MICROFLUIDIC APPARATUS AND METHOD
20220168734 · 2022-06-02
Inventors
- Thomas Michael WILLSHARE (Newcastle upon Tyne, Tyne and Wear, GB)
- Hojjat MADADI (Newcastle upon Tyne, Tyne and Wear, GB)
- James BENNETT (Newcastle Upon Tyne, Tyne and Wear, GB)
- Philip SCULLY (Newcastle upon Tyne, Tyne and Wear, GB)
Cpc classification
B01L2400/0677
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/044
PERFORMING OPERATIONS; TRANSPORTING
B01L3/5027
PERFORMING OPERATIONS; TRANSPORTING
B01L2200/16
PERFORMING OPERATIONS; TRANSPORTING
B01L3/502715
PERFORMING OPERATIONS; TRANSPORTING
B01L2200/141
PERFORMING OPERATIONS; TRANSPORTING
B01L2300/087
PERFORMING OPERATIONS; TRANSPORTING
B01L7/52
PERFORMING OPERATIONS; TRANSPORTING
B01L2200/04
PERFORMING OPERATIONS; TRANSPORTING
International classification
Abstract
A microfluidic cassette has a microfluidic cassette body having at least one fluid flow channel and at least one chamber containing reagent. The chamber has a seal to prevent fluid from entering the chamber. The seal is breakable in situ in the cassette body. The cassette body and the chamber are configured such that when the seal is broken, the reagent is exposed to fluid flow in the channel.
Claims
1. A microfluidic cassette comprising: a microfluidic cassette body comprising at least one fluid flow channel, and at least one chamber containing reagent, the chamber comprising a seal to prevent fluid from entering the chamber, wherein the seal is breakable in situ in the cassette body, and wherein the cassette body and the chamber are configured such that when the seal is broken, the reagent is exposed to fluid flow in the channel.
2. The microfluidic cassette of claim 1, further comprising a sealing layer on a surface of the cassette body adjacent to the at least one chamber to prevent fluid outside the microfluidic cassette from contacting the cassette body.
3. The microfluidic cassette of claim 1 or 2, further comprising an insert, wherein the insert comprises the at least one chamber.
4. The microfluidic cassette of claim 3, wherein the seal is breakable in situ when a piercing force is applied to the seal.
5. The microfluidic cassette of claim 4, wherein the cassette body comprises one or more seal breaking mechanisms adapted to break the seal.
6. The microfluidic cassette of claim 5, wherein the one or more seal breaking mechanisms comprise one or more structures adapted to pierce the seal in situ in the cassette body, and wherein the insert is secured within the cassette body and is movable from a first position within the cassette body where the seal is not in contact with the one or more structures to a second position within the cassette body where the seal is in contact with the one or more structures.
7. The microfluidic cassette of claim 6, wherein the one or more structures are adapted such that when the seal is pierced, a fluid flow channel through the chamber is formed, the fluid flow channel in fluid communication with the fluid flow channel of the cassette body.
8. The microfluidic cassette of claim 7, wherein the one or more structures comprises a first annular wall enclosing a first fluid aperture and a second annular wall enclosing a second fluid aperture, and wherein the first and second fluid apertures are in fluid communication with the fluid flow channel of the cassette body.
9. The microfluidic cassette of claim 8, wherein at least one of the annular walls includes a cut-out region around part of the circumference of the wall.
10. The microfluidic cassette of any of claims 6 to 9, wherein the cassette body further comprises a cover element arranged to provide a sealed chamber enclosing the one or more structures and the insert.
11. The microfluidic cassette of claim 10, wherein the insert is secured to an inner surface of the cover element.
12. The microfluidic cassette of claim 10 or 11, wherein the cover element is resiliently deformable.
13. The microfluidic cassette of claim 12, wherein the cover element is arranged to hold the insert in the first position and is resiliently deformable to move the insert into the second position.
