PROCESSING OF DRIED BLOOD SAMPLES ON LATERAL FLOW PAPER
20230165494 · 2023-06-01
Inventors
Cpc classification
A61B5/150755
HUMAN NECESSITIES
A61B5/150343
HUMAN NECESSITIES
A61B5/150305
HUMAN NECESSITIES
A61B5/150259
HUMAN NECESSITIES
A61B5/150786
HUMAN NECESSITIES
International classification
Abstract
A grinder (220) is provided for use in a method of processing a piece of lateral flow paper, comprising a grinder body (222) defining a grinder storage volume (226) with a top opening for accessing the grinder storage volume and one or more through holes (228) providing a fluid connection through the grinder body into the grinder storage volume, wherein the grinder body further comprises one or more grinding protrusions (229) at an outer surface of the grinder body. Furthermore, a sample container (200) is provided for storing a blood sample provided on a piece of lateral flow paper, comprising a sample container body with a base part, a cylindrical wall extending from the base part and defining a storage volume with an opening for accessing the storage volume, wherein the base part comprises one or more protrusions (209) extending into the storage volume.
Claims
1. A device for collecting a sample of blood, comprising: a paper holder arranged to hold a piece of lateral flow paper in a paper holder storage volume; and a paper cover body for covering at least part of the piece of lateral flow paper in a paper cover body storage volume, wherein the paper holder is releasably connected to the paper sample cover body such that in a connected state, the paper holder storage volume is provided adjacent to the paper cover body storage volume and in a disconnected state, the paper holder can be moved away from the paper cover body.
2. The device according to claim 1, further comprising a sample container holder which is connected to the paper sample cover body and arranged to hold a sample container.
3. The device according to claim 1, further comprising a cartridge with a cartridge body arranged for housing at least part of the paper cover body, and wherein the paper holder and the paper cover body in connected state can be moved at least partially into and out of the cartridge body between a transport state wherein at least part of the paper holder is covered by the cartridge body, and an open state wherein the at least part of the paper holder is exposed.
4. The device according to claim 2, further comprising a test tube as a sample container, which test tube is held in the sample container holder, and wherein the test tube comprises a top opening facing towards the paper holder.
5. The device according to claim 4, further comprising a cartridge with a cartridge body arranged for housing at least part of the paper cover body, and wherein the paper holder and the paper cover body in connected state can be moved at least partially into and out of the cartridge body between a transport state wherein at least part of the paper holder is covered by the cartridge body, and an open state wherein the at least part of the paper holder is exposed, wherein the cartridge body comprises a window, the test tube comprises a marking on an outside surface, and in the transport state, the window is aligned with at least part of the marking.
6. The device according to claim 4, further comprising a paper strip as a piece of lateral flow paper, which paper strip is at a proximal end held by the paper holder, and of which a distal end extends into the test tube in the connected state of the paper holder and the paper sample cover body.
7. A method of processing a sample of blood on a piece of lateral flow paper, comprising: disconnecting a paper holder from a paper cover body to expose part of a piece of lateral flow paper held by the paper holder; on the exposed part of the lateral flow paper, determining a transition area between a first area with blood cells and a second area substantially without blood cells; and cutting the piece of lateral flow paper based on the determined transition area to obtain a cut off piece of the lateral flow paper comprising separated blood serum.
8. The method according to claim 7, wherein the determining of the transition area is performed by an optical sensor unit arranged for receiving a reflected optical signal from the lateral flow paper.
9. The method according to claim 7, further comprising depositing the cut off piece of lateral flow paper in a sample container, and adding a buffer fluid to the lateral flow paper in the sample container.
10. The method according to claim 9, wherein the cut-off piece of lateral flow paper is deposited into the sample container by virtue of gravity.
11. The method according to claim 9, further comprising disconnecting the paper holder from a sample container holder holding the sample container.
12. The method according to claim 9, further comprising placing a grinder into the sample container after the cut-off piece of lateral flow paper and the buffer fluid are deposited into the sample container, and using the grinder for mixing the cut-off piece of lateral flow paper and the buffer fluid.
