JP2006515232A - Closure blade and method for a deformable valve in a microfluidic device - Google Patents

Abstract

A microfluidic manipulation system is provided. The microfluidic system includes a blade for manipulating a deformable material and at least one movable support, the movable support contacting a microfluidic device having a deformable feature. Has the ability to move the blade. When the microfluidic device is operably held by the holder, the movable support may position the distal end of the blade relative to the microfluidic device and move the contact end surface of the blade. As a result, it deforms a deformable feature.

Description

(Reference to related applications)
No. 10 / 426,587, filed Apr. 3, 2004; U.S. patent applications 10 / 403,652 and 10/403, both filed Mar. 31, 2003. U.S. Patent Application Nos. 10 / 336,274 and 10 / 336,706, both filed January 3, 2003; and U.S. Patent Application 60, all filed July 26, 2002. / 398,851, 60 / 398,777 and 60 / 398,946 are claimed. All of these applications cited herein are hereby incorporated by reference in their entirety.

(Field)
The present teachings relate to microfluidic assemblies, systems and devices, and methods for using these assemblies, systems and devices. More particularly, the present teachings relate to assemblies, systems, devices, and methods that allow the manipulation, processing, and other changes of micro-sized quantities of fluids and fluid samples.

(background)
Microfluidic devices are useful for manipulating micro-sized fluid samples. There continues to be a need for a reliable valving system in microfluidic devices that allows controlled fluid flow through the microfluidic device. In particular, a need exists for devices and methods that achieve rapid and relatively simple valve actuation to facilitate effective processing of fluid samples through microfluidic devices.

(Summary)
In accordance with various embodiments, a blade for manipulating deformable material in a microfluidic device is provided. The blade may include a support end and an opposing distal end. The distal end includes an end blade portion, the end blade portion includes a first side and a second side, and the first side and the second side are between about 75 ° and about 110 °. Angled with respect to each other at an angle between. The first side and the second side converge on each other in the respective round movement region and intersect the contact tip surface. The contact tip surface can have a length and a width. The first side and the second side can be separated from each other at the distal end of the blade by the length of the contact tip surface. The rounded travel region may each include a radius of curvature that is about 70% to about 95% of the length of the contact tip surface. The third and fourth sides of the blade may be angled with respect to each other at an angle of about 45 ° to about 75 °. Each of the third and fourth sides can intersect at the contact tip surface and can be separated from each other at the distal end of the blade by a transverse hand of the contact tip surface.

  According to various embodiments, a microfluidic manipulation system can be provided with at least one movable blade and at least one movable support. The support can have the ability to be moved in at least a first direction and a second direction. The at least one movable blade may comprise a body defined by the end of the support and the opposing distal end. The support end may be operably connected to at least one movable support. The system can comprise a microfluidic device with at least one feature defined by the deformable material formed therein. The distal end of the blade may comprise an end blade portion comprising at least a first side and a second side. The first side and the second side can converge and terminate at the contact end surface. The at least one movable support may be adapted to position the distal end of at least one blade relative to the microfluidic device when the microfluidic device is operably held by the holder. . The at least one movable support moves the contact end surface such that the contact end surface contacts the microfluidic device to deform the deformable material and at least one feature Can be at least partially closed.

  According to various embodiments, the microfluidic manipulation system comprises a plurality of blades and at least one movable support is relative to the microfluidic device when the microfluidic device is operably held by the holder. It may be adapted to position at least one of the plurality of blades. The at least one movable support moves the at least one contact end surface of the plurality of blades so that at least one respective contact end surface deforms in contact with the microfluidic device. It can have the ability to deform possible materials and at least partially close at least one feature.

  A method for closing at least one feature formed in a microfluidic device is also provided. The method moves the support of the microfluidic manipulation system to bring the distal end of the blade into contact with the microfluidic device to deform the deformable material having at least one feature and at least one feature. A step of at least partially closing may be included.

  In accordance with various embodiments, the method includes contacting a distal end of at least one of the plurality of blades with a microfluidic device to deform the deformable material and at least partially characterize the device. Can be closed. The method contacts two or more distal ends of the plurality of blades with the microfluidic device to deform the deformable material and at least partially close at least one feature. Can do.

  In accordance with various embodiments, a method is provided for closing a channel formed in a microfluidic device. The method can include providing a microfluidic device comprising at least one channel formed therein, at least partially defined by a deformable material. At least one first blade may be provided with a body defined by a support end and an opposing distal end. The distal end of the at least one first blade can be pushed into contact with the microfluidic device, can deform the deformable material, and can at least partially close the at least one channel.

  These and other embodiments can be fully understood by referring to the figures of the accompanying drawings and their descriptions. Modifications recognized by those skilled in the art are considered to be part of the present teachings.

