MICROSAMPLE CUP FOR LIQUID ANALYSIS SYSTEMS

Abstract: A microsample cup (32) comprises an outer cup body member (34), and an inner sample liquid vessel (36) disposed and supported therewithin. An integral sample liquid over­ flow reservoir (46) is provided to surround the inner sample liquid vessel so that precise filling of the vessel can be achieved by filling to its maximum capacity, any excess over­ flowing into the reservoir. The outer cup body member pre­ ferably extends significantly above and/or below the inner sample liquid vessel.

Description: This invention relates to a microsample cup which is particularly, but not exclusively, for use in automated sample liquid analysis systems. In automated sample liquid analysis systems, microsample cups are used for containing small quantities of liquids (eg. from 200 to 500 microlitre quantities) such as blood or other sample fluids. WO-A-8400418 describes a microsample cup container comprising an outer body member, an inner sample liquid vessel disposed within the outer body member and spaced therefrom, and a support member integral with the outer body member and the inner sample vessel and operable to support the inner sample vessel from the outer body member. It is important that, when ready for use in an analysis system, the microsample cups all contain the same amount of sample liquid. We have now devised a cup whereby this can be reliably and simply achieved. According to the present invention there is provided a sample liquid cup for the containment of a sample liquid comprising: an outer body member, an inner sample liquid vessel disposed within said outer body member and spaced therefrom, and a support member integral with said outer body member and said inner sample vessel and operable to support said inner sample vessel from said outer body member, characterised in that said outer body member, inner sample liquid vessel and said support member respectively comprise means for forming a sample liquid overflow reservoir between said outer body member and said inner sample liquid vessel which surrounds said inner sample liquid vessel to receive liquid overflowing from said inner sample liquid vessel. In use, the precise filling of the inner sample liquid vessel to a maximum predetermined sample liquid level coincident with the maximum sample liquid capacity of said inner sample liquid vessel is facilitated by the overflow of sample liquid introduced into said inner sample liquid vessel in excess of that maximum capacity into said sample liquid overflow reservoir from said inner sample liquid vessel. The invention also provides a method of providing a precise predetermined volume of liquid by filling a sample liquid vessel until liquid overflows therefrom characterised in that the sample liquid vessel is part of a sample liquid cup of the invention, and the liquid overflow is collected in the overflow reservoir thereof. The microsample cup of the invention is particularly adapted for use in contemporary automated sample liquid analysis systems which operate to automatically sequentially analyze sample liquids ranging in volume from 200 to 500 microlitres. In a preferred embodiment, the microsample cup comprises a generally cylindrical outer cup body member, and a generally cylindrically cup-shaped inner sample liquid vessel supported therefrom generally concentrically therewithin by an integral, generally ring-shaped support member. Contiguous wall surfaces of the outer body member, inner sample liquid vessel and support member cooperate to form a generally U-shaped sample liquid overflow reservoir which completely surrounds the inner sample liquid vessel, whereby the precise filling of the inner sample liquid vessel to a predetermined maximum level coincident with the maximum sample liquid capacity of the inner sample liquid vessel is greatly facilitated by the fact that any sample liquid in excess of that capacity introduced into the inner sample liquid vessel will simply overflow therefrom into the sample liquid reservoir. The outer body member preferably extends significantly above the upper edge of the inner sample liquid vessel to shield the same from relative movement of the ambient air thereby inhibiting sample liquid evaporation therefrom, and reducing the probability of accidental contact by the fingers of the operator with the sample liquid. This also reduces the probability of sample liquid spillage from the microsample cup. The outer body member may also extend significantly below the bottom of the inner sample liquid vessel to facilitate manual handling of the microsample cup. Among the known prior art cups is the 500 microlitre microsample cup currently marketed by us. Although this is entirely satisfactory for use with contemporary automated sample liquid analysis systems, it does not include provision for sample liquid overflow and this renders the precise filling to a predetermined level somewhat difficult especially in view of the very small sample liquid quantities in question. In addition, this prior art microsample cup, when properly filled as required to the predetermined maximum level, is somewhat prone to sample liquid evaporation attendant the not insubstantial residence time of the filled microsample cup on the automated