JP2008275167A - Valve assembly for microfluidic device, and method for opening/closing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a fluid operation valve assembly normally open, and a system, furthermore, a method of closing/reopening/reclosing this assembly. <P>SOLUTION: The valve assembly normally opened is equipped with a base material 22 having a first surface, and a first recess and a second recess 28 are formed in the first surface. A recessed channel 34 can be formed in the first surface. The recessed channel can extend from the first recess to the second recess. The recessed channel can be at least partially defined by a first deformable material with a first elastic modulus. The valve assembly is equipped with an elastically deformable cover, and an adhesive layer 44 contacting with the first surface. This elastically deformable cover is made of a material with an elastic modulus greater than the elastic modulus of the first deformable material. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

(Citation of related application)
No. 10 / 336,274 (filed Jan. 3, 2003), 10 / 336,706 (filed Jan. 3, 2003), and 10 / 403,652 (Mar. 31, 2003). No. 10 / 403,640 (filed on Mar. 31, 2003), No. 10 / 426,587 (filed on Apr. 30, 2003), US Provisional Patent Application No. 60 / 398,851 (July 2002) Claiming priority benefit from 60 / 398,946 (filed July 26, 2002). All US patent applications and US provisional patent applications mentioned herein are hereby incorporated by reference in their entirety.

(Field)
The assemblies, systems, and methods described herein relate to microfluidic devices. More specifically, the present teachings provide a valve for use in a microfluidic device that can be opened and closed to manipulate, process, or otherwise change a micro-sized amount of fluid and fluid sample. Concerning assembly.

(background)
Microfluidic devices are useful for manipulating fluid samples through the use of openable and closable valves. There continues to be a need for valves for use in microfluidic devices, and methods for such valves, that allow large numbers of fluid samples to be processed simultaneously, rapidly and reliably. Yes.

(Summary)
In accordance with various embodiments, a valve assembly is provided. The valve assembly may comprise a substrate having a first surface, with a first recess and a second recess formed in the first surface. A recessed channel can be formed in the first surface, and the recessed channel can be recessed relative to the first surface. The recessed channel can be defined at least in part by a first deformable material extending from the first recess to the second recess and having a first modulus.

  The valve assembly may also include an elastically deformable cover. The elastically deformable cover may comprise a layer of elastically deformable material, the material having an elastic modulus greater than that of the first deformable material. The adhesive layer can contact the first surface of the substrate. The elastically deformable cover may be arranged to cover the recessed channel, and fluid communication between the first recess and the second recess when the elastically deformable cover layer is in an undeformed state. Can be formed.

  In accordance with various embodiments, a system comprising the valve assembly can be provided. The system may further comprise a platform comprising at least one holder for holding the assembly and a first deformer. A drive unit may be able to drive the first deformer towards the assembly and apply the deformation force to at least one of the elastically deformable cover and the deformable membrane of the recessed channel. It may be possible to grant. The first deformer may press the adhesive layer against the recessed channel to prevent fluid communication between the first recess and the second recess.

  According to various embodiments, the closed valve assembly can be reopened. The drive unit of this system may be capable of driving a first deformer comprising a channel blade to deform the elastically deformable cover and recessed channel material. The drive unit may also be able to move the first deformer away from contact with the elastically deformable cover so that the cover is elastically faster than the deformed material of the recessed channel. Return to. Thereby, fluid communication may be formed by the fluid communication opening between the first recess and the second recess.

  According to various embodiments, the reopened valve assembly can be closed again. In order to reclose the valve assembly, the drive unit may comprise a deformer with a contact pad located at one end. The deformer is configured such that the drive unit allows the pad to contact the elastically deformable cover layer and pushes the adhesive of the adhesive layer into the deformation channel, fluid communication between the first recess and the second recess. Can be driven by a drive unit to close.

  In accordance with various embodiments, a method is provided for closing an initially open fluid communication located between two recesses of a microfluidic assembly, then reopening the fluid communication and then reclosing it.

  In accordance with various embodiments, valve assemblies and systems, and methods for opening and closing valve assemblies, process multiple samples (eg, micro-sized quantities of fluids and fluid samples) simultaneously, quickly and reliably. Make it possible to do.