(Detailed description of specific embodiments)
FIG. 1 is a perspective view of a microfluidic manipulation system that can be used to manipulate microsized fluid samples. The system may include a microfluidic device 10, and the device includes a disk or substrate 18 and a path formed therein, the path being a deformable material (eg, an inelastic deformable material). At least in part. The substrate 18 of the microfluidic device 10 can include a plurality of sample wells 14 formed therein. The substrate 18 may be in the form of a disk or a rectangular or square card, or may have any other shape. This sample well is an example of a feature that may be provided in or on the microfluidic device 10. Other features that may be provided in or on the microfluidic device 10 include reservoirs, depressions, channels, biases, adjuncts, output wells, purification columns, valves, and the like.

  As shown in FIG. 1, the plurality of sample wells 14 may be arranged in a line, generally in a line, where each line forms a sample processing path. At one end of each sample processing path, a sample well or output chamber 13 can be provided for the introduction of a fluid sample. The input chamber 13 may comprise a U-shaped bridging surface channel or reservoir, which comprises an input port 15 disposed at one end thereof. In accordance with various embodiments, and as shown in FIG. 1, more than one row that constitutes each sample processing path can be placed side by side on or on the substrate so that multiple samples can be It can be processed simultaneously in one microfluidic device 10. For example, 96 sample processing paths can be arranged per side so that a set of processing paths can form the microfluidic device 10. Further, for example, two or more sets of 96 sample processing paths can be placed in a single microfluidic device 10.

  As shown in FIG. 1, a portion of the substrate 18 has an intermediate wall 16 that can interrupt fluid communication between adjacent sample wells 14 in one row or one path when the intermediate wall 16 is in an undeformed state. Can be formed. The intermediate wall 16 can be forced to deform with the open blade 12 to selectively achieve fluid communication 11 between two or more adjacent sample wells 14 in the sample processing path. By selectively placing the sample wells 14 in each row, a micro-sized fluid sample is continuously processed through each path from one sample well 14 to an adjacent sample well, etc., through each sample processing path. obtain. According to various embodiments, the open blade can be made from a relatively rigid material. For example, stainless steel and hard aluminum can be used to form an open blade.

  FIG. 2 is an enlarged view of the microfluidic device 10 shown in FIG. 1 and illustrates a portion of a sample processing path comprising two sample wells 14 a, 14 b formed in a substrate 18. In an undeformed state of the substrate 18 (not shown), fluid communication between the two sample wells 14a, 14b can be interrupted, interrupted or obstructed by the intermediate wall 16 disposed between the sample wells 14a, 14b. The intermediate wall 16 may be at least partially formed from a deformable material (eg, an inelastic deformable material). In various embodiments, the inelastically deforming material that forms the intermediate wall 16 can be the same material that is used to form the substrate 18 and can be an integral part of the substrate 18.

  The inelastically deforming material forming the intermediate wall 16 can be selectively deformed by the open blade end, so that a recess or channel 19 is formed extending between the two sample wells 14a, 14b, Can create a fluid communication between the two sample wells 14a, 14b.

  As shown in FIG. 1, the surface of the substrate 18 formed with the sample well can be covered with an elastically deformable cover sheet 20. The cover sheet 20 can be made of, for example, plastic, an elastomeric material or other elastically deformable material. When included, the elastic and deformable cover sheet 20 can be attached to the substrate 18 with an adhesive (eg, a layer of pressure sensitive adhesive, hot melt adhesive, etc.). Alternatively, the elastically deformable cover sheet 20 can be attached to the substrate 18 by another attachment mechanism (eg, by thermal melting, clamping, screws, nails, friction fit, etc.). According to various embodiments, either or both of the elastic deformable cover sheet 20 and the adhesive can be transparent and / or translucent. Alternatively, according to various embodiments, either or both of the elastically deformable cover sheet 20 and the adhesive can be opaque, non-transparent and / or translucent.

  According to various embodiments, the microfluidic device 10 may form part of a microfluidic assembly or system 38 as shown in FIG. 19 as discussed below.

  A system or assembly according to various embodiments may include various deforming blades (eg, one or more open blades and / or one or more closed blades). Such a system can be coupled to a microfluidic assembly that can comprise at least one sample processing path, which comprises at least two sample-containing features that can be placed in fluid communication with each other.

  Referring to FIG. 1, if it is desired to phase shift a fluid sample from one sample well 14 to the other, the movable support is adjacent to the intermediate wall 16 with at least one open blade. In the region, it can be pushed into contact with the elastic deformable cover 20 of the microfluidic device 10. The blade end portion 26 of the opening blade 12 can push the elastically deformable cover 20 into the deformable material of the intermediate wall 16. When fully pushed into the intermediate wall 16 from Nachi, the blade end portion 26 of the opening blade 12 has an elastically deformable cover 20 in between, with a recess 19 in the intermediate wall 16 as shown in FIG. Can be formed.

