GB2537637A

GB2537637A - Improved cap strips

Info

Publication number: GB2537637A
Application number: GB1506784.6A
Authority: GB
Inventors: Francis Day Paul
Original assignee: 4Titude Ltd
Current assignee: 4Titude Ltd
Priority date: 2015-04-21
Filing date: 2015-04-21
Publication date: 2016-10-26
Also published as: GB201506784D0

Abstract

A cap strip body suitable for sealing a plurality of tubes arranged in an elongated spaced apart linear arrangement, the cap strip body comprising a plurality of tube caps 35, 36, 37 integrally connected in a corresponding elongated spaced apart linear arrangement and arranged symmetrically about a longitudinal axis, wherein adjacent tube caps are connected by a single substantially flexible tether 31, 32, 33, such that adjacent tube caps may move backwards and forwards with respect to one another along the longitudinal axis of the strip, whilst remaining tethered together. The tether may have a curved or rectilinear configuration. The tether may cross the longitudinal axis (fig 4, 5). Alternatively, the tether may not pass through the longitudinal axis with adjacent tethers arranged on alternative sides of the axis. The tethers have a sinusoidal profile or a undulating profile. Preferably the cap strip body is formed from an optically transparent plastics material such as a polycarbonate.

Description

Improved Cap Strips

Field of the Invention

The present invention relates to cap strips for sealing a strip or row of tubes or vials.

It is particularly applicable to cap strips for sealing a strip of PCR tubes and especially tubes where the contents emit a fluorescence signal.

Background to the Invention

Cap strips which are designed to ensure an effective seal in a row of tubes arranged in a 96 well format are known. Examples of such known tubes are shown in Figures 1 and 2. However, these known tubes suffer from a number of disadvantages. Firstly, although tubes produced in a 96 well format or array are usually precision moulded, the mouldings from different manufacturers may vary very slightly one form another. Furthermore, once subjected to repeated PCT thermal cycling the distance between tube centres may change slightly. In addition, tubes can be made from a variety of different plastics that expand and contract in different ways and by different amounts both during the moulding process and during use. As a result, one particular design and manufacture of cap strip does not always align with and fit exactly onto the entire length of a corresponding row of tubes in an array.

Secondly, most cap strips and tubes are formed from polypropylene. Whilst polypropylene has many advantages, it is not as optically clear as some other polymers in relation to light given off by common qPCR fluorophores. However, if conventional cap strip designs and moulding tools are used with plastics materials having greater optical clarity, such as polycarbonates, the resultant cap strips, whilst more being more optically transparent, may have a cap pitch which is outside the normal manufacturing tolerance. As a result of this misalignment it can be very difficult for an operator to insert all of the caps in a strip onto a complete row of tubes without damaging one or more caps.

It is therefore an object of this present invention to overcome or mitigate some or all of the problems outlined above.

Summary of the Invention

According to a first aspect of the present invention there is provided a cap strip body according to Claim 1. For example there is provided a cap strip body suitable for sealing a plurality of tubes arranged in an elongated spaced apart linear arrangement, or row, said cap strip body comprising a plurality of tube caps integrally connected in a corresponding elongated spaced apart linear arrangement and arranged symmetrically about a longitudinal axis, wherein adjacent tube caps are connected by a single substantially flexible tether, such that adjacent tube caps may move backwards and forwards with respect to one another along the longitudinal axis of the strip, whilst remaining tethered together.

This provides a flexible tether or inter cap connector arrangement with the flexibility to accommodate any misalignment between the pitch of the caps and the pitch of the tube in their respective arrays, making it much easier for an operator to insert the caps into the tubes without damage. In this context the terms "tether' and "inter cap connector" are intended to have the same meaning and the terms may be used interchangeably.

Preferably the tether is substantially curvilinear in configuration. A curvilinear, rather than a straight inter cap connector is a simple way of connecting adjacent caps whilst providing freedom for adjacent caps to move along the longitudinal axis with respect to each other to accommodate any misalignment.

In an alternative preferred embodiment the tether is substantially rectilinear in configuration. In this context the term "rectilinear" is considered as a subset of, and fall within the definition of, "curvilinear'. It will be understood that a tether with the necessary flexible properties can be formed from a series or plurality of straight sections of tether joined end to end, rather than being in the form of a smooth continuous curve.

Preferably the tether passes across or through the longitudinal axis as it joins adjacent tube caps. By creating a tether with a relatively long path between adjacent tubes the resultant tether achieves additional flexibility.

Preferably adjacent tube caps are joined in a substantially head to tail arrangement.