Additional features and advantages of the various embodiments will be set forth in part in the description which follows, and in part will be apparent from the description, or may be learned by practice of the various embodiments. The objectives and other advantages of the various embodiments will be realized and attained by means of the elements and combinations particularly pointed out in the description herein. Accordingly, the present invention provides the following.
(1) Valve assembly, the following:
Substrate, the following:
A first surface;
A first recess formed in the first surface;
A second recess formed in the first surface; and a recessed channel that is recessed relative to the first surface of the substrate and from the first recess to the second A recessed channel, wherein the recessed channel is defined at least in part by a first deformable material having a first modulus of elasticity.
A substrate comprising:
An elastically deformable cover, with the following:
A layer of elastically deformable material having an elastic modulus greater than the elastic modulus of the first deformable material; and an adhesive layer in contact with the first surface of the substrate;
An elastically deformable cover,
Wherein the elastically deformable cover covers the recessed channel and the first and second recesses when the elastically deformable cover layer is in an undeformed state. A valve assembly that forms fluid communication therebetween.
(2) The valve assembly according to item 1, wherein the adhesive layer can come into contact with the recessed channel in a deformed state of the elastically deformable cover.
(3) The valve assembly according to item 1, wherein the base material includes a polycarbonate material.
(4) The valve assembly according to item 1, wherein the base material includes a cyclic olefin copolymer material.
(5) The valve assembly according to item 1, wherein the adhesive layer includes a pressure-sensitive adhesive.
(6) The valve assembly according to item 1, wherein the adhesive layer includes a hot melt adhesive.
(7) System, the following:
A valve assembly comprising:
Substrate, the following:
A first surface;
A first recess formed in the first surface;
A second recess formed in the first surface; and a recessed channel that is recessed relative to the first surface of the substrate and from the first recess to the second A recessed channel, wherein the recessed channel is defined at least in part by a first deformable material having a first modulus of elasticity.
A substrate comprising:
An elastically deformable cover, with the following:
A layer of elastically deformable material having an elastic modulus greater than the elastic modulus of the first deformable material; and an adhesive layer in contact with the first surface of the substrate;
An elastically deformable cover,
Wherein the elastically deformable cover covers the recessed channel and the first and second recesses when the elastically deformable cover layer is in an undeformed state. A valve assembly that forms fluid communication therebetween;
A platform comprising at least one holder for supporting the valve assembly; and a first deformer comprising a drive unit, the drive unit directing the first deformer toward the valve assembly. The first deformer applies a deforming force to at least one of the elastically deformable cover and the deformable material of the recessed channel; Transformer,
A system comprising:
(8) The first deformer can press the adhesive layer against the recessed channel, thereby providing fluid communication between the first recess and the second recess. 8. The system according to item 7, wherein the system is blocked.
(9) The system of item 8, wherein the first deformer comprises a distal tip and an electrical resistance heater at or adjacent to the distal tip.
(10) The first deformer includes a channel blade, and the channel blade is driven by the drive unit to deform the material defining the elastically deformable cover and the recessed channel. The system according to item 7, which is possible.
(11) It is further possible that the drive unit releases the contact of the first deformer with the elastically deformable cover, so that the cover is deformable of the recessed channel. 11. A system according to item 10, wherein the system is elastically restored faster than the material and fluid communication openings provide fluid communication between the first and second recesses.
(12) A system according to item 7, wherein the substrate includes a polycarbonate material.
(13) A system according to item 7, wherein the substrate comprises a cyclic olefin copolymer material.
(14) The system according to item 7, wherein the adhesive layer includes a pressure-sensitive adhesive.
(15) The system according to item 7, wherein the adhesive layer includes a hot melt adhesive.
(16) A valve assembly comprising:
Substrate, the following:
A first surface;
A first recess formed in the first surface;
A second recess formed in the first surface;
A recessed channel that is recessed with respect to the first surface of the substrate and extends from the first recess to the second recess; and a deformation channel; A deformation channel that is recessed relative to the recessed channel and extends from the first recess to the second recess;
A substrate, wherein the recessed channel and the deformation channel are at least partially defined by a first deformable material having a first modulus of elasticity;
An elastically deformable cover, with the following:
A layer of elastically deformable material having an elastic modulus greater than the elastic modulus of the first deformable material; and an adhesive layer in contact with the first surface of the substrate;
An elastically deformable cover,
Wherein, in the deformed state of the elastically deformable cover, a portion of the elastically deformable cover is spaced from the deformation channel, and the first recess and the second recess A valve assembly that forms a fluid communication opening therebetween.
17. The valve assembly according to item 16, wherein the substrate includes a polycarbonate material.
(18) A valve assembly according to item 16, wherein the substrate comprises a cyclic olefin copolymer material.
19. The valve assembly according to item 16, wherein the adhesive layer includes a pressure sensitive adhesive.
20. The valve assembly according to item 16, wherein the adhesive layer includes a hot melt adhesive.
(21) System, the following:
A valve assembly comprising:
Substrate, the following:
A first surface;
A first recess formed in the first surface;
A second recess formed in the first surface;
A recessed channel that is recessed with respect to the first surface of the substrate and extends from the first recess to the second recess; and a deformation channel; A deformation channel that is recessed relative to the recessed channel and extends from the first recess to the second recess;
A substrate, wherein the recessed channel and the deformation channel are at least partially defined by a first deformable material having a first modulus of elasticity;
An elastically deformable cover, with the following:
A layer of elastically deformable material having an elastic modulus greater than the elastic modulus of the first deformable material; and an adhesive layer in contact with the first surface of the substrate;
An elastically deformable cover,
Wherein, in the deformed state of the elastically deformable cover, a portion of the elastically deformable cover is spaced from the deformation channel, and the first recess and the second recess A valve assembly forming a fluid communication opening therebetween;
A platform comprising at least one holder for supporting the valve assembly; and a first deformer comprising a drive unit, the drive unit directing the first deformer toward the valve assembly. A first deformer capable of being driven and the first deformer imparting a deforming force to the elastically deformable cover;
A system comprising:
(22) the first deformer comprises a contact pad disposed at one end of the deformer, the first deformer being capable of contacting the elastically deformable cover layer; and 24. The system of item 21, wherein the system can be driven by the drive unit to push an adhesive layer into the deformation channel to close fluid communication between the first and second recesses.
(23) A system according to item 22, wherein the contact pad of the first deformer comprises an electric resistance heater disposed at or adjacent to the one end of the first deformer.
(24) After the drive unit closes the fluid communication opening between the first recess and the second recess, the first deformer makes contact with the elastically deformable cover. 23. A system according to item 22, further capable of being released.
(25) A system according to item 21, wherein the substrate comprises a polycarbonate material. (26) A system according to item 21, wherein the substrate comprises a cyclic olefin copolymer material.
(27) A system according to item 21, wherein the adhesive layer includes a pressure-sensitive adhesive.
(28) A system according to item 21, wherein the adhesive layer includes a hot melt adhesive.
(29) Method, the following:
Providing a valve assembly, the valve assembly comprising:
Substrate, the following:
A first surface;
A first recess formed in the first surface;
A second recess formed in the first surface; and a recessed channel that is recessed relative to the first surface of the substrate and from the first recess to the second A recessed channel, wherein the recessed channel is defined at least in part by a first deformable material having a first modulus of elasticity.
A substrate comprising:
An elastically deformable cover, with the following:
A layer of elastically deformable material having an elastic modulus greater than the elastic modulus of the first deformable material; and an adhesive layer in contact with the first surface of the substrate;
An elastically deformable cover,
Wherein the elastically deformable cover covers the recessed channel and the first and second recesses when the elastically deformable cover layer is in an undeformed state. Forming a fluid communication therebetween;
The first deformer is driven against the elastically deformable cover to deform the cover, and the adhesive layer is pressed against the recessed channel to cause the first recess and the Preventing fluid communication with the second recess,
Including the method.
(30) Item 29 further comprising the step of transferring heat from the first deformer to the adhesive layer when the first deformer is driven relative to the deformable cover. The method described.
(31) The method further includes a step of separating the first deformer from contact with the elastically deformable cover, whereby the adhesive layer causes the deformable material of the cover to move into the recessed portion. 30. The method of item 29, wherein the method is adhered to a channel to prevent fluid communication between the first recess and the second recess.
32. The method of claim 29, further comprising driving the first deformer relative to the elastically deformable cover to deform the deformable material of the recessed channel.
(33) further comprising separating the first deformer from contact with the elastically deformable cover so that the cover is elastically faster than the deformed material of the recessed channel. 33. The method of item 32, wherein the fluid communication occurs between the first recess and the second recess.
(34) A method of closing fluid communication between a first recess and a second recess of a valve assembly, comprising:
Providing a valve assembly comprising the following:
A substrate, the following: a first surface;
A first recess formed in the first surface;
A second recess formed in the first surface;
A recessed channel, recessed with respect to the first surface of the substrate and extending from the first recess to the second recess; and a deformation channel; A deformation channel that is recessed relative to the recessed channel and extends from the first recess to the second recess;
A substrate comprising:
An elastically deformable cover, which:
An elastically deformable layer; and an adhesive layer in contact with the first surface of the substrate;
An elastically deformable cover,
Comprising the steps of:
Driving the first deformer against the elastically deformable cover, comprising a contact pad disposed at one end of the first deformer, so that the contact pad is Pushing the adhesive of the adhesive layer into the deformation channel and closing the fluid communication opening between the first recess and the second recess;
Including the method.
35. The method of claim 34, further comprising transferring thermal energy from the contact pad of the first deformer to the adhesive.
36. A method according to item 34, further comprising separating the first deformer from contact with the elastically deformable cover.
(37) A method according to item 34, wherein the second recess holds the purified material.