  FIG. 3 is an end view of the aperture blade 12 of various embodiments, and illustrates the aperture blade 12 after being formed in contact with the recess 19 in the microfluidic device 10. When the aperture blade 12 is fully contracted, the elastic deformable cover 20 will at least partially rebound back toward its initial substantially planar misfortune, while the deformable material of the substrate 18 is If the cover 20 is not elastic, it remains deformed. As a result, a channel 22 is formed, which is defined by the cover 20 and the recess 19 and extends between the samples 14. As shown in FIGS. 2 and 3, the recess 19 is defined by a sidewall comprising a first sidewall portion 19a and a second sidewall portion 19b.

  FIG. 2 illustrates a close-up perspective view formed in the substrate 18 by the aperture blade 12. According to various embodiments, the recess 19 and then its sidewalls 19a and 19b can present various cross-sectional shapes depending on the blade end design of the aperture blade 12. For example, an open blade design (straight end, kaiser end, or pointed blade design) can be used to form a hand, recess in the disk portion 18. According to various embodiments, the shape of the blade end portion 26 of the aperture blade 12 and the force applied to the microfluidic device by the aperture blade 12 are designed to protect the aperture blade 12 from being cut or torn through the cover 20. Is done.

  Accordingly, the deformable portion of the microfluidic device 10 can be deformed by the open blade 12 to establish fluid communication between the sample wells 14. The deformable portion may be a portion of a deformable valve of the type described in US application 10 / 398,851, filed July 26, 2002, which is hereby incorporated in its entirety. Incorporated by reference and referred to as ZBIG valves.

  Various structural characteristics and features of the microfluidic components (eg, substrate 18 material, cover 20 material and adhesive components) are as disclosed in US Provisional Application No. 60 / 398,851. obtain.

  The substrate 18 of the microfluidic device 10 may comprise a single layer material, a coated layer material, a multi-layer material, and combinations thereof. More particularly, the substrate 18 may be made from a single layer of non-fragile plastic material (eg, a polycarbonate or TOPAZ material, a plastic cyclized olefin copolymer material available from Ticona (Celanese AG), Summit, New Jersey, USA). .

  The elastic deformable cover 20 may have elastic properties that allow it to change transiently when the deforming blade contacts. However, this is in contrast to the more inelastic deformable material of the substrate 18, where the elastic deformable cover layer 20 is sufficient to achieve fluid communication between the more or less basic sample wells 14. Return to the original direction. The PCR type material is used as or with an elastic deformable cover 20. Polyolefin films, other polymer films, copolymer films, and combinations thereof can be used, for example, to form the elastic deformable cover layer 20.

  In accordance with various embodiments, the material forming the components of the microfluidic device is, for example, about 60 when the microfluidic device 10 is exposed when the device is used to perform a polymerase chain reaction (PCR). It may have the ability to resist thermal cycling at temperatures from 0C to about 95C. In addition, the material forming the components of the microfluidic device 10 may have a strength such that the microfluidic device 10 can resist the forces applied when the fluid sample is forced through it. . For example, the material forming the components of the microfluidic device resists the centrifugal forces encountered when rotating the microfluidic device 10 and subsequently transferring the sample from one sample well 14 to another by centripetal motion. can do.

  In accordance with various embodiments, after opening the ZBIG valve 24 by the opening blade 12, the fluid sample retained in the initial sample well can be allowed to move through the resulting channel 20 and to the adjacent sample well. The fluid sample can be pushed to be moved, for example, by centripetal force or gravity. The microfluidic device 10 can be attached to a rotatable platen or span so that centripetal force moves a fluid sample from a sample well positioned radially inward to a sample well positioned radially outward. And move through the open channel 22.

  In accordance with various embodiments, the ZBIG valve 24 is closed to continue processing fluid in a sample well that is placed with the fluid sample outward in the half hair direction, for example, to perform a polymerase chain reaction (PCR). It may be desirable to prevent the fluid sample from moving back radially inward to the sample well. According to various embodiments, and as shown in FIG. 4, a closure blade 30 may be provided to elastically deform or cold form the deformable material forming the channel 22 of the ZBIG valve 24. it can. In particular, the closure blade 30 can be used alone or in combination with one or more additional closure blades to quickly and simply form a deformable material barrier or dam between the sample wells 14. This barrier may at least partially interfere with fluid communication between the sample wells 14, thereby preventing the fluid sample from undesirably moving back to the sample well where the fluid sample was previously held. Can be reduced.

  In various embodiments, the deformable material of the substrate 18 can be struck on either side or both sides, or in the region of the channel 22 portion of the open ZBIG valve 24 or across its width. With one or more closure blades 30, the microfluidic device 10 can be impacted using either a continuous or simultaneous manner, or a combination thereof.

  For example, FIGS. 5 and 6 sequentially illustrate side views of an arrangement comprising two closure blades 30 that deform the microfluidic device 10. At least the blade tip portion 34 of the closure blade 30 can contact the microfluidic card 10 in or near the open channel 22 of the ZBIG valve 24 to at least partially close the channel 22.