13. The method according to claim 12, further comprising retrieving at least part of the buffer fluid from the grinder after the step of using the grinder for mixing the cut-off piece of lateral flow paper and the buffer fluid.
14. A grinder for use in a method of processing a piece of lateral flow paper, comprising: a grinder body defining a grinder storage volume with a top opening for accessing the grinder storage volume; and one or more through holes providing a fluid connection through the grinder body into the grinder storage volume, wherein the grinder body further comprises one or more grinding protrusions at an outer surface of the grinder body, which one or more grinding protrusions face away from the grinder storage volume.
15. The grinder according to claim 14, wherein the grinder body comprises a base part and a cylindrical wall protruding from the base part, and wherein the one or more through holes are provided through the base part.
16. The grinder according to claim 14, wherein the one or more grinding protrusions are provided adjacent to the one or more through holes.
17. A sample container for storing a blood sample provided on a piece of lateral flow paper, comprising a sample container body with a base part, a cylindrical wall extending from the base part and defining a storage volume with an opening for accessing the storage volume, wherein the base part comprises one or more protrusions extending into the storage volume.
18. The sample container according to claim 17, wherein the one or more protrusions are at least partially spherical.
19. The sample container according to claim 17, further comprising a foot part extending from the base part away from the opening, which foot part defines a hollow chamber with a chamber opening on an opposite side of the sample container than the opening of the storage volume.
20. A kit of parts to form a sample container assembly, comprising: the grinder according to claim 14; and a sample container for storing a blood sample provided on a piece of lateral flow paper, comprising a sample container body with a base part, a cylindrical wall extending from the base part and defining a storage volume with an opening for accessing the storage volume, wherein the base part comprises one or more protrusions extending into the storage volume, wherein the sample container is arranged to receive at least part of the grinder body in the storage volume.
Description
BRIEF DESCRIPTION OF THE FIGURES
[0031] In the figures,
[0032]
[0033]
[0034]
[0035]
[0036]
[0037]
[0038]
[0039]
DETAILED DESCRIPTION OF THE FIGURES
[0040]
[0041] In particular, in the disconnected state as shown in
[0042] The paper holder 102 comprises a reception opening 108 providing a flow path to a proximal end of the paper strip 104. When a sample of liquid blood is provided to the proximal end of the paper strip 104, part of the blood sample may migrate through the paper strip 104 towards a distal end of the paper strip 104, in a direction indicated with arrow 110. The reception opening 108 may be provided by a through hole, cavity, and/or any other type of opening in the paper holder 102.
[0043] The reception opening 108 ends in a paper holder storage volume 167 of the paper holder 102. This paper holder storage volume 167 may be defined as a volume defined by the paper holder 102 in which lateral flow paper may be contained. The paper holder storage volume 167 is in
[0044] The paper holder 102 and the paper cover body 106 are preferably releasably connected in the sense that they may be separated without being damaged. The connection may be provided by means of hinges, snap-fit connections, press-fit connections, other or a combination thereof.
[0045] In a released or disconnected state, the paper holder 102 and the paper cover body 106 are moved away from another, separating the paper holder storage volume 167 from the paper cover body storage volume 169. With the paper strip 104 being fit in the paper holder storage volume 167 of the paper holder 102, a part of the paper strip 104 is exposed, which exposed part was provided in the paper cover body storage volume 169 in the connected state, as described above.
[0046] As an option, the device 100 further comprises a sample container holder 112 arranged to hold a test tube 202 as an example of a sample container. The test tube 202 comprises an opening 244 for receiving at least part of the paper strip 104 into a storage volume of the test tube 202. For example, the test tube 202 may be clamped by the sample container holder 112.
[0047] Preferably, the test tube 202 is releasably connected to the sample container holder 112 such that the test tube 202 may be disconnected without damaging the test tube 202. Damage to the test tube 202 may possibly result in an undesired contamination of an inside of the test tube 202 and/or content inside the test tube 202 may leak out.