  It is understood that both the above general description and the following detailed description are exemplary and explanatory only and are intended to provide a description of various embodiments of the present teachings. Should.

(Detailed description of various embodiments)
FIG. 1A shows a partial cut-away top view of a substrate layer portion 22 of a fluid operated valve assembly 20 according to various embodiments. At least two recesses 28, 30 can be formed in the substrate layer 22 and can be separated by the intermediate wall 32. The intermediate wall 32 may define a valve region 26 that may be manipulated to control fluid communication between the two recesses 28, 30. The intermediate wall 32 may be formed from a deformable material, which may be inelastic or elastically deformable. According to various embodiments, the entire substrate layer 22 may include a material that is inelastically or elastically deformable.

  In accordance with various embodiments, the substrate layer 22 of the assembly 20 can include a single layer of material, a coated layer of material, a multilayer material, and combinations thereof. Various other features (eg, dimensions, different levels and layers of recesses, and other properties) of the substrate layer 22 are described, for example, in US patent application Ser. No. 10 / 336,274 to Brying et al. (January 3, 2003). Which is described in the application (hereinafter referred to as Bryning et al.), Which is hereby incorporated by reference in its entirety, the exemplary substrate is a non-brittle plastic It can be made from a single layer substrate of material, such as polycarbonate or TOPAS (plastic cyclic olefin copolymer material available from Ticona (Celanese AG), Summit, New Jersey, USA).

  According to various embodiments, plastic can be used to form a component of valve assembly 20 (eg, substrate layer 22). Plastics can include polycarbonate, polycarbonate / ABS blends, ABS, polyvinyl chloride, polystyrene, polypropylene oxide, acrylics, blends of polybutylene terephthalate and polyethylene terephthalate, nylon, blends of nylon, and combinations thereof. Additional materials used to form the valve assembly 20 are disclosed, for example, in Bryning et al.

  In accordance with various embodiments, the substrate layer 22 can be a material that can withstand thermal cycling between 60 ° C. and 95 ° C. (eg, as experienced during performing a polymerase chain reaction (PCR)) (eg, Glass or plastic). Furthermore, this material is sufficiently strong to withstand the forces required to achieve manipulation of the fluid sample through assembly 20 (eg, the centrifugal force required to spin and manipulate the sample within assembly 20). Should.

  1B is a cross-sectional side view of the valve 26 shown in FIG. 1A as viewed along line 1B-1B in FIG. 1A. The valve 26 may comprise an elastically deformable cover, which comprises a cover layer 42 and an adhesive layer 44. The adhesive layer 44 may comprise, for example, a pressure sensitive adhesive or a hot melt adhesive disposed between the substrate layer 22 and the elastically deformable cover layer 42. The elastically deformable cover can be attached to the surface 24 of the substrate layer 22 by any conventional attachment procedure. For example, the cover layer 42 can be heat welded to the surface 24 of the substrate layer 22. According to various embodiments, the elastically deformable cover layer 42 and the adhesive layer 44 can be transparent. However, according to various embodiments, either or both of these layers can be opaque.

  According to various embodiments, the elastically deformable cover may cover a portion of the substrate layer 22 that includes a recess in an area where a portion of the substrate layer 22 is deformed. For example, the cover may cover any number of recesses aligned in series, all of these recesses, or an area that includes the intermediate wall 32. The cover may partially cover one or more recesses, chambers, inlet ports, tubes, and the like. The cover layer 42 of the cover can have elastic properties that are deformed when the deformer contacts and deforms the intermediate wall 32 (eg, below the cover layer 42 as disclosed in Brying et al.). In addition, this cover can be temporarily deformed.

  As shown in FIG. 1B, the height of the intermediate wall 32 between the recesses 28, 30 can be formed to have a recess relative to the surface 24 of the substrate layer 22, thereby providing a recess channel 34. Form. Further, the pessimistic recess portion of the intermediate wall 32 can be flush with the top surface 24 of the substrate layer 22 comprising the recesses of the assembly 20. As shown in FIG. 1B, in the undeformed state of the cover layer 42, the recessed channel 34 of the intermediate wall 32 may form a fluid communication 36 between the first recess 28 and the second recess 30. Therefore, in the non-deformed state of the elastically deformable cover, the valve 26 is normally open.

  According to various embodiments, the following is the ability of the valve 26 of the fluid operated valve assembly 20 to be closed using, for example, mechanical pressure and temperature, and the valve 26 is repeatedly rereleased and then repeatedly reclosed. Describe the ability. Specifically, the following describes how the adhesive layer 44 is manipulated to open and close the valve 26.