  According to various embodiments, the closure blade 30 may contact a deformable material that has not been previously deformed during the channel formation process. For example, as shown in FIG. 5, the closure blade 30 can strike the microfluidic device 10 at a constant distance X from the side walls 19a, 19b of the channel 22. The distance X may correspond to, for example, at least about 0.75 mm from either of the side walls 19a, 19b. According to various embodiments, the distance X may vary proportionally as a function of the size of the sample well and the size of the recess 19 formed in the intermediate wall.

  As shown sequentially in FIGS. 5 and 6, when one or more blade tip portions 34 of each one or more closure blades 30 are used to form an impression 36 in the substrate 18. The substrate 18 can be replaced by a deformable material. By making the impression 36 relatively close proximal to the sidewalls 19a, 19b of the recess 19, the material defining the sidewalls of the recess is as indicated by the pair of arrows 37 and 39, For example, it can be deformed so as to rise upward. As a result, a barrier 40 can be formed between the two sample wells 14. For example, depending on the number of blades used and the blade end portion 34, the bulging deformation of the side walls 19a, 19b is intimately either completely or partially between two adjacent sample wells 14. It can be changed to fluid communication.

  According to various embodiments, by forming the impression 36 and then forming the barrier 40, the deformable material forming the barrier 40 can achieve a fluid tight encapsulation between the cover 20 and the barrier 40. Thereby interrupting fluid communication between adjacent sample wells 14. The deformable material forming the barrier 40 can be contacted with a pressure sensitive adhesive layer disposed between the cover 20 and the substrate 18.

  FIG. 7 is a plan view of the microfluidic device 10. This previously comprises a valve 24 with open ZBIG, which is closed by deformation caused by two closing blades straddling this valve 24. Two impressions 36 are shown, each formed by a closing blade 30 that cuts off the microfluid 10 respectively. Impressions 36 may be formed by either side or both sides of the ZBIG valve 24 channel that is already open, and as described above, each impression is spaced a set distance from the sidewalls 19a, 19b of the recess 19. Can be opened. The formation of the impression 36 allows the ZBIG valve channel sidewalls 19a, 19b to make the barrier 40 deformable and impact the sidewalls so that they contact each other. In FIG. 7, the hot dog bun shape variation illustrates the ZBIG valve channel in the closed state. More particularly, the side walls 19a, 19b are shown in contact with each other at 39.

  When the ZBIG valve 24 is closed and fluid communication between the sample wells is interrupted, the radially outward sample is transferred without moving the fluid sample to the previously occupied sample well in the radially inward direction. It is possible to continue processing the fluid sample placed in the well.

  8-17 illustrate several closure blades according to various embodiments. The blade tip portion 34 of the closure blade 30 is provided with a closure blade designed to provide a desired piece of deformable material, such as a microfluidic device substrate material. For example, the blade tip portion 34 may have a shape such as a channel sidewall that leaves an impression in a deformable material that deforms and deforms the barrier between two previously bonded sample wells. According to various embodiments, the closure blade can be made from a relatively rigid material. Stainless steel and hard aluminum can be used, for example, to form a closing blade.

  FIG. 8 is a side view of a closure blade according to various embodiments. The closure blade 30 may comprise at least four side surfaces; a first side 60, a second side 70, a third side 80, and a fourth side 90 (not shown in FIG. 8). Each side includes a longitudinal extension at the distal end 58 of the closure blade 30 from the support end 50 of the closure blade 30.

  The support end 50 of the closure blade 30 may comprise a main body portion. The main body portion 52 may comprise a coupling mechanism for coupling the closure blade to a movable support. The movable support can be, for example, an actuator for entering and exiting the closure blade to be deformable to contact the microfluidic device 10. Such a movable support 32 is shown in FIG. The coupling mechanism of the closure blade 30 is a feature that allows the closure blade 30 to be fixedly closed to a movable support (eg, one or more openings for stitching or passing a coupling bolt) 56).

  As shown in FIGS. 8 and 9, each of the first side surface 60, the second side surface 70, the third side surface 80, and the fourth side surface 90 is angled with respect to the first portion and the first portion. Each having a second angled portion. For example, the first side surface 60 comprises a first portion 62 and a respective angled portion 64; the second side surface 70 comprises a second portion 72 and a respective angled portion 74; The three side surface 80 includes a first portion 82 and a respective angled 84; and the fourth side surface 90 includes a first portion 92 and a respective angled portion 94.

  According to various embodiments, the first side surface 60 and the second side surface 70 can be opposed to each other and can comprise respective first portions 62, 72, which comprise a third side surface 80 and a fourth side surface. Each of the first portions 82, 92 has a longer, shorter or the same length. Further, the third side surface 80 and the fourth side surface 90 can be opposed to each other, or the first portions 82 and 92 of the third side surface 80 and the fourth side surface 90 can be opposed to each other. .

