WO2023247795A1

WO2023247795A1 - Measuring device and method of use thereof

Info

Publication number: WO2023247795A1
Application number: PCT/EP2023/067256
Authority: WO
Inventors: Robert John Fraser REARDON; Benjamin CAHOON; Benjamin S. Larson
Original assignee: Reardon Robert John Fraser
Priority date: 2022-06-24
Filing date: 2023-06-26
Publication date: 2023-12-28

Abstract

A measuring device for insertion in a cooperating laboratory tube is described, wherein the device has a first, upper surface, a second, lower surface, and a circumferential edge, wherein the circumferential edge is shaped to substantially match a portion of the inner wall of the laboratory tube, wherein the device, when installed in the laboratory tube, seats in a predetermined position in spaced separation from the bottom of the tube at a pre-determined distance therefrom, and wherein the first and second surfaces are linked by a passage through the device from the upper surface to the lower surface. The device is suitable for use with biological samples, including urine. Accordingly, methods of use of the device and a system for manufacturing the device are also described.

Description

Measuring Device and Method of Use Thereof

The present invention relates to apparatuses and methods for measuring specific quantities of liquids or suspensions held within vessels. In particular, the invention relates to vessels suitable for centrifugation and/or use in a laboratory. In particular, devices of the invention are inserted into the vessels such that they cause the retention of a specific and measurable volume of liquid or suspension when the excess or remaining liquid or suspension is removed. Accordingly, the invention also relates to methods for use of the product of the invention in measuring specific quantities of liquid or suspension in the context of vessels suitable for centrifugation and/or laboratory use (e.g., laboratory tubes). The invention also considers methods of manufacture of the products of the invention and use of the products of the invention for the adaptation of diagnostic tests and techniques.

The centrifuge and the disposable tubes used for centrifuges are central to biological research and analysis. They are an essential part of a myriad of diagnostic techniques and tests.

The ability of a centrifuge tube combined by acceleration under centrifugation through pellet samples such that the desired fraction of a liquid or suspended material is rendered conveniently available is used in virtually all facets of biological research and biological testing.

However, all tests are only as accurate and reliable as the volumes of samples and reagents on which they depend. Erroneous results can arise from use of too much or too little sample and lead to skewed or inexact results that cannot be combined between standardised data sets. Such inconsistencies are exacerbated by centrifugation of biological samples and thus the concentration of particular fractions of sample in smaller sub-volumes of the sample. This can lead to inaccuracies in true concentration measurements and thus inconsistently effective diagnosis.

Heretonow this has been less of a problem because data produced within a laboratory would be expected to be internally consistent. Furthermore, many tests depend on other techniques such as microscopy and thus there are independent methods of ascertaining a particular result or confirming an unexpected or difficult result.

However, there is a move towards large reference laboratories who will take in samples from a wide variety of places and must produce results that can be comparable and standardised. Furthermore, such results are suitable for automated testing and diagnosis which offers the prospect of more rapid and reliable testing, as well as being less costly.

Thus, there exists a need for improved measuring devices that allow for the precise measurement of volumes within laboratory tubes and centrifuge tubes particularly, so that the volume of concentre or eluate can be yielded reliably and thus allow or contribute to the provision of better standardised tests and testing procedures.

It is therefore an object of the invention to provide an improved method of measuring quantities of liquid in laboratory tube. It is a further object of the invention to provide apparatus that can be used to adapt a laboratory tube in order that a predetermined volume of a liquid sample processed in such a vessel can be accurately and conveniently measured and separated from the remaining liquid. It is a further object of the invention that the apparatus should be suited for processing of the liquid sample by way of centrifugation.

The invention provides a measuring device for insertion in a cooperating laboratory tube, wherein the device has a first, upper surface, a second, lower surface, and a circumferential edge, wherein the circumferential edge is shaped to substantially match a portion of the inner wall of the laboratory tube, wherein the device, when installed in the laboratory tube, seats in a predetermined position in spaced separation from the bottom of the tube at a pre-determined distance therefrom, and wherein the first and second surfaces are linked by a passage through the device from the upper surface to the lower surface.