14. The microfluidic cassette of claim 13, wherein the cassette body further comprises an outer wall enclosing the one or more structures, said outer wall shaped to guide movement of the insert between the first and second position.
15. The microfluidic cassette of any preceding claim, wherein the seal is breakable in situ when exposed to a temperature substantially above atmospheric temperature.
16. The microfluidic cassette of any preceding claim, wherein the seal is breakable in situ when exposed to a directional beam of light, and wherein the microfluidic cassette comprises at least one pathway that allows light to pass through the cassette and contact the seal.
17. A microfluidic diagnostic system comprising: a microfluidic cassette according to any of claims 1 to 16; and a microfluidic diagnostic device adapted to receive the microfluidic cassette, the device comprising: one or more actuators adapted to break the seal of the microfluidic cassette.
18. The microfluidic diagnostic system of claim 17, wherein the one or more actuators comprise an aperture shaped to receive the microfluidic cassette body.
19. The microfluidic diagnostic system of claim 17 or 18, wherein the one or more actuators comprise a moveable actuating member.
20. The microfluidic diagnostic system of any of claims 17 to 19, wherein the one or more actuators comprise a source of heat.
21. The microfluidic diagnostic system of any of claims 17 to 20, wherein the one or more actuators comprise a source of directional light.
22. An insert for a microfluidic cassette body comprising: at least one chamber containing reagent, the chamber comprising a seal to prevent fluid from entering the chamber, wherein the seal is breakable in situ in the cassette body.
23. A method of manufacturing a microfluidic cassette comprising: providing a microfluidic cassette body comprising at least one fluid flow channel; and providing at least one chamber containing reagent, the chamber comprising a seal to prevent fluid from entering the chamber, wherein the seal is breakable in situ in the cassette body, and wherein the cassette body and the chamber are configured such that when the seal is broken, the reagent is exposed to fluid flow in the channel.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0052] Embodiments of the present invention will now be described by way of example only with reference to the accompanying drawings where like parts are provided with corresponding reference numerals and in which:
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DETAILED DESCRIPTION
[0067]
[0068] The system 100 further comprises a microfluidic diagnostic device 104 adapted to receive the cassette 101. The diagnostic device 104 may comprise a cassette receiving region that allows the cassette 101 to be inserted into and interact with the diagnostic device 104. The diagnostic device 104 may further comprise components that enable it to interact with the cassette 101 and perform diagnostic tests on a fluid sample contained in the cassette. For example, the diagnostic device 104 may comprise one or more diagnostic sensing and/or imaging components for conducting diagnostic sensing and/or imaging on the fluid sample (not shown). The diagnostic device 104 may also comprise components for heating and/or cooling the fluid sample.
[0069] The diagnostic device comprises one or more actuators 105. The one or more actuators 105 are adapted to break a seal of a chamber of the cassette 101 in situ as described in more detail below.
[0070] In use the cassette 101 is inserted into the diagnostic device 104 (denoted by large arrow). After the cassette 101 has been inserted into the diagnostic device 104 the seal of the chamber 103 is broken in situ via the one or more actuators 105. A fluid sample is then introduced into a fluid flow channel of the cassette 101 and diagnostic testing is performed on the sample.
[0071] The one or more actuators 105 may comprise an aperture shaped to receive the cassette body 102. That is, the one or more actuators 105 may comprise an aperture shaped to correspond to an outer shape of the cassette body 102. The shape of the aperture is such that that when the cassette body 102 is passed through the aperture, there is a small or negligible amount of clearance around the cassette body 102. Consequently, when the cassette body 102 passes through the aperture, structures extending out from the cassette body 102 will contact the edges of the aperture. As described in more detail below, in certain embodiments this contact can be used to interact with other components of the cassette body 102 to break the seal 103 of the chamber in situ.