In one such arrangement the points at which the tethers are attached are substantially diagonally opposite each other on a particular cap and therefore on opposite sides of the longitudinal axis. By repeating this arrangement on adjacent caps an undulating pattern of tethers is produced.

In a further preferred embodiment adjacent tube caps are joined in a substantially head to tail/tail to head arrangement. In this arrangement the points at which the tethers are attached to a particular cap are substantially opposite each other but on the same side of the longitudinal axis of the cap strip. By repeating this arrangement on adjacent caps and having each tether pass across or through the longitudinal axis of the cap strip as it joins the adjacent tube cap a substantially sinusoidal formation of tethers or inter cap connectors is created.

Preferably the arrangement of tethers on adjacent caps of the cap strip body follows a substantially undulating configuration.

In an alternative preferred embodiment the arrangement of tethers along the cap strip body follows a substantially sinusoidal configuration.

In one preferred embodiment adjacent tube caps are joined by a tether without that tether passing across or through the longitudinal axis as it joins adjacent tube caps.

In a further preferred embodiment adjacent tube caps are joined by tethers that are arranged on alternate sides of the longitudinal axis.

Preferably the cap strip body is formed from a plastics material such that the centre of each tube cap is substantially transparent to visible light and preferably the centre of each tube cap transmits more than 85% of any visible light emitted in a tube.

Preferably the centre of each tube cap transmits more than 85% of light having a 30 wavelength between 450nm and 700nm emitted in a tube and more preferably the centre of each tube cap transmits more than 85% of any light having a wavelength of substantially 520nm emitted in a tube.

Preferably the cap strip body is formed from a polycarbonate, a particularly preferred polycarbonate being PANLITE(RTM). However, other suitable substantially transparent polycarbonates can be used, as can other optically transparent polymers that can be injection moulded. It will be understood that the present invention includes the use of known and yet to be discovered optically clear polymers including polycarbonates and also Cyclic Olefin Copolymers (COC) such as TOPAS.

Brief Description of the Drawings

The present invention will now be described by way of example only with reference to the accompanying drawings in which:-Figures 1 & 2 illustrate examples of Prior Art cap strips; Figures 3, 4 & 5 illustrate top, side, bottom and perspective views of three embodiments of the invention; Figure 6 shows a table of results from a series of experiments to determine the percentage loss of fluorescent light emitted in tubes sealed with different types of caps.

Description of the Preferred Embodiments

Figure 1 shows a typical prior art cap strip body for capping a row of 8 tubes or vials. A common arrangement of tubes or vials used in life science laboratories is an 8 x 12 array of 96 vials. These can be sealed when required using strips of 8 caps or strips of 12 caps. These cap strips are usually applied by hand by an operator. In the cap strip shown in Figure 1, each cap 15, 16, 17 etc is attached to at least one adjacent cap by two tethers or inter cap connectors 11, 12 and 13, 14. This double tether arrangement holds each cap firmly in position at a fixed pitch in relation to the adjacent cap(s). The same arrangement would apply in the case of a 12 cap strip, which is also the case in the various examples described below.

The arrangement shown in Figure 2 comprises a strip of 8 caps, 25, 26, 27 etc wherein each cap is attached to at least one adjacent cap by just one straight tether 21, 22, 23, 24 aligned substantially along the longitudinal axis 'A' of the cap strip body. Once again this tether arrangement holds each cap firmly in position along the line of the longitudinal axis in relation to adjacent cap(s) such that the cap pitch is again substantially fixed. This is because a straight tether made from polypropylene, for example, is substantially incompressible along the plane of its longitudinal axis, although it has the capacity to flex out of that plane.

Figure 3 shows a first embodiment of the present invention. This shows a strip 30 of 8 tube caps 35, 36, 37 etc each connected by a single curvilinear tether 31, 32, 33, 34. Whilst these tethers are shown as smooth curves it will be appreciated that they could take the form of two (or more) substantially straight sections connected together in the shape of a A. This could be described as a rectilinear form of configuration and would give a similar degree of "flex" to the curvilinear shape shown in Figure 3.

Where a cap is attached to another cap on each side, i.e. the particular cap is not at one end of the strip, the two tether points are substantially diagonally or diametrically opposed to each other across the top of the cap. This leads to a substantially sinusoidal configuration of tethers. To achieve this sinusoidal configuration no tether needs to cross the longitudinal axis 'A-A' of the cap strip in this particular embodiment.

It is also possible that all of the tethers of the embodiment shown in Figure 3 could be located on the same side of the longitudinal axis of the cap strip body (not shown) in which case the sinusoidal configuration of tethers would no longer be present. This altemative arrangement would work perfectly well, but is not so aesthetically pleasing.