sample liquid analysis system because this microsample cup contains and presents the sample liquid in such manner that the sample liquid surface is substantially fully exposed to the ambient air. The problem of evaporation is significant especially when dealing with very small available sample liquid quantities. Also, this substantial exposure of the sample liquid surface, and the attendant increase in the probability of accidental contact by the fingers of the operating personnel therewith of late increasingly leads to significant personnel problems in those instances wherein the sample liquid in question is, for example, a blood sample which might be a carrier of an infectious disease. If prior art cups are over-filled, as can readily occur in the absence of very careful attention to cup filling on the part of the operating personnel the residence time in the liquid of the very precisely fixed-travel sample liquid aspiration probe is increased, and this can significantly degrade sample liquid aspiration accuracy, and accordingly the overall accuracy of the sample liquid analysis results. Also, the substantial exposure of the surface of the sample liquid to the ambient air in this prior art microsample cup, and the fact that the liquid surface is in close proximity to the upper cup edge and there is no provision for the collection of sample liquid overflow, can be particularly conducive to sample liquid spillage from the cup, and especially in those instances wherein the cup is filled beyond the predetermined maximum sample liquid level. The 250 microlitre microsample cup currently marketed by the Fisher Scientific Company of Pittsburgh, Pennysylvania, although also satisfactory for use with contemporary automated sample liquid analysis systems, is very similar in essential structural and functional characteristics to our above-described prior art microsample cup. It is thus prone to essentially the same operational problems. Among the advantages of the cups of the present invention are: 1. the cup is readily and conveniently fillable to a precisely determined maximum level. 2. the cup be made so as to greatly inhibit evaporation of the sample liquid into the ambient air. 3. the cup can be made so as to greatly inhibit spillage of the sample liquid therefrom. 4. the cup can be made so as to greatly inhibit contact by the fingers of the cup operating personnel with the sample liquid contained therein. 5. the cup can be of particularly simple and economical one-piece construction. In order that the invention may be more fully understood, reference is made to the accompanying drawings, wherein: FIG. 1 is a top plan view of a prior art microsample cup; FIG. 2 is a vertical cross-sectional view taken generally along line 2-2 of FIG. 1; FIG. 3 is a top plan view of a microsample cup of the present invention; and FIG. 4 is a vertical cross-sectional view taken generally along line 4-4 in FIG. 3. Referring initially to FIGS. 1 and 2 of the drawings, a microsample cup representatively configured and operable in accordance with the principles of the prior art is indicated generally at 10, and comprises an outer, generally cylindrical cup body member 12, and an inner sample liquid vessel 14 formed integrally therewith and supported therefrom generally concentrically therewithin. A microsample cup mounting ring as indicated at 16 is formed as shown on the outer body member 12 to extend radially outward therefrom for purposes of mounting the cup 10 on a carrier block or like microsample cup supporting and indexing device 18 of an automated sample liquid analysis system. The sample liquid analysis system, which may for example take the form of a highly advanced contemporary version of the sequential multiple sample liquid automated analysis system disclosed in US-A- 3,241,432, includes a very precisely operable sample liquid aspiration probe as indicated at 20. The system is operable to present each of a series of the sample liquid-containing microsample cups 10 in turn to the aspiration probe 20 for the sequential aspiration thereby of a plurality of precisely predetermined, like sample liquid quantites therefrom, and supply to the analysis system for precise automated sample liquid quantity analysis with regard to one or more sample liquid constituents. To this effect, small volumes of the sample liquids in question, for example 200 microlitres, must of course first be disposed in the inner sample liquid vessel 14 of each of the microsample cups 10. For representative use of the microsample cup 10 attendant automated blood sample analysis, the small available blood sample volumes such as from prematue babies or geriatric patients, are typically procured by capillary stick at the finger or heel of the donor, processed as required by centrifugation of the capillary to separate the blood sample plasma from the blood sample cells, and the separated small blood plasma sample volume is then placed via the capillary in the inner sample liquid vessel 14. The sample liquid aspirating probe 20 in FIG. 2 travels between the position thereof as shown by solid lines in FIG. 2 (wherein the inlet end of the probe is immersed in the blood sample 22 for aspiration thereof and supply to the analysis system and the probe position