[0072] Alternatively or additionally, the one or more actuators 105 may comprise a moveable actuating member. The moveable actuating member may move from a position where it is not in contact with the microfluidic cassette 101 into a position where it is in contact with the microfluidic cassette 101. The moveable actuating member may, after the cassette 101 has been inserted into the diagnostic device 104, apply a force to part of the cassette 101 to break the seal 103 of the chamber in situ.
[0073] Alternatively or additionally, the one or more actuators 105 may comprise a source of heat such as a heating element. The one or more actuators may apply heat to the cassette 101 or a region thereof to cause the seal of the chamber 103 to be broken in situ. As described in more detail below, in this embodiment the seal 103 of the chamber may be composed of or include a material that degrades when heat is applied.
[0074] Alternatively or additionally, the one or more actuators 105 may comprise a source of directional light such as a laser. The one or more actuators 105 may apply directional light to the seal 103 of the chamber to break the seal in situ. As described in more detail below, in this embodiment the seal 103 of the chamber may be composed of or include a material that degrades when subjected to directional light.
[0075]
[0076] The cassette 200 further comprises at least one chamber 203 containing reagent 204. The term reagent is used herein to refer to a substance or mixture for use in chemical analysis or other reactions. In certain embodiments the reagent 204 may be a dried or lyophilised substance. In certain embodiments the chamber 203 may further contain an inert gas such as nitrogen. This may further reduce degradation of a reagent and/or allow a more sensitive reagent to be used. The inert gas may be introduced into the chamber 203 during sealing of the chamber 203 in a nitrogen rich atmosphere.
[0077] In certain embodiments the reagent 204 may be a liquid or gas.
[0078] The chamber 203 comprises a seal 205 to prevent fluid from entering the chamber 203. The seal 205 is breakable in situ in the cassette body 201. The term in situ may be used herein to refer to while the at least one chamber is sealed within the cassette body 201.
[0079] In certain embodiments, the seal 205 is composed of a foil (for example comprising aluminium), a thermoplastic or a polypropylene (PP) foil composite material. Typically the seal 205 is secured (i.e. sealed) via heat-staking, laser welding or a suitable adhesive such as a thin adhesive. In certain embodiments, the seal 205 has a thickness of approximately 20 microns.
[0080] In certain embodiments, the seal 205 may be breakable when a piercing force is applied to the seal and/or when the seal is exposed to a temperature substantially above atmospheric temperature and/or when the seal is exposed to a directional beam of light.
[0081] The cassette body 201 and the chamber 203 are configured such that when the seal 205 is broken, reagent 204 in the chamber 203 is exposed to fluid in the fluid flow channel 202. This may be achieved by locating the chamber 203 adjacent to the fluid flow channel 202. The location of the chamber 203 relative to the fluid flow channel may force fluid in the fluid flow channel 202 to contact the reagent 204.
[0082] The cassette 200 further comprises a sealing layer 206 on a surface of the cassette body 201 adjacent to the at least one chamber 203. The sealing layer 206 may prevent fluid outside the cassette 200 from contacting the cassette body 201 and/or the fluid flow channel 202. The sealing layer 206 may also prevent fluid inside the cassette body 201 and/or the fluid flow channel 202 from leaving the cassette 200.
[0083] In the embodiment shown in
[0084] The cassette body 201 may comprise one or more seal breaking mechanisms for breaking the seal 205. In the example shown in
[0085] As discussed above, the insert 208 is moveable between a first position 213 and a second position 214 within the cassette body 201. In the first position 213 the chamber 203 is not in contact with the structure 209. In the second position 214 the chamber 203 is in contact with the structure 209 and the seal 205 is broken. It will be appreciated that various seal breaking structures may be provided. For example, instead of a single elongate element as shown in
[0086] The one or more structures 209 are adapted such that when the seal 205 is pierced, a fluid flow channel through the chamber 203 is formed, the fluid flow channel 203 in fluid communication with the fluid flow channel 202 of the cassette body 201. This can provide a fluid flow path through the chamber 203 that results in a greater amount of reagent 204 being removed from the chamber 203.