2A and 2B show a top view and a cross-sectional side view, respectively, of the valve 26 of the fluid operated valve assembly 20 in a first valve closed state. In FIG. 2B, the valve 26 is shown in deformed contact with a first deformer 48 disposed after and during the first valve closed state. The first deformer 48 may have a length that extends in the direction from the first recess 28 to the second recess 30. This length can be at least as long as the length of the intermediate wall 32, or the first deformer 48 can be shorter than the length of the intermediate wall. As best seen in FIG. 2B, the drive mechanism 46 moves the first deformer 48 in a direction toward the cover layer 42 so that the contact surface 54 of the first deformer 48 is moved to the cover layer 42. And the adhesive layer 44 may be arranged to deform toward the recessed channel 34. In the first valve closed state, the fluid communication 36 between the first recess 28 and the second recess 30 may be sealed or closed. FIG. 2A shows a top view of the substrate layer portion 22 when the valve 26 is in the first valve closed state. 2A and 3A-6A, the fluid operated valve assembly 20 is shown without an elastically deformable cover so that the features of the substrate layer 22 can be seen without looking through the elastically deformable cover. . According to various embodiments, the substrate layer 22 in the region of the intermediate wall 32 is not necessarily deformed by the first deformer 48 in the first valve closed state. According to various embodiments, the first deformer 48 can be separated from contact with the cover layer 42, and the cover layer 42 can remain adhered to the recessed channel 34 by the adhesive layer 44.

  According to various embodiments, the currently closed valve 26 of the fluid operated valve assembly 20 can be reopened and then reclosed. 2B3B and 4B illustrate, in order, a procedure for reopening the valve 26, starting from a first valve closed state, according to various embodiments.

  As can be seen in FIG. 3B, in the first reopening process, the drive mechanism 46 can further activate the first deformer 48 so that the contact surface 54 of the first deformer 48 is covered by the cover. The layer 42 is deformed into the intermediate wall portion 32 of the substrate layer 22, thereby also moving the adhesive away from the first deformer 48. As a result, the intermediate wall 32 can be deformed by the deformation force of the first deformer 48 to form the deformation channel 40 in the base material layer 22. With reference to FIG. 3B, the first deformer 48 may press the elastically deformable cover layer 42 through the adhesive layer 44 so that the adhesive is effectively between the cover layer 42 and the deformation channel 40. Cannot exist. As a result, as discussed below with reference to FIG. 4B, when the first deformer 48 is removed from contact with the valve 26, the cover layer 42 can be elastically restored to the fluid communication opening. A portion 38 may be formed.

  The deformation channel 40 is also shown in FIG. This figure shows a perspective view of the substrate layer 22 with various recesses and channels formed in the substrate layer. The cover layer 42 and the adhesive layer 44 are omitted in FIG. 7, and the features of the substrate layer 22 are more clearly shown. According to various embodiments, only a portion of the recessed channel 34 of the intermediate wall 32 may be deformed to partially form a fluid communication between the two recesses 28, 30.

  FIG. 3A shows a top view of the substrate layer portion 22 after the first reopening step. According to various embodiments, referring to FIGS. 3A and 7, a first deformer 48 (shown in FIG. 3B) forms a deformed channel 40 in the recessed channel 34 of the intermediate wall 32.

  According to various embodiments, the deformable material of the intermediate wall 32 can be inelastically or elastically deformable. If the deformable material of the intermediate wall 32 is elastically deformable, this material may be less elastic and deformable (having a higher modulus) than the material of the elastically deformable cover layer 42, thereby The cover layer 42 can recover from deformation or return faster than the intermediate wall material, eg, as disclosed in Brying et al. For purposes of example and not limitation, the material of the intermediate wall 32 is described as being inelastically deformable.

FIG. 4B shows a second reopening step that reestablishes fluid communication between the recesses 28, 30. In the second reopening step, the first deformer 48 is moved away from contact with the valve 26, whereby the elastically deformable cover layer 42 moves away from the deformation channel 40 formed in the intermediate wall 32. It becomes possible to recover or return to the original. The inelastically deformable material of the intermediate wall 32 remains deformed or remains deformed for a specified time after the first deformer 48 is removed. When recovering or returning, the portion of the elastically deformable cover layer 42 adjacent the deformation channel 40 of the intermediate wall 32 is spaced a distance from the deformation channel 40 so that the fluid communication opening 38 is Can be formed. Accordingly, fluid communication between the first recess 28 and the second recess 30 can be re-established.

  According to various embodiments, the elastically deformable cover layer 42 may substantially return to its original state after deformation to achieve fluid communication between the two or more recesses. Alternatively, the elastically deformable cover layer 42 can be returned to any degree sufficient to achieve fluid communication. According to various embodiments, the elastically deformable cover layer 42 does not necessarily have to be fully elastic, but is greater than about 25% of its deformed distance, for example, greater than about 50% of its deformed distance. Should be elastic enough to return to large distances.