  The first portions 62, 72 of the respective first side surface 60 and second side surface 70 can extend parallel to each other as illustrated in FIG. The first portion 62 of the first side surface 60 may include a length that is different from the length of the first portion 72 of the second side surface 70. Correspondingly, the first portions 82, 92 of the third and fourth side surfaces 80, 90 can be parallel to each other, as illustrated in FIG. 9, which shows a side view of the closure blade of FIG. The first portion 82 of the third side surface 80 may have a length that is different from the length of the first portion 92 of the fourth side surface 90.

  As shown in FIG. 8, the distal end 58 of the closure blade 30 may comprise a blade tip portion 34. Along the blade tip portion 34, the first side angled portion 64 and the second side angled portion 74 are angled with respect to each other so that they are at the contact tip surface 100. , Converge to and intersect with each other in the round moving regions 102, 104, respectively. Thus, each of the first side surface 60 and the second side surface 70 can terminate the distal end 58 of the closure blade 30 at the respective rounded movement region 102, 104. The angled portion 64 of the first side and the angled portion 74 of the second side are each angled between about 75 ° and about 110 °, or between about 85 ° and about 95 °. They may be angled with respect to each other at an angle between or at an angle between about 87 ° and about 93 °.

  FIG. 9 is a side view of the closure blade 30 shown along the length of the blade. As shown, the first portion 82 of the third side surface 80 and the first portion 92 of the fourth side surface 90 are shown to face each other. Further, at the distal end 58 of the closure blade 30, the third side angled portion 84 and the fourth side angled portion 94 can be angled with respect to each other so that contact is achieved. They converge and intersect at the tip surface 100. Third side angled 84 and fourth side angled portion 94 may be from about 45 ° to about 75 °, or from about 50 ° to about 70 °, or from about 55 °. They can be angled with respect to each other at an angle of about 65 °.

  FIG. 10 is an enlarged view of the blade tip portion 34 of the closure blade 30 shown in FIG. Contact tip surface 100 is formed at the convergent end of third side angled portion 84 and fourth side angled portion 94, which is a curved surface that can be defined by a radius of curvature R. Can be provided. The radius of curvature R of the contact tip surface 100 can be a value from about 0.0025 inches to about 0.0125 inches, can be a value from about 0.0050 inches to about 0.0100 inches, or about 0.0075 inches. It can be. Contact tip surface 100 may comprise a tip 101 at its distal tip, and this tip 101 may provide a linear contact surface along the length of contact tip surface 100.

  FIG. 11 is an end view of the distal end 58 of the closure blade 30 of FIG. The contact end surface 100 shows how it is defined at and by the two pairs of ends of the angled portions of the sides that converge with each other. Specifically, the contact end surface 100 is formed at the ends of the first side angled portion 64 and the second side angled portion 74 that converge with each other and with the third side surface that converges with each other. At the ends of the angled portion 84 and the angled portion 94 of the fourth side.

  12 is an enlarged view of the blade end portion 34 of the closure blade shown in FIG. As shown in FIG. 12, as shown in FIG. 12, the contact end surface 100 may have a length L and a transverse hand W. This length L may extend between the end of the angled portion 64 of the first side and the angled portion 74 of the third side. Further, the transverse hand W may extend between the angled portion 84 of the third side and the angled portion 94 of the fourth side. Edges 132, 134, 136 and 138 may be formed at the intersections of adjacent angled portions, for example, first side angled portion 64 and fourth side angled portion. 94 or at the intersection between the fourth side angled portion 94 and the second side angled portion 74 doors.

  FIG. 12 illustrates a first side angled portion 64 and a second surface angled portion 74 that intersect the contact end surface 100 at each rounded movement region 102, 104. According to various embodiments, the round travel regions 102, 104 are each about 70% to about 95%, or about 75% to about 90%, or about 80% to about 85% of the length L of the contact end surface. Has a radius of curvature. The radius of curvature of each of the round moving regions 102, 104 has a value of about 0.025 inches to about 0.075 inches, a value of about 0.035 inches to about 0.065 inches, or a value of about 0.050 inches. Can have.

  13-17 illustrate various views of a closing blade 30 'with a modified closing blade design according to various embodiments. Features of the closure blade 30 'that are similar to the features of the closure blade 30 have the same number, but are followed by a prime "'" symbol. For example, as shown in FIGS. 13 and 14 and similar to the closure blade 30, the closure blade 30 ′ includes at least four side surfaces; a first side surface 60 ′, a second side surface 70 ′, and a third side surface. 80 ′ and a fourth side surface 90 ′ may be provided. Each side may have a length that extends from the support end 50 'of the closure blade 30' to the distal end 58 'of the closure blade 30'. Similar to the closure blade 30, the support end 50 ′ of the closure blade 30 ′ includes a main body portion 52 ′ that is movable support, such as the movable support 32 shown. A connecting mechanism for connecting the closing blade 30 'to the body is provided.

