the bottom 163 of the receptacle 162.

An alternate embodiment of a contact-limiting element is a tiplet designated by reference number 470 in FIGURE 17. Tiplet 470 comprises a tubular body 479 having a peripheral flange 477, preferably extending radially with respect to said tubular body 479, and a thickened wall portion 478, adjacent the peripheral flange 477, of generally larger diameter than a remaining portion of the tubular body 479 of the tiplet 470. An axially extending inner bore 480 passes through the tiplet 470. Bore 480 includes a bevelled end 481, which facilitates insertion of an upper end 483 of the tubular body 479 into a bottom free end of a tubular element 420. The outer diameter of upper end 483 of the tubular body 479 provides an interference fit with the inner diameter of the tubular element 420 to frictionally secure tiplet 470 onto the tubular element 420 when the upper end 483 of the tubular body 479 is inserted into the bottom free end of the tubular *000 element 420.

Again, the tubular body 479 and inner bore 480 need not necessarily be generally cylindrical in shape, as illustrated in FIGURE 17, may have a shape that is 25 other than cylindrical to conform to non-cylindrical tubular elements of substance transfer devices.

00 The bottom end of the tiplet 470 preferably includes a beveled portion 482. When tiplet 470 is -16used on the bottom of the tubular element of a pipetting apparatus used for aspirating substances from a receptacle 162, the beveled portion 482 will prevent a vacuum from forming between the end of the tiplet 470 and the bottom 163 of the receptacle 162.

As shown in FIGURE 1, the reaction receptacle apparatus 160 preferably includes contact-limiting element holding structures in the form of tiplet holding structures 176 adjacent the open mouth 161 of each respective receptacle 162. Each tiplet holding structure 176 provides an elongated orifice 150, preferably generally cylindrical in shape, within which 0.0 is received a contact-limiting tiplet 170 (470). An annular end face 152 extends about the orifice 150, and S- 15 when the tiplet 170 (470) is inserted into a tiplet holding structure 176, the peripheral flange 177 (477) S. contacts the end face 152 of tiplet holding structure 176 to limit the depth to which the tiplet 170 (470) can be inserted into the orifice 150. The outside 20 diameter of the thickened wall portion 178 (478) is •0 slightly larger than inside diameter of the orifice 0. 150. Alternatively, and preferably, a plurality of small, raised ribs 154 (see FIGURE 3) extend longitudinally along the inner wall of the orifice 150 25 at different circumferentially-spaced positions. The crests of the raised ribs 154 define an inner diameter that is slightly smaller than the outer diameter of the thickened wall portion 178 (478). Accordingly, the -17tiplet holding structure 176 provides a sliding interference fit between the thickened wall portion 178 (478) and the inner diameter of the orifice 150 or between the thickened wall portion 178 (478) and the crests of the ribs 154. Thus, tiplet 170 (470) is held securely within the orifice 150 of the tiplet holding structure 176 so the tiplet 170 (470) is unlikely to dislodge from the tiplet holding structure 176, even if the reaction receptacle apparatus 160 is inverted. On the other hand, if the tiplet 170 (470) is frictionally engaged by the tubular element of a pipetting apparatus while the tiplet 170 (470) is held in the tiplet holding structure 176, the frictional hold between the tiplet 170 (470) and the tubular element is greater 15 than the frictional hold between the tiplet 170 (470) and the tiplet holding structure 176. Thus, the tiplet 170 (470) should remain secured on the end of the tubular element when the tubular element is withdrawn in an axial direction from the orifice 150 of the 20 tiplet holding structure 176.

Throughout the remainder of this specification, reference will be made only to tiplet 170 (the embodiment shown in FIGURE Those skilled in the art, however, will appreciate that the following 25 descriptions and illustrations can apply to tiplet 470 (the embodiment shown in FIGURE 17) as well.

An alternate tiplet holding structure 76 is shown in FIGURES 4 and 5. Reaction receptacle apparatus -18includes a tiplet holding structure 76 that is different from the tiplet holding structure 176 of reaction receptacle apparatus 160 of FIGURE 1. In all other respects, however, reaction receptacle apparatus 60 is identical to reaction receptacle apparatus 160.

