Sampling Device
20230264190 · 2023-08-24
Inventors
Cpc classification
B01L3/502707
PERFORMING OPERATIONS; TRANSPORTING
B01L3/5055
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/069
PERFORMING OPERATIONS; TRANSPORTING
B01L3/5023
PERFORMING OPERATIONS; TRANSPORTING
International classification
Abstract
A device for use in the separation of biological samples into a solid component and a liquid component. The device comprises a front cover and a back cover connected at a hinge portion such that the device is operable between an open position and a closed position. A separation membrane is arranged to retain the solid component and to allow the liquid component to pass therethrough, and an absorption membrane is arranged to retain the liquid component. The separation and absorption membranes are arranged in a layered structure between the front and back covers. Opening the device from the closed position to the open position causes the separation and absorption membranes to bend, thereby applying a compressive force to the membranes.
Claims
1. A device for use in the separation of biological samples into a solid component and a liquid component, the device comprising: a front cover and a back cover connected at a hinge portion such that said device is operable between an open position and a closed position; (ii) a separation membrane arranged to retain the solid component and to allow the liquid component to pass therethrough; and (iii) an absorption membrane arranged to retain the liquid component; wherein said separation and absorption membranes are arranged in a layered structure between the front and back covers; and wherein opening the device from the closed position to the open position causes said separation and absorption membranes to bend thereby applying a compressive force to said membranes.
2. The device as claimed in claim 1, wherein the separation membrane comprises a first fixed end and a first free end, and the absorption membrane comprises a second fixed end and a second free end, wherein the first and second fixed ends are both fixed to the front cover or the back cover at, or close to, the hinge portion of the device, and the first and second free ends are fixed together and are free to move laterally with respect to the first and second fixed ends as the device moves between the open and closed positions.
3. (canceled)
4. The device as claimed in claim 2, wherein the separation membrane and absorption membrane are fixed by an elongate anchor that extends substantially across the width of the device.
5. The device as claimed in claim 1, wherein the device further comprises a straining portion.
6. The device as claimed in claim 5, wherein the opening of the device causes the straining portion to apply the compressive force to said separation and absorption membranes.
7. The device as claimed in claim 1, wherein the separation membrane is arranged above the absorption membrane.
8. The device as claimed in claim 1, wherein the separation membrane and absorption membrane can be separately retrieved by punching out said membranes.
9. The device as claimed in claim 1, wherein the front cover and/or the back cover are made from a ‘hole-punchable’ material.
10. The device as claimed in claim 1, wherein the biological sample is at least one of: blood, cerebrospinal fluid, urine, saliva, tear fluid, lymphatic fluid, tissue fluid, bronchi-alveolar lavage (BAL), and ascites.
11. The device as claimed in claim 1, wherein the separation of biological samples into a solid component and a liquid component occurs by capillary action.
12. The device as claimed in claim 1, wherein the separation membrane comprises a filter paper that filters the liquid component of the biological sample, while capturing the solid components.
13. The device as claimed in claim 1, wherein the separation membrane layer comprises a single separation membrane or a plurality of separation membranes.
14. The device as claimed in claim 1, wherein the absorption membrane comprises an absorptive paper that captures the liquid component of the biological sample.
15. The device as claimed in claim 1, wherein the separation membrane or plurality of separation membranes are impregnated with active agents.
16. The device as claimed in claim 1, wherein the solid component comprises a cellular component.
17. A method of separating biological samples into a solid component and liquid component using the device of claim 1, the method comprising: opening the device; (ii) providing a sample from a subject; (iii) applying said sample to the layered structure; (iv) allowing the biological sample to substantially dry; and (v) closing the device.
18. The method as claimed in claim 17, wherein the sample is provided by a non-invasive means.
19. The method as claimed in claim 17, wherein after step (iv) a separating leaflet is provided to interleave the separation membrane and absorption membrane.
20. The method as claimed in claim 17, wherein the solid component and liquid components are removed after step (v) by punching the sample out of the device.