  As shown in FIG. 13, each of the first side surface 60 ′ and the second side surface 70 ′ can be angled with respect to the first portion, the respective first angled portion and the respective A second angled portion may be provided. For example, the first side surface 60 'can comprise a first portion 62' and respective angled portions 64 ', and the second side surface 70' can be provided with a first portion 72 'and respective angled portions. A portion 74 ′ may be provided. FIG. 14 can extend to a contact end surface 100 'where the third side surface 80' and the fourth side surface 90 'are each disposed at the distal end 58' of the closure blade 30 '. In accordance with various embodiments, each of the closure blades 30 ′ may present features such as longitudinal, transverse, angle, etc., for example, for the comparative features of the closure blade 30 as previously disclosed above. As disclosed.

  As shown in FIG. 13, the first side angled portion 64 ′ and the second side angled portion 74 ′ can be angled with respect to each other so that they are The contact end surfaces 100 ′ converge with each other and intersect. The first side angled portion 64 ′ and the second side angled portion 74 ′ are about 75 ° to about 110 °, or about 85 ° to about 95 °, or about 87 ° to each other. Can be angled at an angle of about 93 ° from the angle.

  FIG. 14 is a side view of the closure blade 30 'along the length of the blade. As shown, the third side surface 80 'and the fourth side surface 90' are shown in opposing relationship to each other and can be arranged to be parallel to each other. At the distal end 58 'of the closure blade 30', the third side surface 80 'and the fourth side surface 90' terminate at the contact end surface 100 '. As shown in FIGS. 13 and 14, the second side angled portion 74 ′ can be cut along the plane 120 so that the plane 120 is at the contact end surface 100 ′. It can be cut through a portion of the formed recess 110. Alternatively, the second side angled portion 74 ′ is a substantially straight flat side surface that is angled to cut through a portion of the recess 110 of the contact end surface 100 ′. It can be arranged as such. As a result, the recess 110 can be at least partially open on the side of the contact end surface 100 ', as shown in FIGS.

  FIG. 15 is an enlarged side view of the blade end portion 34 'of the closure blade 30' as shown in FIG. Contact end surface 100 ′ includes an edge 112. This edge comprises an inner periphery defined in part by the recess 110. The edge 112 may comprise a substantially flat surface and may be defined at least in part by the contact end surfaces 114, 116 having two open spaces.

  FIG. 16 is an end view of the distal end 58 'of the closure blade 30' of FIG. As shown, the first side angled portion 64 ′ and the second side angled portion 74 ′ interact with each other to partially define a portion of the contact end surface 100 ′. Can converge.

  FIG. 17 is an enlarged view of the blade end portion 34 'of the closure blade 30' shown in FIG. The periphery of the edge 112 of the contact end surface 100 ′ is the end of the first side angled portion 64 ′, the end of the second side angled portion 74 ′, the third side surface 80. May be defined at least by the ends of the ends, the ends of the fourth side surface 90, as well as by the recess 110. Along the inner periphery 113 of the edge 112 (where the edge 112 intersects the depression 110), the depression 110 comprises at least one of an LJ shape, a U shape, a V shape, and a partial oval shape. It may have a cross-sectional shape. At the closed end of the recess 110, the recess 110 may include a radius of curvature R 'of about 0.010 inches to about 0.050 inches, or about 0.015 inches to about 0.030 inches. Further, the edge 112 may comprise contact end surface portions 114, 116 that are open with at least two spaces, the surface portions intersecting edge portions 118 so as to form a substantially planar contact end portion 100 '. Can be linked together.

  In accordance with various embodiments, the angled portion 64 'of the first side can have a curved surface along its length. The curved surface may define a curved outer perimeter 122 at the intersection of the end of the first side angular portion 64 'and the edge 112 of the contact end surface 100'. By incorporating a curved outer perimeter 122 along the intersecting edge portion 118, the closure blade 30 ′ is inserted into the microfluidic card 10 without cutting or tearing through the cover 30 ′ along the intersecting edge portion 118. obtain.

  FIG. 18 shows a side view of an arrangement with a closure blade 30 '. This closure blade 30 'can be contacted with the microfluidic device 10' to deformably close the open channel 22. The closure blade 30 ′ has at least two spaced apart contact end surface portions 114, 116 each of the edges 112 when the contact end surface 100 ′ is deformably contacted with the microfluidic device 10 ′. Can be placed in contact with a deformable material that has not been deformed before. For example, the open contact end surface portions 114, 116 can hit the microfluidic device 10 at a set distance X (eg, at least about 0.75 mm) from the side walls 19 a, 19 b of the channel 22. According to various embodiments, the distance X may vary proportionally as a function of the size of the sample well and the size of the recess 19 formed in the intermediate wall. Furthermore, the intersecting edge portion 118 of the contact end surface 100 ′ can be pushed into the microfluidic card 10 in a region across the transverse side of the recess 19.

  Contact end surface 100 ′ and intersecting edge portion 118 with spaced contact end surface portions 114, 116 can deform the sidewalls 19 a, 19 b material along a portion of the surface of the recess 110. For example, the material defining the sidewalls 19a, 19b can be pushed inwardly to form a barrier between the two sample wells 14. Further, the intersecting edge portion 118 can simultaneously deform one or more respective portions of the side walls 19a, 19b to form portions of the side walls.