Tiplet holding structure 76 includes a tiplet-receiving orifice 79 with an end face 77 surrounding orifice 79 and forming a partial annulus. A slot 78 extends longitudinally along a wall of the tiplet holding structure 76. Slot 78 allows the tiplet holding structure 76 to expand when a tiplet 170 is inserted into the tiplet holding structure 76, and the resiliency of the material of which the reaction Sreceptacle apparatus 60 is formed provides a frictional 15 fit between a tiplet 170 and the tiplet holding structure 76.

As shown in FIGURES 1, 4, and 5, connecting rib structure 164 extends along both sides of the reaction receptacle apparatus 160 and defines downwardly facing 20 shoulders 165 with outer edges 192 along each side of the reaction receptacle apparatus 160 The reaction receptacle apparatus 160 (60) is operatively supported within a diagnostic instrument or the like by means of the shoulders 165 resting on parallel, 25 horizontal flanges spaced apart from one another by a o distance slightly greater than the width of the individual receptacle 162, but less than the width of the rib structure 164 between edges 192. Such flanges -19-

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may be defined by a slot extending from an edge of a reaction receptacle apparatus supporting plate. In an automated instrument for processing the contents of a reaction receptacle apparatus, the reaction receptacle apparatus may be inserted into and removed from a supporting structure by a reaction receptacle apparatus manipulating device.

At an end of the rib structure 164 opposite the receptacle apparatus manipulating structure 166, two upwardly angled portions 82 provide upwardly angled shoulders 84 on both sides of the reaction receptacle apparatus 160 The upwardly angled shoulders 84 facilitate sliding of the reaction receptacle apparatus og160 (60) onto a supporting structure.

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An exemplary device 20 for manipulating a reaction *receptacle apparatus 160 (60) is shown in FIGURES 9 and 10. The device 20 includes a base structure 22 attached to a mounting bracket or mounting plate of an instrument which processes the contents of numerous 20 reaction receptacle apparatuses according to the *present invention and may perform one or more assays within each reaction receptacle apparatus 160. The manipulating device 20 moves the reaction receptacle apparatuses from one location to another within the 25 instrument.

The manipulating device 20 further includes a rotating transport carrier 28 which rotates about a shaft 25 by means of a stepper motor 24 which turns a pulley 29 attached to the shaft 25 via a drive belt 27.

The shaft 25 and pulley 29 may be covered by a pulley housing 26. The rotating transport carrier 28 includes a base plate 30 covered by a housing 32. The housing 32 includes an opening 36 at one end thereof, and the base plate 30 includes a slot 31 formed therein. A manipulating hook 34 is mounted for sliding translation in the slot 31 and is attached to a threaded drive screw 40 that is actuated by a stepper motor 38 to extend and retract the manipulating hook 34 within the slot 31.

To engage the receptacle apparatus manipulating structure 166 of the reaction receptacle apparatus 160, e the manipulating hook 34 is extended to a forward s 15 position projecting from the opening 36 as shown in a o. FIGURE 9. A lateral translation of the manipulating hook 34 is effected, such as by effecting a small rotation of the rotating transport carrier 28, to place the manipulating hook 34 in the space 50 between the 20 lower portion 173 of the arcuate shield structure 185 and the transverse piece 167 of the receptacle #6.0 apparatus manipulating structure 166. With the manipulating structure 166 engaged, the stepper motor 38 retracts the drive screw 40, pulling the 25 manipulating hook 34 and the reaction receptacle O apparatus 160 back into the rotating transport carrier 28. The downwardly facing shoulders 165 defined by the connecting rib structure 164 of the reaction receptacle -21apparatus 160 are supported by the base plate 30 along opposite edges 42 of the slot 31, thus supporting the reaction receptacle apparatus 160 in the rotating transport carrier 28. With the reaction receptacle apparatus 160 secured within the rotating transport carrier 28, the carrier 28 can be rotated by the stepper motor 24 to a different position at which the stepper motor 38 can extend the drive screw 40 and the manipulating hook 34 to push the reaction receptacle apparatus 160 out of the rotating transport carrier 28 and into a different location within the instrument.