The invention also provides method of measuring a volume of liquid comprising the steps of: seating a measuring device as disclosed herein in a cooperating laboratory tube to define a volume between the base of the laboratory tube and the lower surface of the measuring device; introducing an amount liquid or suspension to the laboratory tube such that the volume is filled with liquid or suspension; and decanting the liquid retained above the upper surface of the measuring device from the laboratory tube, while retaining the liquid or suspension filling the volume.

The invention further provides a system comprising an injection moulding tool for manufacturing a measuring device as disclosed herein.

The invention also provides a kit comprising a measuring device as disclosed herein, together with a cooperating laboratory tube, and optionally pre-installed in the cooperating laboratory tube.

In the context of the present disclosure, the term “for” is defined to mean “suitable for” the purpose, method or objective defined in conjunction with this term.

The terms seats and seated are defined in the present context to mean to be fitted in position. Further, in the context of the present disclosure that means that a device is fitted in the correct and/or predetermined position in the cooperating laboratory tube.

The measuring device of the present invention is for cooperative use with a compatible laboratory tube. That is, the measuring device has suitable outer dimensions such that it can be inserted in a laboratory tube and the surface all surfaces of the measuring device that abuts the inner walls of the laboratory tube match the contours of the laboratory tube. Preferably, the measuring device has a plug fit at a predetermined position in the laboratory tube. In this way, the position in which the measuring device is seated in the laboratory tube can be altered in order that a specific volume can be defined in the space defined and/or substantially bounded by the lower surface of the measuring device and the walls of the laboratory tube. Thus, advantageously, the form of the device can be designed to measure any particular desired volume. Laboratory tubes are conveniently used for holding and processing volumes of liquids. These can be samples of biological origin or other liquids. Accordingly, the definition of liquid in the context of the present disclosure includes pure liquids and also suspensions of matter in liquids. Accordingly, the measuring device disclosed herein may be suitable for operation in the context of liquids and/or suspensions.

Thus, the apparatus and methods disclosed herein are suitable for measurement of biological samples, e.g. urine, blood, lymph, plasma, cerebrospinal fluid, saliva. Preferably, the sample is a urine sample. It is noted that such samples may have solid matter suspended therein. This solid matter may include cells, debris and/or precipitates, e.g. a urine sample may comprise uric acid crystals.

The passage through the device from the upper surface to the lower surface means that the below the lower surface and the space be above the upper surface are in fluid connection. Thus the passage may be open. In this context the passage being open means that the passage is unimpeded by valves or means for temporarily blocking the passage. Thus, preferably, the measuring device is substantially ring-shaped or annular.

The advantage of having the passage be unimpeded by a valve or other means for mechanically blocking or closing the passage is that the measuring device can be manufactured simply by techniques such as injection moulding of plastics material to produce the measuring devices in large numbers. This simplicity of manufacture has the attendant advantage that the measuring device may be disposable.

The upper surface of the measuring device may be substantially perpendicular to the longitudinal axis of the laboratory tube. The advantage of this perpendicular arrangement is that when the tube is inverted to decant the liquid that is not to be retained by the measuring device, the surface tension retaining the measured liquid is most stably maintained by keeping the portal to the passage level/flat. Thus the probability of losing sample from the retained volume is minimised.

Similarly, The lower surface of the measuring device may be substantially perpendicular to the longitudinal axis of the laboratory tube. The advantage of this arrangement is that it simplifies calculation of the position of the measuring device in the context of the cooperating laboratory tube and bus accuracy of measurement of the desired retained volume of liquid.

The volume of the retained volume of liquid in the reservoir defined by the lower surface of the measuring device and the lower inner wall of the cooperating laboratory tube may be 5 millilitres (ml), 4 ml, 3 ml, 2.5 ml, 2 ml, 1 .5 ml, 1 ml, 500 microlitres (pl), 300 pl, 200 pl, 100 pl, or 50 pl. Preferably, the retained volume of liquid in the reservoir is 300 pl.

The laboratory tube may be of the standard volumes and/or dimensions of laboratory tubes produced by Eppendorf®, Stirling®, Falcon®; or generic versions and/or variants thereof. Thus, advantageously, the measuring device can be made to be compatible with a wide range of standard and widely used laboratory tubes. Further, advantageously, the measuring device can be made to be compatible with essentially any laboratory tube.