[0048] In particular, the sample container holder 112 is arranged to hold the test tube 202 in an orientation wherein the opening 244 of the test tube 202 faces towards the paper holder 102, and thus, in use, towards the paper strip 104. As such, when the device 100 is in use oriented substantially vertical—i.e. substantially parallel to the gravity vector—with the opening 244 facing upwards, part of the paper strip 104 may drop into the test tube 202. This part of the paper strip 104 may be either released from the paper holder 102 or from another part of the paper strip 104 which may remain attached to the paper holder 102.
[0049] In the embodiment of
[0050] The paper cover body 106 as shown in
[0051] Since the slit 114 is optional, it will be appreciated that embodiments of the device 100 are envisioned with the slit 114. As an alternative to the slit 114, one or more openings may be provided to form the viewing window for viewing part of the paper strip 104. The one or more openings may be formed as through holes, may be formed by an at least partially transparent part, or as a combination thereof.
[0052] The paper cover body 106 may be connectable to the paper holder 102. For example, as shown in
[0053] Through the one or more openings 166, the one or more latches 165 may be accessible when the paper holder 102 is connected to the paper cover body 106. As such, a machine may be used to engage the one or more latches 165 through the one or more openings 166 to disconnect the paper holder 102 from the paper cover body 106.
[0054]
[0055] In
[0056] In
[0057] In the open state, the device 100 may be arranged to receive the blood sample on the paper strip 104 through the opening 108. After the blood sample is received, the paper holder 102 may be moved towards the cartridge 180 to put the device 100 in the transport state shown in
[0058] As an option, the cartridge body 182 may comprise a window 184, which when present provides a passage for light through the cartridge body 182. As such, a part of the sample container 202 held in the sample container 112 may be aligned with the window 184 when the device 100 is in the transport state and/or in the open state. This part of the sample container 202 may comprise a marker such as a barcode, QR code, text, any other type of marking, or any combination thereof.
[0059] When the sample container 202 comprises such a marker, which is located to align with the window 184, even in the transport state of the device 100 the sample container 202 may be identified.
[0060] Also in embodiments of the device 100 without the cartridge 180 or the window 184, having a marker on the sample container 202 may be advantageous. The marker may allow automatic identification of the sample container 202, for example by a computer device with a scanner arranged to scan the marker.
[0061] In particular with embodiments of the device 100 comprising a sample container 202 held in the sample container holder 106, which in turn may be connected to the paper holder 102, the same sample container 202 remains associated with the same piece of lateral flow paper held in the paper holder 102. It may be more convenient to provide a sample container with a marker than a piece of lateral flow paper, which in general is more prone to being damaged.
[0062]
[0063] The paper holder 106 in this embodiment comprises two shell parts: a bottom paper holder part 106′ and a top paper holder part 106″ which are connectable to each other. As an option, the top paper holder part 106″ comprises an opening 107 arranged to allow light from passing between the window 184 and the part of the sample container 202 aligned with the window 184 in a particular state of the device 100. As such, the top paper holder part 106″ may not block viewing of the part of the sample container 202 which is aligned with the window 184.
[0064] The device 100 shown in
[0065] The optional cartridge 180 may comprise one or more ventilation holes 801, for example in the bottom cartridge part 180′. By virtue of the one or more ventilation holes 801, the blood sample on the paper strip 104 may dry quicker.
[0066] When a blood sample is provided to the paper strip 104 through the reception opening 108, after an amount of time, a first area 141 and a second area 142 may be present on the paper strip 104. The first area 141 comprises red blood cells which are filtered from the sample of blood by the lateral flow paper. After some flow distance, substantially all red blood cells are filtered out and hence the second area 142 may comprises substantially no red blood cells. The second area 142 may extend towards the distal end of the paper strip 104—or not.