as shown in dashed lines in FIG. 2 (wherein the probe 20 is completely out of the microsample cup 10 and "between" blood sample liquid aspirations). This travel distance is very precisely fixed and unvariable. Also, the acceleration with and velocity at which the aspirating probe 20 can be moved between those positions when the probe is to any extent immersed in the blood sample liquid 22, are very strictly limited by factors having a direct bearing on the requisite very high degree of blood sample aspiration accuracy, it will be clear to those skilled in this art that it is of vital importance to the overall accuracy of the blood sample liquid analysis results that the inner sample liquid vessel 14 of each of the microsample cups be filled as described with blood sample liquid to exactly the same precisely predetermined maximum level as illustrated by the solid line blood sample liquid meniscus 24 in FIG. 2. More specifically, it will be clear that filling of the inner vessel 14 with blood sample liquid above that carefully predetermined maximum level (e.g. to the dashed line 26 in FIG. 2) will increase the residence time of the aspirating probe 20 in the same to extend into those time periods when the probe is being accelerated and/or moved in the interests of high speed overall analysis system operation at rates and/or velocities which exceed those permitted by the dynamics of the probe-blood sample liquid interaction. Filling of the inner sample vessel 14 with the blood sample liquid 22 below that level (e.g. to phantom line 28 in FIG. 2) can ultimately result upon repeated blood sample liquid quantity aspiration in less than the required blood sample liquid volume remaining in the inner sample vessel 14 for subsequent aspiration and analysis as required. Thus, although visible indicia such as guide lines or the like as indicated at 30 in FIG. 1 may be formed in the body of the inner sample liquid vessel 14 to assist the operator in filling the vessel to exactly the same maximum predetermined level in each instance, it will be readily understood by those skilled in this art that the very small sample liquid volumes, and commensurately small dimensions of the inner sample liquid vessel 14 make this a somewhat difficult and tedious task, and especially in those representative instances as discussed hereinabove wherein a large plurality of the microsample cups 10 must be precisely filled as described in relatively rapid succession in preparation for a typical "run" of an automated blood sample liquid analysis system. This is to say that errors can and do occur, and that the overall accuracy of the blood sample liquid analysis results can and does suffer as a result. In addition to the above, it will be clear that since the surface of the blood sample liquid 22 in the inner sample liquid vessel 14 is, in any event, substantially exposed to the ambient air, evaporation of the sample liquid is promoted. This can, of course, be significant in view of the very small sample liquid volumes involved. Although a microsample cup cover can be provided to cover a plurality of the microsample cups 10 and inhibit evaporation therefrom, it will be clear that the disposition of the surface of the blood sample liquid 22 as shown very close to the upper edge of the inner sample liquid vessel 14, and especially in those instances wherein the same is filled as indicated by the meniscus 26 above the maximum predetermined level, promotes smearing or the like of the blood sample liquid 22 on the underside of that evaporation cover with resultant increase in the probability of contact by the fingers of the operator with the blood sample liquids upon removal of the evaporation cover from the microsample cups 10. This increased probability of contact with the blood sample liquids can lead to significant operator personnel problems, particularly in those instances wherein the blood sample liquids in question might be carriers of an infectious disease. Also, it will be clear that the disposition of the blood sample liquid surface very close to the upper edge of the microsample cup 10 as a whole, will, in any event, promote spillage of the blood sample liquid therefrom, especially in those instances wherein the prior art microsample cup 10 is filled above the maximum predetermined level. Referring now to FIGS. 3 and 4, a microsample cup of the invention is indicated generally at 32. It comprises a generally cylindrical outer cup body member 34, and a generally cylindrically cup-shaped inner sample liquid vessel 36 supported therefrom generally concentrically therewithin by an integral, generally ring-shaped support member 38. FIG. 4 makes clear that the outer body member 34 extends significantly above and below the inner sample liquid vessel 36. A microsample cup mounting ring 39 extends radially outwardly of the outer body member 34 for mounting the cup 32 on a carrier block 18 of an automated sample liquid analysis apparatus. FIGS. 3 and 4 show that the inner wall surface 40 of the outer cup body member 34, and the outer wall surface 42 of the inner sample liquid vessel 36, cooperate with the upper wall surface 44 of the integral support member 38 to form a generally U-shaped sample liquid overflow reservoir as indicated at 46 