An exemplary reaction receptacle processing device 200 is shown in FIGURE 11. Processing device 200 may 0000 ,represent one of many similar or related devices which .000, 15 together make up a reaction receptacle processing 0d00 *instrument.

0t00 The processing device 200 includes a housing 201 e e with an opening 202 formed therein. A reaction receptacle apparatus 160 can be inserted into the 20 processing device 200 through the opening 202 and *O O0 removed through the opening 202 by a manipulating see device such as the manipulating device 20 shown in o 5 o FIGURES 9 and 10 and described above. Inside the housing 201 the reaction receptacle apparatus is 25 supported by a receptacle carrier structure 206 having 0 a base plate 204 (see also FIGURES 13 and 14) with a receptacle receiving slot (not shown) formed therein so that the reaction receptacle apparatus 1-60 can be -22supported by means of portions of the plate 204 along opposite edges of the slot supporting the connecting rib structure 164 of the reaction receptacle apparatus 160.

Processing device 200 may be a mixing device for mixing the contents of the reaction receptacle apparatus 160; the processing device 200 may be a dispensing device for simultaneously dispensing substance into each of the individual receptacles 162 of the reaction receptacle apparatus 160; or the processing device 200 may be a device for simultaneously aspirating substance from each of the receptacles 162 of the reaction receptacle apparatus 00 160. Alternatively, the processing device 200 may perform any combination of two or more of the above 0000 functions.

As a mixing device, the receptacle carrier structure 206 may be coupled to an orbital mixing assembly comprising a stepper motor 208, a drive wheel 210 with an eccentric pin 212 extending therefrom, and 000 an idler wheel 216 having an eccentric pin 218 and being coupled to the drive wheel 210 by means of a belt 0 214. As the stepper motor 208 rotates the drive pulley 210 which in turn rotates the idler pulley 216, the .0 25 eccentric pins 212 and 218 engage the receptacle carrier structure 206 thus moving the receptacle carrier structure and the reaction receptacle apparatus 160 carried thereby in an orbital path of motion.

-23- Movement at a sufficiently high frequency can cause sufficient agitation of the reaction receptacle apparatus 160 to mix the contents thereof.

As shown in FIGURES 1, 4, and 5, lateral ribs 190 extend longitudinally along the outer walls of the receptacles 162 above the connecting rib structure 164 at diametrically opposed positions with respect to one another. The outer edges of the lateral ribs 190 are generally co-planar with the outer edges 192 of the connecting rib structure 164. The lateral ribs provide additional strength and rigidity to the open mouth 161 of the receptacle 162. In addition, the outer edges of the lateral ribs 190 can engage the sidewalls of a receptacle carrier structure 206, as shown in FIGURES 15 13 and 14, to limit the extent to which the reaction

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receptacle apparatus 160 will be allowed to tilt S laterally within the receptacle carrier structure 206.

00 Although it is generally preferred that lateral ribs 190 be provided on each of the receptacles 162, lateral 20 ribs 190, when included, can be provided on less than oo o• S"all of the receptacles 162 as well.

*000 GoesWhen presented in the receptacle carrier structure 206, the reaction receptacle apparatus 160 can be engaged by a dispensing and/or aspirating system S 25 comprising an array of tubular elements 220. The dispensing and/or aspirating system preferably includes five tubular elements 220 oriented so as to correspond to the orientations of the individual receptacles 162 -24of the reaction receptacle apparatus 160. The tubular elements 220 are coupled to means for providing vertical movement of the free ends of the tubular elements 220 with respect to the reaction receptacle apparatus 160 to move the ends of the tubular elements 220 into and out of the individual receptacles 162 to aspirate and/or dispense substances. In addition, tubular elements 220 are coupled to means, such as a fluid pump and fluid source or zi vacuum pump, for delivering fluid to each of the tubular elements 220 or providing a suction at each of the tubular elements 220.