  As in the previously described embodiments, the barrier formed by the closure blade 30 ′ achieves a fluid tight encapsulation between the cover 20 and the barrier, thereby providing fluid communication between the sample wells 14. Can be interrupted. In accordance with various embodiments, the deformable material forming the barrier can be pushed into contact with the partially deformed pressure sensitive contact agent layer to achieve fluid-type encapsulation.

  As shown in FIG. 19, the microfluidic device 10 may have the ability to be contacted and deformed by a deforming blade or a plurality of stacked deforming blades 30 attached to a movable support 32. In accordance with various embodiments, a microfluidic device 10 is fixedly secured to both the movable support 32 and the deforming blade 30 of the microfluidic assembly or system 38 using a support device (eg, a holder plate 34). Can be supported.

  Various components, systems, and methods that may be used in connection with the closure blades, systems, and methods described herein include US Provisional Patent Applications 60 / 398,777, 60 / 398,851, and 60 /. 399,548 and 60 / 398,946 and the features and methods described in U.S. Patents 10 / 336,274, 10 / 336,706, and 10 / 336,330. It is done. These documents are hereby incorporated by reference in their entirety.

  Those skilled in the art can now appreciate from the foregoing description that the present teachings can be implemented in a variety of forms. Thus, while these teachings have been described in connection with specific embodiments and examples thereof, the true scope of the present teachings should not be so limited. Various changes and modifications can be made without departing from the scope of the teachings herein.

FIG. 1 is a perspective view of a system according to various embodiments with an open blade shown in the process of deforming a microfluidic device. FIG. 2 is an enlarged view of the system shown in FIG. 1, showing two sample wells forming part of the sample processing path and in fluid communication with each other through a connecting channel having a V-shaped cross section. FIG. 3 is a side view of a system with a retracted aperture blade after deforming a portion of the microfluidic device. FIG. 4 is a perspective view of a system according to various embodiments and comprising a closure blade in the process of deforming a microfluidic device. 5 and 6 are sequential side views of a system according to various embodiments and comprising two closure blades before (FIG. 5) and after deformation (FIG. 6) of the microfluidic device. 5 and 6 are sequential side views of a system according to various embodiments and comprising two closure blades before (FIG. 5) and after deformation (FIG. 6) of the microfluidic device. FIG. 7 is a plan view of a modified microfluidic device of various embodiments comprising a previously opened deformable valve closed by two closure blades that form adjacent depressions in the microfluidic device. It is. FIG. 8 is a plan view of a closure blade according to various embodiments. FIG. 9 is an end side view of the closure blade shown in FIG. FIG. 10 is an enlarged end side view of the blade tip end portion of the closing blade shown in FIG. 9. FIG. 11 is an end view of the closure blade shown in FIG. 12 is an enlarged view of the blade tip end portion of the closing blade shown in FIG. FIG. 13 is a plan view of a closure blade design according to various embodiments. 14 is an end side view of the closure blade shown in FIG. FIG. 15 is an enlarged view of the blade tip end portion of the closure blade shown in FIG. 14 and taken along line 34 'in FIG. FIG. 16 is an end view of the closure blade shown in FIG. FIG. 17 is an enlarged view of the blade tip end portion of the closing blade shown in FIG. 16. 18 is a side view of a system incorporating the closure blade shown in FIGS. 13-17 arranged in accordance with various embodiments and for deformation operations in a microfluidic device. FIG. 19 is a perspective view of a microfluidic manipulation system according to various embodiments and comprising a stack of closure blades disposed on a movable support and a microfluidic card disposed on a holder.

Claims (41)