21. The method as claimed in claim 17, wherein after the step (v) the device can be readily stored and stacked for transportation.
22. A device for use in the separation of biological samples into a solid component and a liquid component, the device comprising: a front cover and a back cover connected at a hinge portion such that said device is operable between an open position and a closed position; (ii) a separation membrane arranged to retain the solid component and to allow the liquid component to pass therethrough; (iii) an absorption membrane arranged to retain the liquid component; and (iv) a manually-operable actuation member; wherein said separation and absorption membranes are arranged in a layered structure between the front and back covers; and wherein the manually-operable actuation member is arranged such that, when operated, the actuation member causes said separation and absorption membranes to bend thereby applying a compressive force to said membranes.
23. The device as claimed in claim 22, wherein the manually-operable actuation member comprises a pull cord, wherein pulling of the pull cord causes said separation and absorption membranes to bend thereby applying the compressive force to said membranes.
24. (canceled)
25. (canceled)
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0093] Certain embodiments of the present invention will now be described with reference to the accompanying drawings, in which:
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DETAILED DESCRIPTION
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[0107] Specifically,
[0108] As can be clearly seen from
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[0110] The straining portion also has free ends 13, which may be attached to the free ends 8 of the separation and absorption membranes 6, 7 by, for example, an adhesive or by a staple, as described below with reference to
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[0113] As shown in
[0114] Thus, upon opening the device, the free ends of the straining portion 13 slide along the back cover 2 thereby pulling the free ends 8 of the membranes 6,7 closer to the hinge portion 11 of the device 100. This pulling of the free ends 8 of membranes 6,7 by 13 serves to bend the two membranes 6,7. This forces membrane 6,7 into close contact and compresses membranes 6,7 such that they become held together tightly. A relatively uniform pressure is therefore imparted on membranes 6,7 when the device 100 is opened as a compressive force is applied to the membranes 6,7. This serves to ensure efficient wicking of liquids from biological samples deposited on separating membrane 6 onto the absorbing membrane 7. It can be clearly seen from the accompanying drawings how the separation membrane 6 and absorption membrane 7 become tightly pressed against one another as they bend.
[0115] When the device 100 is in the open configuration as shown in
[0116] The liquid component of the biological sample, i.e. the blood plasma in this example, will be drawn through the separation membrane 6 and will collect on the absorption membrane 7. This may be driven by capillary action, whereby the absorption of the liquid component onto the absorption membrane 7 serves to drive the flow of the liquid component through the separation membrane 6. In order to obtain effective separation of the biological sample, it is advantageous to provide a uniform pressure applied across the layered separation membrane 6 and absorption membrane 7. The bending of the separation membrane 6 and absorption membrane 7 as depicted in
[0117] It will be appreciated that the opening of the device bends the separation and absorption membranes 6, 7 in a manner similar to so-called ‘pop-up books’, insofar as the act of opening a book to a new pair of pages pulls on the paper fixed to said pages thereby causing the paper to rise out of the pages where they had previously been lying flat.
[0118] Once the biological sample is applied to the apex of the layered structure formed from the separation membrane 6 and absorption membrane 7, the sample should be given sufficient time to become separated into the cellular component and subsequently substantially dry before the device 100 is returned to the closed position as shown in
[0119] Separating and drying biological samples on separate membranes 6, 7 is an attractive approach to collect and maintain samples. This can serve to stabilise samples by, for example, reducing enzymatic activity in the dried state, either for short- or long-term storage, thereby simplifying the standardisation of sampling. The act of drying may also serve to remove well-known variables leading to inconsistent processing, for example, due to haemolysis or other forms of cell death, nucleic acid or protein degradation, or other changes, e.g. post-translational modifications of proteins. The material obtained from, for example, single drops of dried blood suffices for many different types of analyses. Several small aliquots of the same dried blood sample may be utilised for analysis of, for example, nucleic acids, proteins or metabolites, etc.