As described above, however, before the tubular elements 220 are inserted into the reaction receptacles 15 162, it is preferred that a contact-limiting tiplet 170 a a be placed on the end of each tubular element 220.

60%69 Accordingly, the tubular elements 220 are first lowered to simultaneously engage all of the tiplets 170 carried in their respective tiplet holding structures 176. The array of tubular elements 220 can be coupled to means for providing lateral translation of the tubular sees elements 220 for moving the tubular elements 220 to a position above the tiplet holding structures 176.

Alternatively, the receptacle carrier structure 206 itself can be moved laterally to place the tiplet holding structures 176 below the respective tubular elements 220. Where the receptacle carrier structure 206 is coupled to an orbital mixing assembly as described above, the stepper motor 208 can move the assembly a limited number of steps, thus moving the receptacle carrier structure 206 and the reaction receptacle apparatus 160 a portion of one orbital path to place the tiplet holding structures 176 below the tubular elements 220 as shown in FIGURE 13.

As shown in FIGURES 1, 4, and 5, each of the respective tiplet holding structures 176 (76) is preferably disposed at a position between adjacent receptacles 162. Locating the tiplet holding structures 176 (76) between the adjacent receptacles 162 places the tubular elements 220 on the orbital paths of the contact-limiting element holding o structures 176 (76) as the reaction receptacle

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apparatus 160 is moved with respect to the pipettes 220. Thus, the orbital mixer assembly can be used to properly position the tiplet holding structures 176 000 (76) with respect to the tubular elements 220, as described above. In addition, placing the tiplet 20 holding structures 176 (76) between adjacent .receptacles 162 provides for a narrower profile of the reaction receptacle apparatus 160 (60) than if the o tiplet holding structures 176 (76) were located on the outer portion of the receptacles 162 nearest the edge •00 25 192 of the connecting rib structure 164.

The processing device 200 may also include an array of fixed nozzles 222 for dispensing substances into the receptacles 162 of the reaction receptacle -26- 00 0 0 0000 0 0 @000 0 0 apparatus 160 held in the receptacle carrier structure 206.

As shown in FIGURE 12, an alternate, oscillating mixing device 230 comprises a skewed wobbler plate 232 disposed on a shaft 234 driven by a motor (not shown) The reaction receptacle apparatus 160, carried by a carrier structure (not shown), is moved with respect to the oscillating mixing device 230 or the oscillating mixing 230 is moved with respect to the reaction receptacle apparatus 160 until the wobbler plate 232 is disposed in the space 50 between the lower portion 173 of the arcuate shield structure 185 and the transverse piece 167 of the receptacle apparatus manipulating structure 166. As the shaft 234 rotates, the position of the portion of the wobbler plate 232 engaged with the receptacle apparatus 160 varies in a linearly oscillating manner to impart a linear oscillating motion to the reaction receptacle apparatus 160.

The raised ridges 171, 172 provided in the middle of the convex surfaces of the transverse piece 167 and the lower portion 173, respectively, can minimize the surface contact between the wobbler plate 232 and the convex surfaces, thus limiting friction therebetween.

It has been determined, however, that raised ridges 171, 172 can interfere with the engagement of the manipulating hook 34 of a manipulating device 20 with -27the apparatus manipulating structure 166. Therefore, raised ridges 171, 172 are preferably omitted.

In the preferred embodiment of the reaction receptacle apparatus of the present invention, a linear array of individual receptacles 162 are integrally coupled together by the connecting rib structure 164.

The broadest aspects of the present invention, however, contemplate a reaction receptacle apparatus 260, as shown in FIGURE 15, which comprises a single receptacle 262 having an open-mouth 261 and a connected contactlimiting element holding structure, such as tiplet holding structure 276, attached to the receptacle 262.

In the embodiment illustrated in FIGURE 15, tiplet holding structure 276 includes a tiplet receiving orifice 279, a longitudinal slot 278, and an end-face *ee.

277 forming a portion of an annulus. Alternatively, r. the contact-limiting element holding structure may be in the form of tiplet holding structure 176 of FIGURE 1, in which no longitudinal slot is formed therein and 20 in which a plurality of longitudinally extending raised ribs 154 (see FIGURE 3) are formed on the inner surface O O of the orifice 150.