An important feature of the present invention therefore is a single tether or inter cap connector between adjacent caps, formed from a thin strip or ribbon of the same material from which each cap is formed. This new tether design easily accommodates variations in tube/cap pitches and allows the cap strip to be applied more easily. Although this may seem a minor point, in practise it is actually very useful as with the standard cap strips currently on the market the operator has to start applying the caps in the middle of a row and insert the caps outwards in both directions. If this is not done, and the operator just starts from one end of the strip, when one gets to the other end unless the pitch of the tubes matches exactly the pitch of the caps the operator ends up snagging the cap sealing area of the last cap which often leads to at least the end tube leaking.

So by designing the tethers/inter cap connectors in a different way to existing caps it is possible to accommodate some variation in the well to well pitch of the tubes that the caps are intended to seal, as well as cap to cap pitch variations.

It can also be seen from Figure 3, and from the other Figures, that the top of each cap 38, 39 is substantially flat or planar on both the inside and the outside of the tube cap. This allows for the maximum transmission of light, as allowed for or that may be achieved according to the optical qualities of the plastics material used to make the cap strip (see below).

Figure 4 shows a second embodiment of the present invention. This shows a strip 40 of 8 tube caps 45, 46, 47 etc each connected by a single curvilinear tether or inter cap connector 41, 42, 43, 44. In this embodiment the bottom right hand corner of one cap is connected to the top left hand corner of the adjacent cap when viewed in the orientation shown in Figure 4 and going from left to right along the longitudinal axis 'A-A'. This provides a substantially undulating configuration of tethers. It will be understood that each cap is substantially circular and does not have true corners as such. However, in this context where the caps are arranged in a linear strip, the point at which a tether meets a cap creates what is referred to here as a 'corner'.

As in the embodiment described above the tethers are shown as smooth curves. But this need not necessarily be the case. The tethers could take the form of a series of substantially straight sections connected in the form of a Z (not shown).

This could be described as a rectilinear form or configuration of tether and would give a similar degree of "flex" to the curvilinear shape shown in Figure 4. In this disclosure, "rectilinear" is considered and defined as a sub-set of the term "curvilinear".

It will be appreciated that in this embodiment the tethers cross the longitudinal axis 'A-A' and have a substantially undulating configuration. The result of the shape and configuration of the tethers in this preferred embodiment is that there is a good deal of movement possible between adjacent caps although they tend to automatically return to their "as manufactured" pitch. The movement could be described as the movement you would get from a pleated fabric or bellows arrangement.

Figure 5 shows a strip 50 of tube caps 55, 56, 57 etc each connected by a single curvilinear tether. This is a variation of the embodiment shown in Figure 4. In this example the bottom right hand corner of one cap is connected to the top left hand corner of the adjacent cap, followed by the top left hand corner of that cap being connected to the bottom right hand corner of the adjacent cap. This is when the cap strip body is viewed in the orientation shown in Figure 5 and going from left to right along longitudinal axis A-A'. This provides a substantially sinusoidal or 'snake like' configuration of tethers and offers all the advantages described in relation to the embodiment shown in Figure 4 and described above. Other variations of rectilinear tethers as described above are equally applicable to this embodiment.

It will be appreciated that one reason for the tether being designed in this "snake" like way is to provide the flexibility of cap pitch, i.e. so that the centre to centre position of each cap in a strip of industry standard 8 or 12 caps has a greater working tolerance associated with it than if the caps have a non flexible double connector or single straight across connector. The reason this is beneficial is that the tube strips or plates that are manufactured are all meant to be on a 9mm pitch (well to well position). However the pitch of the tubes and plates will not be exactly 9mm and there will inevitably be a manufacturing tolerance associated with this positioning which typically could be +/-0.1mm. Likewise the caps would be made to a similar tolerance of +/-0.1mm.

Hence, there is the possibility that if each tolerance was -0.1 for the tubes and + 0.1 for each cap you could end up with two components, a tube strip and a cap strip, that are both manufactured to an acceptable manufacturing tolerance but when you try for example to put an 8 strip cap onto an 8 strip tube array the end tubes and caps could be (7x0.1 + 7X0.1) = 1.4mm out of alignment. If each tether does not have the flexibility designed within it to accommodate this misalignment it will be very difficult to insert all the caps without damaging them. This becomes an even bigger problem when dealing with a strip of 12 caps, and also when using tubes and caps manufactured from different plastics materials.