[0067] The second area 142 may comprise serum, including compounds usually present in serum, including, but not limited to proteins and/or amino acids, minerals, fats, other or a combination thereof. A transition area 143 is present between the first area 141 and the second area 142. The transition area 143 may be a particularly small area resembling a line perpendicular to a flow direction of the blood sample through the paper strip 104. The transition area 142 generally comprises a combination of blood cells and serum.
[0068] As visible in
[0069] The person skilled in the art will appreciate that the size of the first area 141, second area 142 and transition area 143 may depend on properties of the lateral flow paper such as width and thickness, and on the volume of the blood sample provided to the lateral flow paper as well as where on the paper 104 strip the sample is provided.
[0070]
[0071] Also shown in
[0072] As an option, the paper holder 102 is at least partially shaped as a scraper, against which a user may scrape his finger. When this finger is punctured to allow blood to flow out of the finger, using the scraper, blood may be guided into the reception opening 108 onto the paper strip 104.
[0073] As an even further option, at least one of the top paper holder part 102′ and the bottom paper holder part 102″ comprises one or more support protrusions 197. Preferably, at a distal end of a support protrusion 197 which contacts the paper strip 104, the contact area is as small as possible to prevent blocking the flow of blood through the paper strip 104. Hence, the support protrusions may be for example shaped at least partially as a pyramid, triangle, sphere, any other shape, or any combination thereof. Different support protrusions 197 may be shaped differently.
[0074] When both the top paper holder part 102′ and the bottom paper holder part 102″ comprise a support protrusion 197, these support protrusions 197 may be aligned such that they contact the paper strip 104 at opposite sides substantially at the same location. As such, the paper strip 104 may be clamped at this location, as is visible in
[0075] In general, two or more components may be connected by virtue of a clamping connection, forced connection with for example one or more springs, a shape connection wherein for example a part of a first component latches on or fits into to a second component, a glued connection, a welded connection, any other means of connection, or any combination thereof. This in particularly applies to two or more shell parts which may form components such as the paper holder, paper cover body and cartridge.
[0076] The two shell parts which may form at least part of the paper cover body 106, as shown in
[0077]
[0078] The test tube 202 comprises a storage volume 204 provided in a storage part 203 of the test tube 202. As an option, the test tube 202 further comprises a foot part 205 providing a hollow chamber 206. The test tube 202 may be placed on a pin by sliding the foot part 205 over such a pin such that the pin is inserted into the hollow chamber 206. The opening of this hollow chamber 206 faces away from the storage volume 204. Test tubes 202 without the hollow chamber 206 are also envisioned. The foot part 205 may be used to shape the test tube 202 to comply with standard sizes which are compatible with conventional laboratory equipment.
[0079] The grinder 220 comprises a grinder body 222 and an optional gripper part 224 connected to the grinder body 222. One or more protrusions 225 of any shape may extend from the gripper part 224 to improve gripping of the grinder 220, for example with a persons fingers of which a gripper part comprised by a machine. The gripper part 224 may have a larger outer diameter than the gripper body 222, as visible for example in
[0080] The grinder body 222 defines a grinder storage volume 226 and comprises a top opening 227 at an—in use—top side of the grinder body 222. The grinder body 222 further comprises one or more through holes 228, which provide a fluid connection through the grinder body 222 into the grinder storage volume 226. Preferably, the one or more through holes 228 are provided in an in use bottom halve of the grinder body 222. Even more preferably, the one or more through holes 228 are provided substantially as far away as possible from the top opening 227.
[0081] The grinder body 222 for example comprises a base part 234 and a cylindrical wall 236 protruding from the base part 234. For example, the base part 234 may be at least partially flat, spherical, have any other shape, or any combination thereof.
[0082] As a further option, on an outer wall of the grinder body, one or more grinding protrusions 229 are provided extending away from the storage volume 226. In the embodiment of
[0083] The sample container assembly 200, as a further option, comprises a cap 230 arranged for substantially liquid-tightly sealing off the top opening 227 of the grinder body 222. At least one of the cap 230 and the grinder body 222 may comprise a resilient material arranged to elastically deform to correspond to the shape of the other of the cap 230 and the grinder body 222, to form a liquid-tight seal.