A further alternate embodiment of the reaction receptacle apparatus of the present invention is 25 generally designated by reference number 360 in FIGURE 16. As shown in the drawing, the preferred embodiment of reaction receptacle apparatus 360 includes a plurality of individual receptacles 362, each having an -28open receptacle mouth 361. The most preferred embodiment of the reaction receptacle apparatus 360 includes five individual receptacles 362. Individual receptacles 362 are connected to one another by a connecting rib structure 364.

Reaction receptacle apparatus 360 is in most respects identical to the reaction receptacle apparatuses described above and shown in Figures i, 4, and 5, except that reaction receptacle apparatus 360 does not include contact-limiting holding structures 176 (76) associated with each individual receptacle 362. Nor does reaction receptacle apparatus 360 include a contact-limiting element, such as tiplet 170,

S.

associated with each individual receptacle 362.

Reaction receptacle apparatus 360 also preferably includes a label-receiving structure 374 having an upper portion 377 and a lower portion 375 cooperating so as to define a flat label-receiving surface 376. A vertical gusset wall 378 extends between the upper 20 portion 377 of label-receiving structure 374 and the ee r 0e outer wall of the endmost individual receptacle 362.

In addition, reaction receptacle apparatus 360 SeeS includes an arcuate shield structure 385 having an upper portion 369 and a lower portion 373. A receptacle apparatus manipulating structure 366 includes a transverse piece 367 connected to the S arcuate shield structure 385 by means of a plate 368 extending between upper portion 369 of arcuate shield -29structure 385 and transverse piece 367, and a gusset wall 383 extending between the lower portion 373 of the arcuate shield structure 385 and the transverse piece 367 of the receptacle apparatus manipulating structure 366. As with the previous embodiments, the transverse piece 367 and the lower portion 373 of the arcuate shield structure 385 preferably have mutually-facing convex surfaces, and the surfaces may include vertical arcuate ridges 371 and 372, respectively. The receptacle apparatus manipulating structure 366 and the arcuate ridges 371 and 372 of the reaction receptacle apparatus 360 serve the same function as the receptacle apparatus manipulating structure 166 and the raised Se arcuate ribs 171 and 172 described above.

15 The reaction receptacle apparatus 360 may further 0**0 ooo include connecting walls 380 extending between adjacent :.:00 individual receptacles 362 at upper portions thereof above the connecting rib structure 364. In addition, a gusset wall 382 may be provided between the endmost 20 individual receptacle 362 and the arcuate shield 0000.0 So° "structure 385. Finally, the reaction receptacle 0000 apparatus 360 may further include lateral ribs 390 extending vertically along the outer surfaces of diametrically opposed positions of upper portions of 25, the individual receptacles 362. The lateral ridges 390 of the reaction receptacle apparatus 360 serve the same function as do the lateral ribs 190 described above.

While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention is not to be limited to the disclosed embodiments, but, on the contrary, it is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. Thus, it is to be understood that variations in the particular parameters used in defining the present invention can be made without departing from the novel aspects of this invention as defined in the following claims.

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Claims (14)

1. A receptacle apparatus for use in performing a chemical or biological assay, the apparatus comprising: a plurality of aligned receptacles, each receptacle comprising a hollow body, an open top end and a closed bottom end, wherein the receptacles are capable of interacting with a substance transfer device constructed and arranged to dispense fluid into or withdraw fluid from one or more of the receptacles; one or more contact-limiting element holding structures, each contact- limiting element holding structure being adjacent the open top end of at least one of the receptacles and comprising a body having an orifice therein for removably receiving a contact-limiting element; and a connecting rib structure fixedly connecting the receptacles to one another, wherein the receptacles, the contact-limiting element holding structures and the connecting rib structure form an integral piece. S 2. The receptacle apparatus of claim 1, wherein the receptacles have S• different shapes or sizes. O be i•6i 0* S 20 3. The receptacle apparatus of claim 1, wherein the receptacles have the same shape and size.