[0120] Upon closing the device 100, the free ends 8 of the membranes 6, 7 will move away from the separation and absorption membrane fixation 9 and the straining portion fixation 3. As such, the separation membrane 6 and absorption membrane 7 will no longer be compressed and will resume a flat position; thereby allowing the front cover 1 and back cover 2 to close over the separation membrane 6, absorption membrane 7 and straining portion 5.
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[0122] As outlined above, the separation membrane 6 and the absorption membrane 7 are arranged in a stacked or layered structure. The biological sample which may be, for example, blood is applied to the separation membrane 6. In the particular embodiment depicted in
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[0124] In this particular experimental set-up, the Vivid grade was used as the filter paper for the separation membrane 6, and the Whatman Grade 1 paper was used as the absorption membrane 7. In this particular embodiment, the membranes 6, 7 are 5 cm long when laid flat, i.e. when the membranes 6, 7 are not subject to any kind of bending.
[0125] When applying the various curvatures shown in
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[0128] As outlined previously, the pulling of the free ends 8 of the membranes 6, 7 towards the fixed ends 9 of the membranes 6, 7 and straining portion fixation 3 allows the stiff straining portion 5 to exert a force on the separation membrane 6 and absorption membrane 7. This forces the separation membrane 6 and absorption membrane 7 to bend and compresses these membranes 6, 7 such that they become tightly held together. In this particular embodiment, the straining distance as shown in
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[0130] These QR codes 15 are useful in identifying which sample came from which subject when the devices 100 are collected, e.g. by a biobank. When the devices 100 outlined above are supplied to subjects, for example human patients, a user can scan the QR code 15 using an external device to associate the biological sample with the subject, where this ‘external device’ may be a device such as a smartphone or tablet that has a camera suitable for scanning the QR code 15 in a means known in the art per se. In another example, separate QR codes or other identifiers could be applied to the two membranes to ensure that the source of aliquots retrieved from the membranes, e.g. cells or plasma, can be correctly identified. Though, it will be appreciated that separate QR codes or other identifiers may be applied anywhere on the device.
[0131] For example, the device may run an application (or ‘app’) where the details of the subject are captured. Specifically, in this embodiment, the user must supply log in credentials, i.e. the user (which may be the subject themselves or another person assisting the sampling of the subject such as a friend, family member, carer, nurse, doctor, clinician etc.) must log in to the app using a username and password that uniquely identifies them or the subject. The user credentials may be verified, e.g. locally or via a remote server, and result in the proper selection of the correct user identifier relating to the subject or user.
[0132] Once logged into the app, the QR code or codes 15 can be scanned, ‘tying’ a device identifier associated with the device 100 to the user identifier associated with the subject or user, and the user identifier and device identifier can be stored together as a linked pair in a database, either locally or remotely as appropriate, such that samples collected on the device 100 as outlined above are properly attributed to the correct subject. Generally, the linked pair of user identifier and device identifier will be transmitted to a remote server that contains the database, for example to a biobank that collects the devices 100.
[0133] At the biobank itself, the QR code or codes 15 may be scanned in order to determine the user identifier and device identifier, such that measurements and conclusions relating to the cellular and liquid components of the biological sample can be stored in a database in relation to the correct subject.
[0134] Sample identifiers may be provided in addition to, or instead of, the device identifier. These sample identifiers may relate to the specific solid and liquid samples (i.e. correspond to the membranes 6, 7 themselves), and these identifiers may be stored in the database, linked to the correct user identifier.
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[0136] The transition of the device 100 from the closed position to the open position can be understood by reference to
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[0138] In particular, the manually-operable actuation member of the device 200 comprises a pull cord 18. Pulling of the pull cord 18 in the direction shown by arrow 19 causes said separation and absorption membranes 6,7 to bend thereby applying the further compressive force to said membranes.
[0139] In this particular embodiment, the straining portion 10″ This pull cord 18 arrangement can be combined with any of the approaches outlined above in which the membranes are anchored to a cover of the device can be combined, such that opening the device applies a first compressive force on the membranes, and pulling the pull cord applies an additional compressive force on the membranes.