[0087] As discussed above, in certain embodiments the seal 205 may be breakable when exposed to a temperature substantially above atmospheric temperature. In this example, the seal 205 may be composed of, include or be secured using a material having physical properties that change when heat is applied.
[0088] In certain embodiments, the seal 205 may be breakable when exposed to a directional beam of light such as a laser. In this embodiment, the cassette 200 may comprise at least one light conducting pathway that allows light to pass through the cassette 200 and contact the seal 205. The seal 205 may be composed of, include or be secured using a material having physical properties that change when directional light is applied.
[0089]
[0090] The cassette body 301 comprises a seal breaking mechanism comprising a first elongate element 302 as described with reference to
[0091] Typically the cassette body 301 further comprises a fourth elongate element 306 and a fifth elongate element 307 spaced apart from the second and third elongate elements to cooperate with the second and third elongate elements to hold an insert to the cassette body 301.
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[0095] The method comprises providing 401 a microfluidic cassette body comprising at least one fluid flow channel as described herein. The method further comprises providing 402 at least one chamber containing reagent, the chamber comprising a seal to prevent fluid from entering the chamber, as described herein. The seal is breakable in situ in the cassette body. The cassette body and the chamber are configured such that when the seal is broken, the reagent is exposed to fluid flow in the channel.
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[0097] The insert 500 includes a body 501. The body 501 includes a first enclosed region 502. Prior to use, the first enclosed region 502 is filled with reagent and is sealed to provide a reagent containing chamber.
[0098] The body 501 also includes a second enclosed region 503. In this embodiment, the second enclosed region 503 is located opposite to and substantially corresponds in shape with the first enclosed region 502 such that the body 501 has a substantially H-shaped cross section. This makes the insert 500 symmetrical, which can improve the ease with which the insert 500 can be manufactured and filled with reagent prior to use.
[0099] The second enclosed region 503 can be used to secure the insert 500 to another structure such as the cover 800 described with reference to
[0100]
[0101] The cassette body 600 includes a surface that is arranged to overlie one or more microfluidic channels of a microfluidic cassette.
[0102] The cassette body 600 includes first and second apertures 602 603. In use, the apertures 602 603 provide fluid flow passageways with a microfluidic channel located below the cassette body 600.
[0103] The cassette body 600 also includes first and second annular walls 604 605 that extend out from the cassette body 600 and surround the first and second apertures 602 603 respectively. The first and second annular walls 604 605 provide outwardly extending protrusions which can act as seal breaking structures to pierce the seal of an insert on contact.
[0104] The cassette body 600 is arranged to provide an interface with an insert such as the insert described with reference to
[0105] The ends of the first and/or second annular walls 604 605 can be angled, as shown in
[0106] One or both annular walls 604 605 can be provided with a section around their circumference where material has been removed to provide a cut-out region. Advantageously, providing a cut-out region can improve the fluid flow characteristics through a reagent containing chamber by encouraging mixing of fluid and reagent within the chamber. In this embodiment, the first annular wall 604 is provided with a cut-out region 606 while the second annular wall 605 is not.
[0107] The cassette body 600 also includes an outer wall 601. The outer wall 601 encloses the first and second annular walls 604 605 and acts as a guide for movement of an insert towards and away from the first and second annular walls 604 605.
[0108] Typically, the cassette body 600 includes one or more gaskets or beads (a region of the cassette body providing an abutment surface) for sealing with an insert on contact. Providing a suitable gasket or bead can reduce the force required to create a fluid impermeable seal between the cassette body 600 and an insert during use.
[0109] Typically, the gasket or bead is provided as a continuous surface extending around the base of the cassette body 600 between the annular walls 604 605 and the outer wall 601.
[0110] Where a gasket is provided, typically the gasket is provided as a separate component that is arranged to be positioned in the base of the cassette body 600 adjacent to the annular walls 604 605. The gasket can be composed of a thermoplastic elastomer (TPE) material. The gasket can be manufactured using a suitable additive manufacturing process.