[0084] In use, a piece of lateral flow paper comprising blood serum, as an example of a blood sample, may be placed into and/or onto the bottom of the storage volume 204 of the test tube 202. In order to fit the piece of lateral flow paper into the storage 204, a pestle may be used to push the piece of paper entirely into the storage volume 204. The pestle may be automatically operated by a machine. Furthermore, a liquid such as a buffer liquid may be provided to the storage volume 204 as well.
[0085] When the piece of lateral flow paper and the liquid have been placed inside the storage volume 204, the grinder 220 may be placed into the storage volume 204 as well. Hence, an outer shape of at least part of the grinder body 222 may correspond to the test tube 202 such that it may fit at least partially into the storage volume 204. Preferably, the outer shape of the grinder body 222 is substantially complementary to the storage volume 204.
[0086] When the grinder 220 is placed into the storage volume 204, the piece of lateral flow paper is positioned between an outer wall of the grinder body 222 and an inner wall 207 of the storage volume 204. By rotating the grinder 220 inside the storage volume 204, for example around an axis substantially perpendicular to the top opening 227, the piece of lateral flow paper is agitated within the liquid. This may enhance mixing of the piece of lateral flow paper and the liquid, in particular with blood serum components present on the lateral flow paper and the liquid. In examples, at least part of the piece of lateral flow paper may break into smaller pieces and/or at least partially disintegrated to enhance at least partial dissolution of at least part of serum components in the liquid added.
[0087] The method of grinding may further comprise may further comprise moving the grinder 220 at least partially in and out of the storage volume 204 during and/or between rotating the grinder 220, i.e. a rotational and/or lateral movement of the grinder 220 relative to the storage volume 204.
[0088] By virtue of the one or more through holes 228 of the grinder body 222, the liquid with dissolved components of the blood serum may enter the grinder storage volume 226. After some time, the fluid level inside the grinder body 222 may correspond to the fluid level inside the storage volume 204 of the test tube.
[0089] Finally, for example, the liquid inside the grinder body 222 may be extracted from the grinder body 222 using for example a pipette through the top opening 227. This liquid may be substantially free of lateral flow paper, which may be left behind between the outer wall of the grinder body 222 and the inner wall 207 of the storage volume 204.
[0090]
[0091] The protrusions 209 may aid in the cutting, tearing, rupturing or otherwise disintegration of a piece of lateral flow paper placed between the protrusions 209 and the outer wall 221 of the grinder 220. When the grinder 220 comprises one or more grinding protrusions 229, when the grinder 220 is placed into the storage volume 204, these grinding protrusions 229 may contact the protrusions 209 of the test tube 202, or may at least be aligned with the protrusions 209 of the test tube 202.
[0092] The protrusions 209 may additionally or alternatively be used to decrease a contact surface area between the grinder body 222 and the inner wall 207 of the storage area 204, which may reduce the friction force between the grinder body 222 and the inner wall 207 when the grinder body 222 is rotated relative to the inner wall 207. For example, one more more of the protrusions 209 may comprises an outer surface which is partially spherical. Such a spherical shape may be used to resemble a point contact with the grinder body 222, which has a particularly low contact surface area. In other embodiment, the protrusions may have differently curved shapes, facetted shapes, for example pyramid-like shapes, other, or a combination thereof.
[0093] As an even further option shown in
[0094] For example, as shown in
[0095] The test tube 202 as shown in
[0096] As another example, one or more ribs 242 may be provided on an outer surface of the test tube 202. The one or more ribs 242 may extend substantially radially from the test tube 202 and extend substantially parallel to an elongation direction of the test tube 202.
[0097] As a further option, a further rib 244 may be provided on the outer surface of the test tube 202. The further rib 244 extends substantially radially from the outer surface and at least partially circumferentially surrounds the outer surface of the test tube 202.