[0140] The device in accordance with embodiments of the present invention may readily provide suitable separation and collection of a biological sample obtained by, for example, finger pricks. The cellular fraction and liquid fraction can be readily split into aliquots to be processed in a clinical chemistry laboratory, subject to approval by donors. This would enable diagnostic tests to be carried out on samples, for medical and wellness purposes, and would permit the collection, transportation, build-up and long-term storage of vast biobanks at little cost, enabling easy follow-up by reference to earlier samples. Similar biological sample collections will also be of value in, for example, veterinary medicine.
[0141] The device of the present invention will be of interest for, e.g., prospective sample collection, as well as for disease-, therapy- or wellness-related collections. The device as described herein permits samples to be affordably collected from very large numbers of donors with potentially many samples being harvested from each individual. As described above, there is an increased interest by individuals in supplying biological samples, for example blood, and having these tested for wellness purposes. There is an increasing demand for individuals to have their biological samples analysed with respect to, for example, overall health checks and nutritional status, (auto)immunity states, signs of infection, etc. The device of the present invention offers a user-friendly means by which a wellness-conscious individual can simply prick their finger and send a sample via regular mail for analysis. Such a device also offers patients undergoing treatment the opportunity to take regular follow-up samples in their own homes and send these for analysis. Furthermore, sample donors taking part in e.g. research projects or clinical trials can be monitored by biological samples being taken by the individuals in their homes. It can also be readily appreciated that both prospective and disease-specific biobanks could be collected and maintained a low cost using the device described herein. The device of the present invention with the collected material may also be readily stored in large quantities, whether storage is, for example, at room temperature or in freezers.
[0142] The device of the present invention may also serve to allow detection and analysis of genetic material, e.g. DNA or RNA, in both the cellular and liquid fractions of the biological sample. It is well-known in the art per se that genetic material can be analysed in dried biological samples. In the case of blood samples, even after perfect separation of the liquid and cellular components, there will be DNA or RNA that is found in the cellular fraction and cell-free DNA or RNA present in the liquid fraction. By separating and collecting dried cellular and liquid fractions, the device of the present invention provides an effective means of analysing both cell-based DNA and cell-free DNA, as well as cell-based RNA and cell-free RNA
[0143] The availability of collection devices, such as the device described herein, that serve to preserve the cellular component and liquid component of a biological sample may motivate the application of current and development of new molecular analysis assays of biological samples. Examples of suitable molecular analyses of the collected biological sample, for example blood, will be well-known to those skilled in the art. For example, the numbers of cells from different hemopoietic lineages, including subsets such as the different forms of T cells, which may be estimated by measuring levels of characteristic transcripts or proteins collected from the blood sample. It will be readily appreciated by those skilled in the art that several suitable techniques for protein measurements are available, such as proximity ligation assays or multiplex proximity extension assays, enzyme-linked immunosorbent assay (ELISA) (e.g. direct, sandwich, competitive or reverse ELISAs), or mass spectrometry, etc. In the case of nucleic acid analysis, different forms of polymerase chain reaction (PCR) or related amplification methods such as real-time PCR, reverse transcriptase PCR, digital PCR or loop-mediated isothermal amplification (LAMP) or nucleic acid sequence-based amplification (NASBA) assays, etc. could be utilised, as could e.g. padlock probe ligation assays. It may also be of interest to develop assays for metabolites or other analytes by, e.g., mass spectrometry.
[0144] Thus it will be appreciated that embodiments of the present invention provide a device that enhances the separation of cellular and liquid components of a biological sample in a small, light-weight, cheap, and easily-disposable package that is highly suitable for both storage and transportation. As outlined above, this device may have a ‘book-like’ structure of the present device, which may make it easy to stack multiple such devices in a way analogous to books on a bookshelf.
[0145] While specific embodiments of the invention have been described in detail, it will be appreciated by those skilled in the art that the embodiments described in detail are not limiting on the scope of the invention.