  The elastically deformable cover layer 42 can be chemically resistant and inert, as can the substrate layer 22. The elastically deformable cover layer 42 can be selected, for example, to withstand thermal cycling between about 60 ° C. and about 95 ° C. as can be experienced during PCR. Any suitable elastically deformable film material (eg, an elastomeric material) can be used. The thickness of the cover layer 42 should be sufficient for the cover layer 42 to be deformed by the deformer 48 as required to reshape the intermediate wall 32 below the cover layer 42. . Under such deformation, the elastically deformable cover layer 42 should not be cut or broken, and should substantially return to its original orientation after deforming the underlying intermediate wall. . Various other features (eg, material properties and bending features) of the elastically deformable cover layer 42 are disclosed, for example, in Bryning et al.

  According to various embodiments, the deformer used can be of various shapes (eg, a shape that leaves a mark on the inelastically deformable material of the substrate layer 22 such that the two recesses or Any fluid communication may be formed between the recessed portions. For example, a straight edge, chisel edge, or pointed blade design is used to form a valley or channel to achieve fluid communication between the two deformers. Other features of the deformer for use are described, for example, in Brying et al.

  The assembly 20 may be configured according to various embodiments with various deformers (eg, one or more open blade deformers 48 (eg, as discussed above and shown in FIGS. 2B, 3B, and 4B)) and 1 One or more closure blade deformers 50 (eg, as discussed below and shown in FIGS. 5B and 6B) may be provided. Such a system or assembly comprises at least one series of recesses, one or more of these recesses being in fluid communication with another, and one or more of these recesses being separated by an intermediate wall Can be used in combination with a processing assembly that is separate from the processing assembly. Further details about this assembly are described below.

  FIGS. 4B, 5B and 6B show the procedure for re-closing the valve 26 and the fluid communication between the first recess 28 and the second recess 30 is re-established by the formation of the fluid communication opening 38. Starting from the state, show continuously. As can be seen in FIG. 5B, in the initial reclose process, the drive mechanism 46 can drive the second deformer 50 in a direction toward the elastically deformable cover layer 42 of the open valve 26, and These can be contacted. The second deformer 50 may comprise a contact pad 52, or similar compliant device, attached to its working end.

FIG. 6B shows a second reclose process, which causes the fluid communication between the recesses 28 and 30 to be side-closed. In the second re-closing process, the drive mechanism 46 can press the contact pad 52 of the second deformer 50 in contact with the elastically deformable cover layer 42. When forced to contact the cover layer 42, the contact pad 52 fits snugly in the shape of the recess formed by the cover layer 42, the adhesive layer 44 and the intermediate wall 32. As a result of the compliant or conformable nature of the pad 52, the material of the pad 52 manipulates the adhesive 45 of the adhesive layer 44 in the region of the fluid communication opening 38, thereby reclosing the valve 26. It can act to do.

  According to various embodiments, the elastic feature of the contact pad 52 allows its shape to change when forced into contact with a structure such as a valve assembly. Contact pad 52 is chemically resistant and may be an inert material. The material of the contact pad can be selected to withstand thermal cycling as may be required during PCR. Any suitable elastically deformable and conformable material (eg, a soft rubber such as silicone rubber) can be used. The particular soft characteristics of the contact pad can be selected depending on the adhesive flow characteristics used in the adhesive layer 44. According to various embodiments, the contact pad 52 may have a memory so that the pad returns to its original orientation after being forced into contact with the valve 26. The thickness of the contact pad 52 should be sufficient so that the pad can be deformed to such an extent that the pad can fill the recesses formed in the cover layer 42 during previous processing steps. .

  Alternatively, the contact pad 52 may be capable of heating the components of the valve assembly. In accordance with various embodiments, the contact pad 52 can heat the adhesive layer 44 when the contact pad is forced into contact with the valve assembly. For example, the contact pad 52 can be formed, in part or in whole, from a thermally conductive material, or a material that can act as a resistance heater, or the contact pad 52 is Shigeura US patent application Ser. No. 10/359, 668 (filed Feb. 6, 2003, which is hereby incorporated by reference in its entirety) and may be arranged as a radiant heater. If the contact pad 52 of the second deformer 50 is formed from a thermally conductive material, the contact pad 52 can be heated, for example, by convection or conduction. If the contact pad 52 of the second deformer 50 is made from a material that can act as a resistance heater, the pad can be heated, for example, by passing a current through the contact pad 52. The contact pad 52 formed as a resistance heater can be arranged with suitable electrical contacts that can provide power to the contact pad 52 at the electrical contacts.