which completely surrounds the upper edge 48 of the inner sample liquid vessel 36. As a result, it will be immediately clear to those skilled in this art that filling by the operator of inner sample liquid vessel 36 with the blood sample liquid 22 to its carefully predetermined maximum level --which will coincide with the filling of the vessel to its full capacity as illustrated by the blood sample liquid meniscus 50 in FIG. 4-- is greatly facilitated because any blood sample liquid in excess of that capacity, within reasonable limits of course, will simply overflow the inner sample liquid vessel 36 for flow into and safe containment in the sample liquid overflow reservoir 46. A representative quantity of blood sample liquid overflow is illustrated at 52 in sample liquid overflow reservoir 46 in FIG. 4. As a result, and although great care and full attention to cup filling detail are still required on the part of the operator for filling to precisely the maximum predetermined level, it will be clear that the chances for error attendant the same are advantageously greatly reduced by the teachings of this invention. Thus, the operator can be instructed to fill each of the microsample cups 32 until just the very slightest and thus analytically inconsequential although nonetheless readily visibly discernible, quantity of the blood sample liquid appears in the sample liquid overflow reservoir 46, thus ensuring in each instance that the inner sample liquid vessel 36 of the microsample cup 32 in question has been filled by the blood sample liquid 22 to precisely its predetermined maximum level. Thus, the blood sample liquid aspirating probe as again indicated at 20 in FIG. 4 will have exactly the same maximum residence time in the blood sample liquid quantities 22 in each of the plurality of the microsample cups 32 under discussion. In this way, consistent operation of the aspirating probe 20 at maximum accelerations and velocities for the probe operating time periods outside that maximum blood sample liquid residence time of the probe, and commensurate in each instance with high speed operation and sample analysis rate of the analysis system, can be accomplished for all of the microsample cups 32 attendant a blood sample liquid analysis "run" of the sample liquid analysis system, all without realistic possibility of sacrifice in the requisite very high degree of blood sample liquid aspiration accuracy. Regarding blood sample liquid evaporation, it will be clear that the generally straight and vertically oriented inner wall surface 40 of the outer cup body member 34 which completely surrounds the upper edge 48 of the inner sample liquid vessel 36 and the significant vertical extent of that wall surface 40 above the upper vessel edge 48, both as clearly illustrated by FIGS. 3 and 4, advantageously operate to substantially shield the surface of the blood sample liquid 22 at the upper edge of the inner sample liquid vessel 36 from the natural and microsample cup indexing-induced relative movement of the ambient air, whereby blood sample liquid evaporation from the inner sample liquid vessel 36 is greatly inhibited. Once saturation by blood sample liquid molecules of the relatively stagnant ambient air in the shielded cup space 54 above the inner sample liquid vessel 36 occurs, very little if any further evaporation of the blood sample liquid 22 from the vessel 36 will take place. An additionally significant advantage of the microsample cup 32 of the invention resides in the fact that the substantial extent of the inner wall surface 40 of the outer cup body member 34 above the surface of the blood sample liquid 22 in the inner sample vessel 36 operates to very greatly reduce the probability of direct contact by the fingers of the operator with the blood sample liquid in the inner vessel. This, also very greatly reduces the probability of smearing of the blood sample liquid from the microsample cup on an evaporation cover of the like as may be used to cover a plurality of the same, thus reducing to a like degree the probability of subsequent contact by the fingers of the operator with the blood sample liquid from that source. Also, the probability of blood sample liquid spillage from the microsample cup 32 as a whole is, within reasonable limits, virtually eliminated by the substantial extent of the outer cup body member inner wall surface 40 above the upper support member wall surface 44 which froms the bootom of the sample liquid overflow reservoir 46; and this, of course, further promotes compliance with essential standards of clinical cleanliness as are required attendant blood sample liquid handling and automated analysis. As a result of all of these factors, the probability of personnel problems arising from accidental contact by the operator(s) with the blood sample liquids in question is, again within reasonable limits, advantageously reduced to an absolute minimum by the teachings of the invention. A representative sample liquid aspirating probe with which the new and improved microsample cup 32 of the invention is particularly adapted for use attendant automated blood sample liquid analysis is that disclosed in United States Patent 4,121,466. Although the essential dimensions of the new and improved microsample