Caps according to the present invention can be made from a wide variety of plastics materials as determined by the materials specialist. Since many tubes and vials are made from polypropylene, the caps can also be made from polypropylene if required. However, polycarbonates generally have better optical properties than polypropylene, and cap strips made from polycarbonate allow for improved light transmission improving assay sensitivity. However, it should be noted that polycarbonates as a material do not shrink as much as polypropylene at high temperatures. Therefore during the PCR process polycarbonate caps get tighter when fitted in polypropylene tubes, thus enhancing the sealing effect of the cap and preventing any significant sample loss. In contrast, polypropylene caps actually get looser, causing a greater chance of sample loss.

The table in Figure 6 shows experimental results for caps according to the present invention made from polypropylene and PANLITE (RTM), which is the trade name of a particular commercially available polycarbonate supplied by Teijin Kasei Europe B.V., The Netherlands.

Referring to Figure 6, the results listed in the first 3 rows of the Table report scans of wells which were empty and without caps. It is known from experiments that have been done that when you scan a well for a second time the fluorescence signal changes and so it is important to establish as a baseline what that change would be without caps and with no dye. As can be seen from the Table the change is a consistent reduction, ranging from 3.2 to 5.96% as a percentage of the original reading.

Fluorescein was then added to wells described in the next 6 rows. Fluorescein emits light at the FAM wavelength and the wells were scanned initially without caps. As there is now fluorescein present the emission levels are much higher than for an empty tube by approximately 10 fold. Either Panlite caps or polypropylene (PP) caps were then fitted onto to the wells, which were then re-scanned and the emissions with the appropriate caps in place was measured, recorded, and the difference in RFU (relative fluorescence units) created by the various caps was calculated. It can be seen from the data that the PANLITE polycarbonate (PC) caps change the reading significantly less than the polypropylene (PP) caps and it has therefore been demonstrated conclusively that the polypropylene caps absorb more of the emitted fluorescence from Fluorescein dye than polycarbonate caps, and that there is improved wavelength transmission through the PC caps. For researchers in this field this offers the important benefit of a more sensitive assay.

In summary, caps made from polycarbonate instead of polypropylene offer significant optical benefits in qPCR assays, and the new designs for cap strips described herein make it possible, for the first time, to manufacture 8 and 12 cap strips from polycarbonate that will fit easily onto tubes/wells arranged in a 96 well array, regardless of what plastics material the wells are made from.

Claims

CLAIMS1. A cap strip body suitable for sealing a plurality of tubes arranged in an elongated spaced apart linear arrangement, said cap strip body comprising a plurality of tube caps integrally connected in a corresponding elongated spaced apart linear arrangement and arranged symmetrically about a longitudinal axis, wherein adjacent tube caps are connected by a single substantially flexible tether, such that adjacent tube caps may move backwards and forwards with respect to one another along the longitudinal axis of the strip, whilst remaining tethered together.
A cap strip body according to Claim 1 wherein the tether is substantially curvilinear in configuration.
3. A cap strip body according to Claim 1 or Claim 2 wherein the tether is substantially rectilinear in configuration.
4. A cap strip body according to any preceding claim wherein the tether passes across or through the longitudinal axis as it joins adjacent tube caps.
A cap strip body according to any preceding claim wherein adjacent tube caps are joined in a substantially head to tail arrangement.
6. A cap strip body according to any of Claims 1 to 4 inclusive wherein adjacent tube caps are joined in a substantially head to tail/tail to head arrangement.
A cap strip body according to any preceding claim wherein the arrangement of tethers along the cap strip body follow a substantially undulating configuration.
8. A cap strip body according to any preceding claim wherein the arrangement of tethers along the cap strip body follow a substantially sinusoidal configuration.
A cap strip body according to any of Claims 1 to 3 inclusive wherein adjacent tube caps are joined without the tether passing across or through the longitudinal axis as it joins adjacent tube caps.
10. A cap strip body according to Claim 9 wherein adjacent tethers are arranged on alternate sides of the longitudinal axis.
11. A cap strip body according to any preceding claim wherein the cap strip body is formed from a plastics material such that the centre of each tube cap is substantially transparent to visible light.
12. A cap strip body according to Claim 11 wherein the centre of each tube cap transmits more than 85% of any visible light emitted in a tube.
13. A cap strip body according to Claim 12 wherein the centre of each tube cap transmits more than 85% of light having a wavelength between 450nm and 700nm emitted in a tube.
14. A cap strip body according to Claim 13 wherein the centre of each tube cap transmits more than 85% of light having a wavelength of substantially 520nm emitted in a tube.
15. A cap strip body according to any preceding claim formed from a polycarbonate.
16. A cap strip body according to Claim 15 formed from PANLITE(Fcm).
17. A cap strip body substantially as herein described with reference to and as illustrated in any combination of Figures 3 to 5 inclusive.