[0111] It will be understood that in certain embodiments, a gasket or bead is not provided and the seal between the cassette body 600 and an insert is provided by other means such as the contact between the components.
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[0114] The cover element 800 is arranged to be secured via a fluid impermeable seal to form part of a microfluidic cassette body. The cover element 800 is typically sealed at an end portion 801 to provide an inner chamber 802. The cover element 800 is shaped so that it can enclose a region of the cassette body and an insert.
[0115] The cover element 800 is resiliently deformable. Typically, the cover element 800 is composed of a deformable material such as a thermoplastic elastomer.
[0116] The cover element 800 is arranged so that an insert can be secured to an inside surface of the cover element 800. In this embodiment, the cover element 800 includes a region 803 that is shaped to correspond with the shape of part of an insert to provide a friction fit between the cover element 800 and the insert.
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[0118] The insert 500 has been secured to the inside surface of the cover element 800 and the cover element 800 has been sealed to the remainder of the cassette body 600. For clarity, the insert 500 is shown without any reagent in the chamber and without the chamber having been sealed.
[0119] The cassette insert arrangement 900 will now be described in use with reference to
[0120] The cassette insert arrangement 900 is initially in a ready to use configuration after the cassette has been inserted into a microfluidic diagnostic device. This is shown in
[0121] A moveable actuating member 1000 that is part of a microfluidic diagnostic device is also shown in
[0122] Next, the moveable actuating member 1000 is moved towards the cover element 800. The actuating member 1000 makes contact with and begins to displace the cover element 800 and insert 500 towards the cassette body 600. This is shown in
[0123] The actuating member 1000 continues to displace the cover element 800 and insert 500 towards the cassette body 600. As the insert 500 is moved into the second position, which is shown in
[0124] In this configuration, microfluidic tests can be performed by the microfluidic diagnostic device in which fluid flows through the insert 500 and interacts with reagent contained therein.
[0125] After processing, the actuating member 1000 typically moves away from the cassette body 600, as shown in
[0126] Due to the fluid impermeable seal between the cover element 800 and the cassette body 600, the cassette remains sealed throughout and fluid is prevented from leaking out of the inside of the cassette.
[0127] A method of manufacturing a plurality of sealed inserts will now be described with reference to
[0128] First, a plurality of inserts are loaded onto a carrier structure. The carrier structure can be, for example, a 96-well plate, as known in the art.
[0129] Next, as shown in
[0130] Next, as shown in
[0131] Next, as shown in
[0132] Advantageously, the inserts are shaped so that they can be accurately and conveniently located in pre-determined positions on the carrier structure for processing. This can improve the speed and ease with which the inserts can be filled and sealed. In this example, the inserts 1200 have two correspondingly shaped enclosed regions located at opposite sides, either of which can be used to locate the inserts on the carrier structure.
[0133] A method of providing a cassette insert arrangement on a microfluidic cassette will now be described with reference to
[0134] A sealed insert 1200 is provided, as shown in
[0135] Next, the insert 1200 is secured to an inside surface of a cover element 1204, as shown in
[0136] Next, the cover element and insert are positioned over a portion of a microfluidic cassette body 1205, as shown in
[0137] The cover element 1204 is then secured to the cassette body 1205 to provide a fluid impermeable seal, as shown in
[0138] In certain embodiments, the cover element can be transparent and/or the insert can be coloured. Advantageously, this can improve the ease with which the cassette insert arrangement can be assembled by providing a visual indication of its internal configuration.
[0139] All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. Each feature disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features. The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.
[0140] With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity.
[0141] It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations).
[0142] It will be appreciated that various embodiments of the present disclosure have been described herein for purposes of illustration, and that various modifications may be made without departing from the scope of the present disclosure. Accordingly, the various embodiments disclosed herein are not intended to be limiting, with the true scope being indicated by the following claims.