Accordingly, the laboratory tube may be round, elliptical or circular in transverse crosssection. Preferably, the laboratory tube is substantially circular in transverse crosssection.

Thus the laboratory tube may be designed to have a total volume of 50 ml, 50 ml, 5 ml, 2 ml, 1.5 ml or 1 ml.

The measuring device may be made of plastics material. Preferably, the plastics material is injection moulded, however, the plastics material may be 3-D printed. The measuring device may be manufactured from one or more plastics material selected from the following list: acrylic (PMMA); acrylonitrile butadiene styrene (ABS) polyamide (PA; nylon); polycarbonate (PC); polyethylene (PE); polyoxymethylene (POM); polypropylene (PP); polystyrene (PS); thermoplastic elastomer (TPE); or thermoplastic polyurethane (TPU). Preferably the plastics material selected is polypropylene. Preferably the plastics material selected is polyethylene, most preferably the plastic material is high density polyethylene (HDPE). The plastics material may be biologically inert. In this context biologically inert means that the plastics material does not react with biological material that it comes into contact with. Accordingly, such a biologically inert material does not affect the results of tests, or assays carried out on biological samples or liquids that it is brought into contact with. More preferably these are plastics materials which are characterised by low absorbance of protein, such as polypropylene and/or polycarbonate.

The passage through the measuring device from the upper service to the lower surface may be straight. Preferably, the passage is parallel with the central axis of rotation of the cooperating laboratory tube. Most preferably, the passage is co-linear with the central axis of rotation of the cooperating laboratory tube

The walls of passage may taper inwards as the passage runs from the upper surface to the lower surface of the measuring device. The tapering may be linear, e.g. the inner surface may have the form of a truncated cone. Alternatively, the tapering may be discontinuous, e.g. to provide a funnel surface whereby the ball of the final at the upper surface narrows to a conduit passage running to the lower surface. The advantage of such tapering is that solid matter or precipitate is not retained on the flat upper surface, but is more efficiently directed through the passage.

The passage may be curved with respect to the central axis of rotation of the cooperating laboratory tube. Alternatively, or in addition, the passage may be angled with respect with the central axis of rotation of the centrifuge tube. Passages with such configurations may offer the advantage of better retention of precipitated and/or solid matter in the liquid sample when the supernatant is decanted by inversion of the laboratory tube.

Seating of the measuring device in the cooperating laboratory tube may be achieved via axial pressure on the measuring device towards the base of the cooperating laboratory tube. Preferably, the force required for this seating is provided by centrifugation of the laboratory tube containing the measuring device. During the process of measurement of a liquid volume using the measuring device disclosed herein, the decanting of the supernatant is preferably achieved by substantially inverting the laboratory tube and removal of the supernatant thereby.

Once the desired volume of liquid is retained by the measuring device in the base of the cooperating laboratory tube, then all or part of that volume of liquid or suspension may be removed. Preferably, the liquid or suspension is removed by its withdrawal by a pipe inserted into the passage of the measuring device. In this context, inserting a pipe into the passage is done for the purposes of achieving removal of the liquid from the volume retained in the laboratory tube beneath the measuring device. Accordingly, in this context, inserting the pipe into the passage also encompasses the option of inserting the pipe through the passage. Withdrawal of the liquid via the pipe can be achieved by a number of standard means. Preferably, this is by means of generation of a partial vacuum by the operation of a piston or suction developed by the reinflation of a pipette bulb. Accordingly, the pipe may be a pipette tip or hollow (e.g. hypodermic) needle. Preferably, the pipe is a pipette tip.

The invention will now be described with reference to the following drawings and examples in which:

Fig.1 A shows a side view of an insert for a laboratory tube. Fig. 1 B shows a top view of the insert shown in Fig.1 A. Fig.1 C shows a cross-sectional view of the insert shown in figures 1A and 1 B along section A-A, as shown in Fig.1 A.

Fig.2 and its constituent diagrams Fig.2A, B and C are identical to those shown in Fig.1 A but shows specific dimensions of the insert in millimetres.