  In accordance with various embodiments, when the contact pad 52 is in place on the cover layer 42, the temperature of the contact pad 52 is in a range such that heat transferred to the adhesive layer 44 can reduce the viscosity of the adhesive 45. obtain. By heating the adhesive 45 and then reducing the viscosity of the adhesive 45, the heat-dissipating contact pad 52 assists in closing or re-closing the valve 26 by promoting the operability of the adhesive 45. obtain. Various types of adhesives (such as pressure sensitive adhesives and hot melt adhesives) can be heated to improve their operability.

  According to various embodiments, a deformer 48 as disclosed with respect to FIGS. 2B-4B may be capable of heating the valve assembly as described above with respect to the second deformer 50. For example, the deformer 48 can be formed from a thermally conductive material, can be formed from a material that can act as a resistance heater, or can be formed as a resistance heater. For example, if the deformer 48 is in the position shown in FIG. 2B and the cover layer 42 and the adhesive layer 44 are forced into contact with the recessed channel 34, the deformer 48 may adhere to the adhesive of the adhesive layer 44. Can be used to close the valve assembly by heating and assisting in adhering or adhering the cover layer 42 to the recessed channel 34. In accordance with various embodiments, the entire transducer 48, or a portion of the deformer 48 (eg, the tip or tip contact portion) is formed from a material that can transfer heat to heat the components of the valve assembly. obtain.

In accordance with various embodiments, after the contact pad 52 has been forced into contact with the elastic stripable cover layer 42 and the adhesive has been manipulated to close the valve 26, the drive mechanism 46 can include a second pressurizer. 50 may be actuated to withdraw from valve 26.

  According to various embodiments, the adhesive layer 44 can be any suitable operable adhesive. For example, a pressure sensitive adhesive or a hot melt adhesive can be used. Examples of pressure sensitive adhesives include silicone pressure sensitive adhesives, fluorosilicone pressure sensitive adhesives, and other polymeric pressure sensitive adhesives. Features considered when selecting an adhesive include, for example, tackiness, viscosity, melting point, and compliance. Application of heat to the adhesive can assist in opening and closing the valve 26.

  According to various embodiments, the adhesive layer 44 can have any suitable thickness and preferably adversely affects either the sample, the desired reaction, or the processing of the sample being processed through the assembly. Not give. The adhesive layer 44 can adhere to the elastically deformable cover layer 42 and back together with the elastically deformable cover layer 42 rather than the underlying inelastically deformable material.

  The complete cycle of closing, reopening, and reclosing the normally open valve 26 according to various embodiments is completed with the reclosed valve 26 as shown in FIG. 6B.

  The sequence of steps shown in FIGS. 1A through 6A and FIGS. 6A-6B can be continuous or in any other order. For example, the valve 26 can be opened starting from a closed position initially, or the valve 26 can be closed from an initially open position as shown in FIG. 5B.

  According to various embodiments, the assembly can be provided as a system comprising a positioning unit that comprises a platform and a holder for aligning the area of the assembly to be deformed with a particular deformer. . A precision positioning drive system is used to allow the particular deformer and valve assembly to move relative to each other so that the features of the valve assembly to be deformed are aligned and aligned with the deformer. obtain.

  In accordance with various embodiments, the fluid handling valve assembly 20 can be disk-shaped, card-shaped, or can comprise other suitable or suitable shapes, specific shapes that can be suitably adapted to specific applications. The assembly 20, or the substrate layer 22 of the assembly 20, can even be formed to provide a series of generally linearly extending recesses or chambers, which can be fluidly connected to each other by valves 26 according to various embodiments. For example, a series of recesses can be provided to the assembly according to various embodiments, whereby centrifugal force is applied to the assembly, and a fluid sample is passed from one of the series of recesses to the series of subsequent recesses. It can be moved by centrifugal force. For example, a disk-shaped assembly comprising a series of radially extending recesses is provided according to various embodiments.

  The assembly 20 can be sized to be conveniently handled by a technician. Depending on the number of chambers in the series or the desired configuration, the assembly 20 may comprise any suitable size (ie, diameter, thickness, length), for example as disclosed in Brying et al. .

  The assembly 20 according to various embodiments may include two or more recesses separated by an intermediate wall, and inlet and / or outlet ports for accessing these recesses. Inlet and outlet ports can be provided through various surfaces of the assembly and can be arranged to provide various fluid communication (eg, an exhaust arrangement as disclosed in Brying et al.).

  In accordance with various embodiments, a method is provided for opening and closing fluid communication between at least two recesses, the at least two recesses being separated by at least one intermediate wall.