cup 32 of the invention may, of course, vary in accordance with the requirements of the application to which the same is to be put, the extent of the inner wall surface 40 of the outer body member 34 above the upper edge 48 of the inner sample liquid vessel 36 is preferably made at least equal to the inner diameter of that sample liquid vessel; and it will be clear that the extension as shown and described of the outer body member 34 to not insubstantial extents both above and below the inner sample liquid vessel 36 adds significantly to the overall vertical dimension of the microsample cup 32, and thus contributes materially to increased ease of manual cup handling by the operator(s). Representative dimensions for the new and improved microsample cup 32 of our invention are: an overall height of the outer body member 34 of approximately 25 millimetres; an internal diameter at the upper edge of the outer body member 34 of approximately 10 millimetres; an overall depth of the inner sample liquid vessel 36 of approximately 10 millimetres; an internal diameter at the upper edge 48 of the inner sample liquid vessel 36 of approximately 6 millimetres; a distance between the upper edge 48 of the inner sample liquid vessel 36 and the upper edge of the outer body member 34 of approximately 8 millimetres; and a distance between the bottom of the inner sample liquid vessel 36 and the lower edge of the outer body member 34 of approximately 7 millimetres. A representative capacity for the inner sample liquid vessel 36 is 250 microlitres of sample liquid. Fabrication of the microsample cup 32 is readily and economically accomplished by, for example, high speed injection molding of an appropriately chemically inert plastic material, for example polyethylene, thus rendering the microsample cup economically disposable after but a single usage. Although disclosed hereinabove by way of representative example in the context of use for automated blood sample liquid analysis, it will be clear to those skilled in this art that the microsample cup 32 is by no means limited thereto but, rather, can be used with advantageous effect with other and different biological sample liquids, for example urine samples, or with a wide variety of other and different non-biological sample liquids.

Claims: 1. A sample liquid cup (32) for the containment of a sample liquid (22) comprising: an outer body member (34), an inner sample liquid vessel (36) disposed within said outer body member and spaced therefrom, and a support member (38) integral with said outer body member and said inner sample vessel and operable to support said inner sample vessel from said outer body member, characterised in that said outer body member, inner sample liquid vessel and said support member respectively comprise means for forming a sample liquid overflow reservoir (46) between said outer body member and said inner sample liquid vessel which surrounds said inner sample liquid vessel to receive liquid overflowing from said inner sample liquid vessel. 2. A sample liquid cup (32) according to claim 1, wherein said outer body member (34), inner sample liquid vessel (36) and support member means (38) which form said sample liquid overflow reservoir (46) respectively comprise contiguous wall surfaces (40,42,44) of said outer body member, inner sample liquid vessel and support member. 3. A sample liquid cup (32) according to claim 1 or 2, wherein said outer body member (34) is generally cylindrical, said inner sample liquid vessel (36) is generally cylindrically cup-shaped and is disposed within said outer body member generally concentrically thereof, and wherein said support member (38) is generally ring-shaped. 4. A sample liquid cup (32) according to claim 1,2 or 3, wherein said outer body member (34) extends significantly above said inner sample liquid vessel (36) to reduce evaporation losses from said inner sample liquid vessel. 5. A sample liquid cup according to claim 3, wherein said outer body member (34) extends above said inner sample liquid vessel (36) to an extent at least equal to the inner diameter of said sample liquid vessel to reduce evaporation losses from said inner sample liquid vessel. 6. A sample liquid cup (32) according to any of claims 1 to 5, wherein said sample liquid cup is a microsample cup with said inner sample liquid vessel (36) having a sample liquid capacity in the range of from 200 to 500 microlitres. 7. A sample liquid cup (32) according to any of claims 1 to 6, wherein said outer body member (34) extends significantly below said inner sample liquid vessel (36) to facilitate manual handling of said sample liquid cup. 8. A microsample liquid cup (32) according to any of claims 1 to 7, for use in an automated analysis system. 9. A method of providing a precise predetermined volume of liquid by filling a sample liquid vessel (36) until liquid overflows therefrom characterised in that the sample liquid vessel (36) is part of a sample liquid cup as claimed in any of claims 1 to 8, and the liquid overflow is collected in the overflow reservoir (46) thereof.

Inventors: UFFENHEIMER, KENNETH FRANK
Applicants: TECHNICON INSTRUMENTS CORPORATION(A DELAWARE CORPORATION)
Application year: 1987
Main classification: B01L3
IPC codes: B01L3, G01N35