Fig.3A shows a side view of an alternative insert for laboratory or centrifuge tubes. Fig.3B shows a top view of the insert shown in Fig.3A. Fig.3C shows a cross-section along Section A-A, as illustrated in Fig.3A. Fig.4 and its constituent diagrams Fig.4A, B and C are identical to those shown in Fig.3 but also show the dimensions of the laboratory tube insert in millimetres by way of serving as a specific example.

Fig.5A shows a side view of an alternative insert for laboratory or centrifuge tubes. Fig.5B shows a top view of the insert shown in Fig.5A. Fig.5C shows a cross-section along Section A-A, as illustrated in Fig.5A.

Fig.6 and its constituent diagrams Fig.6A, B and C are identical to those shown in Fig.5 but also show the dimensions of the laboratory tube insert in millimetres by way of serving as a specific example.

Example 1

In order to measure a specific volume within a centrifuge tube, in this case 300 microlitres (pl), an insert of the invention is placed in the laboratory tube such that the outer surface of the insert abuts the inner walls of the laboratory tube in order to provide a flush fit against the walls. That is, gravity can be used to pull the insert into place against the walls of the centrifuge tube while the final position of the insert is at a predetermined distance above the base of the tube.

The insert is substantially annular with an outer surface that substantially matches the dimensions of the inner wall of the laboratory tube. An example of such an insert apparatus is shown in Figs. 3A and 3B. In this instance, the insert has outer dimensions to match the dimensions of the inner walls of a 15 mm Falcon® laboratory tube in order that the insert will rest in the tube at the desired position above the base of the tube.

The insert also has a passage that is coaxial with the circular cross-section of the laboratory tube. In this case, the aperture tapers from 8.5mm at the proximal end of the insert (which is closer to the mouth of the laboratory tube) to 5mm at the distal end of the insert (which is closer to the base/bottom of the laboratory tube). The contour of the tapered aperture is shown in Figs.3B and 3C. The insert sits within the laboratory tube and the liquid to be processed is then also introduced to the laboratory tube. Typically this is an animal or human urine sample. However, any suitable liquid or suspension may be processed in concert with the present invention.

Following introduction of the liquid to the laboratory tube, the insert is then firmly seated in place either by external pressure or, preferably, by centrifugation.

Following fixing the insert in position, preferably by centrifugation, the tube is removed from the centrifuge and the supernatant decanted. The specific volume to be measured (in this case 300 microlitres) is retained at the distal end of the tube beneath the insert, i.e. between the lower surface of the insert and the base of the tube. While the passage through the insert is open, surface tension causes the liquid to be retained by the insert. Furthermore, the amount of liquid retained is controlled by the dimensions of the insert and the volume of the reservoir defined beneath the insert and by the walls of the laboratory tube. Thus a defined and accurately measured volume of liquid is retained in the centrifuge tube following decanting the supernatant.

The retained liquid volume can then be simply removed by way of a standard pipette and then used for further testing or processing.

Example 2

The insert is substantially annular with an outer surface that substantially matches the dimensions of the inner wall of the laboratory tube. An example of such an insert apparatus is shown in Figs. 1A and 1 B. In this instance, the insert has outer dimensions to match the dimensions of the inner walls of a 15 mm Falcon® laboratory tube in order that the insert will rest in the tube at the desired position above the base of the tube.

The insert also has a passage that is coaxial with the circular cross-section of the laboratory tube. In this case, the aperture is contoured internally to provide a funnel, whose upper bowl portion narrows to a central cylindrical pipe that emerges at the lower surface of the insert. Such an insert is shown in Figs 1 A, 1 B and 1 C.

The insert sits within the laboratory tube and the liquid to be processed is then also introduced to the laboratory tube. Typically this is an animal or human urine sample. However, any suitable liquid or suspension may be processed in concert with the present invention.

Example 3

The insert is substantially annular with an outer surface that substantially matches the dimensions of the inner wall of the laboratory tube. An example of such an insert apparatus is shown in Figs. 5A and 5B. In this instance, the insert has outer dimensions to match the dimensions of the inner walls of a 15 mm Falcon® laboratory tube in order that the insert will rest in the tube at the desired position above the base of the tube.

The insert also has a passage that is coaxial with the circular cross-section of the laboratory tube. In this case, the aperture is contoured internally to provide a funnel, whose upper, tapered bowl portion narrows to a central cylindrical pipe that emerges at the lower surface of the insert. Such an insert is shown in Figs 5A and 5B.