[0098] In general, the outer surface of the test tube 202 may be provided with any number of protrusions and/or indentations which may be engaged by one or more clamping devices to fixate a position and/or orientation of the test tube 202.
[0099] Next to the device 100 and the sample container 200, a method of processing a sample of blood on a piece of lateral flow paper is envisioned. The paper strip 104 is an example of such a piece of lateral flow paper. Embodiments of the method will be elaborated on in conjunction with the figures.
[0100] In a first method step, the paper holder 102 is released or disconnected from the paper cover body 106 to expose a paper strip 104 as a piece of lateral flow paper held by the paper holder 102. Prior to this first method step, the device 100 may be in the connected state shown in
[0101] When the device 100 comprises a cartridge 180, the cartridge 180 may be removed prior to the first method step or after the first method step. Hence, prior to the first method step, the paper holder 102 together with the paper cover body 106 may be pulled out of the cartridge, as for example shown in
[0102] In a second method step, on the exposed part of the paper strip 104, a transition between the first area 141 and the second area 142 and the transition area 143 in particular may be identified. In general, it may be sufficient to identify two of the first area 141, second area 142 and the transition area 143 to also identify the third of the first area 141, second area 142 and the transition area 143.
[0103] The paper strip 104 may be cut in a third method step. It may be preferred to analyse only blood serum, and/or it may be preferred to have an as less as possible number of red and/or white blood cells in a sample that is to be processed. By cutting the paper strip 104 based on the determined transition area, the second area 142 may be separated from the first area 141. Preferably, the paper strip 104 is cut below the first area 141, either just below the first area 141, in the transition area 143, just below the transition area 143 or within the second area 142. By using this way of cutting, a piece of paper substantially without red and/or white blood cells may be obtained. The first area 141 of the paper strip 104 may be used for different purposes than the second area 142, for example for DNA analysis or Hb-chromatography.
[0104] Since red blood cells reflect different wavelengths of light than blood serum, an optical sensor unit may be used to determine a location where to cut the paper as described above.
[0105] The optical sensor unit may be arranged for sending an optical signal to at least part of the lateral flow paper and for receiving a reflected optical signal from the lateral flow paper.
[0106] For example, the optical signal reflected by the paper strip 104 and compound provided therein comprises light with wavelengths corresponding to red blood cells, which may be indicative of light reflected from the first area. The amount of light with wavelengths corresponding to red blood cells reflected may be lower or even significantly lower in the transition area and the second area 142 on the paper strip. This point may be used to electronically identify a transition between the second area 142 and the first area 141. The cut location may be defined in the transition area or other the transition point—or at a pre-determined distance below the transition area or other the transition point.
[0107] As an optional method step, the length and/or surface area of the second area 142 may be determined or measured, for example using the optical sensor unit. Using data indicative of the length and/or surface area of the second area 142, the amount of liquid to be added to the test tube may be determined to have a specific dilution of the serum after grinding. The amount of liquid added is preferably proportional to the length of the paper that has been cut off, optionally with a particular offset of the paper taken into account.
[0108] By virtue of gravity and the weight of the cut off piece of paper, the cut off piece may fall into the sample container 202 when the device 100 is held substantially parallel to gravity vector, with the opening of het sample container facing upwards towards the cut off piece of paper.
[0109] In a preferred embodiment, the paper holder 102 is disconnected or released from the a paper cover body 106 and more preferably, in a direction parallel to the length of the paper cover body 106. In this way, the paper strip 104 is at least partially exposed, as discussed above. This allows the transition between the first area 141 and the second area 142 to be identified or more conveniently identified.
[0110] Furthermore, this allows the paper strip 104 to be cut as described above. After the cut, the part of the paper strip 104 not held by the paper holder 102, the part comprising no or virtually no red blood cells, falls in the sample container 202. Next, as discussed above, the paper part cut off may be pushed in the sample container 202, using for example a pestle.
[0111] Before or after the cut off piece of paper is deposited into the sample container 202, a buffer liquid may be added into the sample container. Next, the grinder, for example shown in