4. The receptacle apparatus of any one of claims 1 to 3, wherein each S•receptacle comprises a generally cylindrical body. 0000 S The receptacle apparatus of any one of claims 1 to 4, wherein the receptacles are generally parallel to one another. iI 6. The receptacle apparatus of any one of claims 1 to 5, wherein the 30 receptacles are arranged to be simultaneously engageable by the substance transfer device to permit the substance transfer device to dispense fluid into or withdraw fluid from each of the receptacles simultaneously. W:.ckskaik speCeslIV 735267 claims.doc 33

7. The receptacle apparatus of any one of claims 1 to 6, wherein each contact-limiting element holding structure comprises a generally cylindrical body.

8. The receptacle apparatus of any one of claims 1 to 7, wherein the connecting rib structure defines generally straight edge surfaces extending along opposite sides of the aligned receptacles and having generally flat shoulders facing toward the bottom ends of the receptacles.

9. The receptacle apparatus of claim 8, wherein one end of the connecting rib structure is bent upwardly along opposite sides of the aligned receptacles to define upwardly sloped edge surfaces extending from the generally straight edge surfaces.

10. The receptacle apparatus of any one of claims 1 to 9 further comprising a label-receiving structure having a surface for affixing human and/or machine readable information thereto. SOS. *l S 8005

11. The receptacle apparatus of any one of claim 1 to 10 further comprising 20 a receptacle apparatus manipulating structure which is constructed and arranged to be engaged by a receptacle apparatus manipulating device to manipulate the receptacle apparatus. 25 12. The receptacle apparatus of any one of claims 1 to 11, wherein at least 25 one of the receptacles has ribs extending outwardly from opposed outer surfaces thereof, the opposed surfaces corresponding to the opposite sides of the aligned receptacles.

13. The receptacle apparatus of any one of claims 1 to 12 further comprising 30 a lid structure constructed and arranged to enclose one or more of the receptacles. W:%dskaflkIpec.eSeDIV 735267 daims.doc 34

14. The receptacle apparatus of any one of claims 1 to 13 further comprising one or more contact-limiting elements, each contact-limiting element being associated with one of the contact-limiting element holding structures, wherein the contact-limiting elements are constructed and arranged to be operatively engaged by the substance transfer device to limit contact between at least a portion of the substance transfer device and fluid dispensed into or withdrawn from one or more of the receptacles by the substance transfer device. The receptacle apparatus of claim 14, wherein each of the contact- limiting elements comprises: a tubular body having a proximal end, a distal end and an inner bore extending from the proximal end to the distal end; and a peripheral flange disposed about an outer periphery of the tubular body, wherein each contact-limiting element is constructed and arranged to be frictionally secured onto a free end of a tubular element of the substance transfer device when the contact-limiting element is engaged by the tubular element.

16. The receptacle apparatus of claim 15, wherein a portion of the tubular body proximate the distal end is formed at an angle with respect to a longitudinal axis of the tubular body. 0 S OeeO 0 96 0 *t .o a. a *0 a. .0 AS*% 25 *0b0 O 0 4 sel l 30

17. The receptacle apparatus of claim 15 or 16, wherein: the contact-limiting element holding structure has a peripheral end face oriented transversely to an axis of the orifice of the contact-limiting element holding structure; and the peripheral flange of the contact-limiting element is in contact with the peripheral end face of the contact-limiting element holding structure when the tubular body of the contact-limiting element is fully inserted into the orifice of the contact-limiting element holding structure.

18. The receptacle apparatus of claim 14, wherein the contact-limiting element is a disposable protective tip. W: cska nlispeciesDIV 735267 claims.doc

19. The receptacle apparatus of claim 18, wherein the disposable protective tip is a pipette tip. The receptacle apparatus of claim 14, wherein the contact-limiting element is a tiplet.

21. An apparatus according to claim 1 substantially as hereinbefore described with reference to any of the examples. DATED: 21 September, 2001 PHILLIPS ORMONDE FITZPATRICK Attorneys for: GEN-PROBE INCORPORATED 0 3 W:\ciska\nklspecesDIV 735267 claims.doc