  According to various embodiments, the method provides opening and closing of an initially open fluid communication between two recesses. This method includes the step of elastically deforming the cover relative to the substrate layer 22 to close the initially open fluid communication 36 between the two recesses 28 and 30. More specifically, the method drives the elastically deformable cover of the assembly with a first deformer 48 to deform the cover relative to the recessed channel 34 of the substrate layer 22 and initially Includes closing the open fluid communication 36. The first deformer 48 can then be moved away from contact with the elastically deformable cover.

  In order to reopen the fluid communication, the method includes pressing the first deformer 48 against the elastically deformable cover to deform the deformable material of the recessed channel 34. The first deformer 48 is then contacted with the cover so that the cover is elastically restored faster than the deformed material of the recessed channel 34 and the first recess 28 and the second A fluid communication 36 occurs between the recess 30.

  In accordance with various embodiments, a method is provided for forming a barrier for reclosing fluid communication 36 between two recessed portions of an assembly. According to such a method, the deformer 50 having the contact pad 52 disposed at one end is pressed against the elastically deformable cover. The contact pad 52 pushes the adhesive 45 of the adhesive layer 44 into the deformation channel 40 and closes the formed fluid communication opening 38 between the first recess 28 and the second recess 30. The meter 50 is then moved away from contact with the elastically deformable cover.

  In accordance with various embodiments, after the assembly is deformed to form a fluid communication, the deformed assembly can be processed or processed to achieve a product (eg, a reaction product or a purified product). Methods for controlling the flow of fluids or other components in various chambers of a series of chambers include, for example, centrifugal force, electrical force (eg, those used in electrophoresis or electroosmosis), pressure, reduced pressure, gravity, It can be implemented by centrifugal force, capillary action, or any other suitable fluid manipulation technique, or a combination thereof. As a result of the fluid manipulation step, the manipulated fluid is, for example, by PCR under thermal cycling conditions, by sequencing reactions under specified thermal conditions, by purification, and / or by any combination of treatments. It can react in a newly placed chamber.

  Those skilled in the art can now appreciate from the foregoing description that the present disclosure can be implemented in various forms. Thus, although these teachings have been described with respect to particular embodiments and examples of these teachings, the present disclosure is not so limited.

FIG. 1A is a partially cut-away top view of a substrate layer of a substrate layer of a fluid handling valve assembly according to various embodiments, shown in an initial inoperative phase. 1B is a cross-sectional side view of the fluid operated valve assembly shown in FIG. 1A, taken along line 1B-1B of FIG. 1A, in an initial inoperative phase. FIG. 2A is a top view of a substrate layer of a fluid operated valve assembly according to various embodiments, shown in a first stage of operation of the valve assembly, without an elastically deformable cover. 2B is a cross-sectional side view taken along line 2B-2B of FIG. 2A of the fluid operated valve assembly shown in FIG. 2A, with the elastically deformable cover shown in a deformed state corresponding to the first stage of operation. FIG. FIG. 3A is a top view of a substrate layer of a fluid handling valve assembly according to various embodiments, shown in a second stage of operation of the valve assembly, without an elastically deformable cover. 3B is a view of the fluid operated valve assembly shown in FIG. 3A, taken along line 3B-3B in FIG. 3A, with the elastically deformable cover shown in a further deformed state corresponding to the second stage of operation. It is a cross-sectional side view. FIG. 4A is a top view of a substrate layer of a fluid operated valve assembly according to various embodiments, shown in a third stage of operation of the valve assembly, without an elastically deformable cover. 4B is a line of FIG. 4A of the fluid operated valve assembly shown in FIG. 4A with the elastically deformable cover shown partially back from the substrate layer corresponding to the third stage of operation. It is the cross-sectional side view seen along 4B-4B. FIG. 5A is a top view of a substrate layer of a fluid operated valve assembly according to various embodiments, shown before a fourth stage of operation of the valve assembly, without an elastically deformable cover. 5B is a view of the fluid operated valve assembly shown in FIG. 5A, taken along line 5B-5B in FIG. 5A, with the elastically deformable cover shown partially back from the substrate layer. It is a cross-sectional side view. FIG. 6A is a top view of a substrate layer of a fluid operated valve assembly according to various embodiments, shown in a fourth stage of operation of the valve assembly, without an elastically deformable cover. FIG. 6B shows the fluid-operated valve assembly shown in FIG. 6A shown with the elastically deformable membrane further deformed, where the valve assembly is reclosed corresponding to the fourth stage of operation. FIG. 6B is a cross-sectional side view taken along line 6B-6B in FIG. 6A. FIG. 7 is a perspective view of a substrate layer of a fluid operated valve assembly according to various embodiments.

Claims (1)

Invention described in the specification.

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