In this case, the aperture tapers from 12.6mm at the proximal end of the funnel portion (which is closer to the mouth of the laboratory tube) to 5mm at the distal end of the insert (which is closer to the base/bottom of the laboratory tube) with the tapered section of the funnel being 9.4mm in height. The funnel section directs flow into a 5mm diameter pipe section of 7mm in length. The contour of the tapered aperture is shown in Figs.6B and 6C.

Thus the invention provides a measuring device for operation with a compatible laboratory tube, preferably a centrifuge tube, whereby a defined volume of liquid is retained beneath the measuring device in the laboratory tube upon in version of the laboratory tube to decant the supernatant. Accordingly, methods of measurement of liquid volumes using the measuring device and a cooperating laboratory tube are also provided. Furthermore, a system for manufacturing the measuring device comprising an injection moulding tool is also provided here by. These developments offer improvements to the convenience of measurement of defined liquid volumes and also improvements in the consistency and efficiency of measuring such volumes of liquid and/or suspension, especially in the context of biological samples, e.g. urine.

Claims

1 . A measuring device for insertion in a cooperating laboratory tube,

(a) wherein the device has a first, upper surface, a second, lower surface, and a circumferential edge, wherein the circumferential edge is shaped to substantially match a portion of the inner wall of the laboratory tube,

(b) wherein the device, when installed in the laboratory tube, seats in a predetermined position in spaced separation from the bottom of the tube at a pre-determined distance therefrom,

(c) and wherein the first and second surfaces are linked by a passage through the device from the upper surface to the lower surface.

2. A measuring device according to claim 1 , wherein the passage is open.

3. A measuring device according to claim 1 , wherein the upper surface is substantially perpendicular to the longitudinal axis of the laboratory tube.

4. A measuring device according to any preceding claim, wherein the measuring device seats with a plug fit in the cooperating laboratory tube.

5. A measuring device according to any preceding claim, wherein the space encompassed by the lower surface of the measuring device and the walls of the cooperating laboratory tube has a volume of 5ml, 4 ml, 3 ml, 2.5 ml, 2 ml, 1 .5 ml, 1 ml, 500 pl, 300 pl, 200 pl, 100 pl, or 50 pl; preferably, the volume of the reservoir is 300 pl.

6. A measuring device according to any preceding claim, wherein the device is made of plastics material, preferably the plastics material is biologically inert.

7. A measuring device according to any preceding claim, wherein the cooperating laboratory tube is a centrifuge tube.

8. A measuring device according to any preceding claim, wherein the cooperating laboratory tube is a 50 ml tube, 15 ml tube, 5 ml tube, 2 ml tube, 1.5 ml tube, or 1 ml tube.

9. A measuring device according to any preceding claim, wherein, passage has walls that taper inwards from the upper face to the lower face

10. A measuring device according to any preceding claim, wherein the passage is parallel with the central axis of rotation of the centrifuge tube.

11 . A method of measuring a volume of liquid comprising the steps of:

(a) seating a measuring device according to any of claims 1 to 10 in a cooperating laboratory tube to define a reservoir between the base of the laboratory tube and the lower surface of the measuring device;

(b) introducing an amount liquid or suspension to the laboratory tube such that the reservoir is filled with liquid or suspension; and

(c) decanting the liquid retained above the upper surface of the measuring device from the laboratory tube, while retaining the liquid or suspension filling the reservoir, wherein the measuring device seats in position, and thus substantially seals the tube, apart from the passage connecting the upper and lower surfaces of the measuring device.

12. A method of measuring a volume of liquid according to claim 11 , wherein the seating step is achieved via axial force on the measuring device towards the base of the cooperating laboratory tube, preferably the axial force is provided by centrifugation.

13. A method of measuring a volume of liquid according to claim 11 or claim 12, wherein the decanting is achieved by substantially inverting the laboratory tube.

14. A method according to any of claims 11 to 13, wherein the method further comprises removal of all or a part of the liquid or suspension retained in the reservoir.

15. A system comprising an injection moulding tool for manufacturing a device of any of claims 1 to 10.