A blade for manipulating deformable material in a microfluidic device, the blade comprising a support end and an opposing distal end;
The distal end comprises an end blade portion comprising a first side and a second side, and a third side and a fourth side, the first side and the second side being about 75 ° and about 110 with respect to each other. Wherein the first side and the second side each converge to each other and intersect the contact tip surface in each round movement region, the contact tip surface Comprises a longitudinal and transverse sides, the first side and the second side being separated from each other at the distal end of the blade by the length of the contact tip surface, and the rounded moving regions are each the length of the contact tip surface The third side and the fourth side are angled with respect to each other at an angle of about 45 ° to about 75 °, the third side and the fourth side Each of the four sides intersects the contact tip surface And they are separated from each other in the distal end of the blade by lateral hand of the contact tip surface, the blade. The blade of claim 1, wherein the first side and the second side are angled with respect to each other at an angle of about 85 ° to about 95 °. The blade of claim 2, wherein the first side and the second side are angled with respect to each other at an angle of about 87 ° to about 93 °. The blade of claim 1, wherein each of the rounded moving regions includes a radius of curvature that is about 75% to about 90% of the length of the contact tip surface. The blade of claim 4, wherein each of the rounded moving regions includes a radius of curvature that is about 80% to about 85% of the length of the contact tip surface. The blade of claim 1, wherein the third side and the fourth side are angled with respect to each other at an angle of about 50 ° to about 70 °. The blade of claim 6, wherein the third and fourth sides are angled with respect to each other at an angle of about 55 ° to about 65 °. A microfluidic manipulation system comprising:
At least one movable support, the support having the ability to move in at least a first direction and a second direction;
At least one blade comprising a body defined by a support end and an opposing distal end, the support end operatively coupled to the at least one movable support The blade;
A microfluidic device comprising at least one feature formed therein, wherein the at least one feature is at least partially defined by a deformable material;
A holder for holding the microfluidic device;
Here, the distal end of the blade comprises a distal blade portion comprising at least a first side and a second side, the first side and the second side converging on and terminating at a contact tip surface. ;
Wherein the at least one movable support is such that the microfluidic device is operably held by the holder and is positioned at the distal end of the at least one blade relative to the microfluidic device. And has the ability to move the contact tip surface so that the contact tip surface contacts the microfluidic device to deform the deformable material and at least the at least one feature Partially closed system. The microfluidic manipulation system of claim 8, wherein the at least one feature is at least one channel including at least one deformable sidewall. The microfluidic manipulation system of claim 8, wherein the end blade portion further comprises a third side and a fourth side, the third side and the fourth side converging and terminating at the contact tip surface. The microfluidic manipulation system according to claim 10, wherein the contact tip surface includes a transverse hand extending between the third side surface and the fourth side surface. The microfluidic manipulation system of claim 8, wherein the contact tip surface comprises a curved surface defined by a radius. The microfluidic manipulation system of claim 12, wherein the contact tip surface comprises a tip and has a linear contact surface at the tip. The first side surface intersects the contact tip surface at a respective first round movement region and the second side surface intersects the contact tip surface at a respective second round movement region. A microfluidic manipulation system as described in 1. The microfluidic manipulation system of claim 14, wherein the contact tip surface comprises a length extending between the first round movement region and the second round movement region. The at least one blade comprises a plurality of blades, each of the plurality of blades comprising a respective body defined by a respective support end and a respective opposing distal end, the plurality of blades Each respective support end is operably coupled to the at least one movable support, and each distal end of each of the plurality of blades is at least a first side and a second side An end blade portion comprising: the first side and the second side converge and terminate at a contact tip surface with each other; and the at least one movable support includes the microfluidic device Adapted to position at least one of the plurality of blades relative to the microfluidic device when operably held by a holder, and At least one movable support has the ability to move at least one contact tip surface of the plurality of blades such that at least one respective contact tip surface is in contact with the microfluidic device. Deforming the deformable material and at least partially closing the at least one feature;
The microfluidic operating system according to claim 8. The at least one movable support moves the respective contact tip surfaces of the plurality of blades simultaneously to contact the at least one feature to simultaneously deform the deformable material; 17. The microfluidic manipulation system of claim 16, having the ability to close the at least one feature at least partially simultaneously. The at least one movable support continuously moves the respective contact tip surfaces of the plurality of blades into contact with the at least one feature to continuously move the deformable material. 17. The microfluidic manipulation system of claim 16, having the ability to deform and at least partially continuously close the at least one feature. The end blade portion of each of the plurality of blades further comprises a third side and a fourth side, the third side and the fourth side converging together and terminating at the contact tip surface. The microfluidic manipulation system according to claim 16. A method for closing features formed in a microfluidic device, the method comprising the following steps:
Providing a microfluidic manipulation system as claimed in claim 8; and moving the support and pushing the distal end of the blade into contact with the microfluidic device to deform the deformable. A method of deforming material to form the at least one feature and at least partially closing the at least one feature. A method for at least partially closing at least one feature formed in a microfluidic device, the method comprising:
Providing a microfluidic manipulation system according to claim 16;
Contacting the distal end of at least one of the plurality of blades with the microfluidic device to deform the deformable material and at least partially close the at least one feature. And pushing at least one other distal end of the plurality of blades into contact with the microfluidic device to deform the deformable material and to convert the at least one feature into at least one portion; A method comprising the steps of: The plurality of blades are pushed into simultaneous contact with the microfluidic device to simultaneously deform the deformable material and at least partially close the at least one feature. The method described. 24. The plurality of blades are pushed into continuous contact with the microfluidic device to continuously deform the deformable material and to continuously deform the at least one feature. The method described. The microfluidic manipulation system of claim 8, wherein the contact tip surface includes an edge and a recess. 25. The recess according to claim 24, wherein the recess comprises at least one of a U-shape, a U-shape, a V-shape, and at least partially elliptical at an inner periphery of the edge where the edge intersects the recess. Micro fluid handling system. The at least one movable support is adapted to position the distal end of the blade relative to the microfluidic device when the microfluidic device is operatively held by the holder; and Moving the contact tip surface so that the contact tip surface contacts the microfluidic card to deform the deformable material and at least partially close the at least one feature. Item 26. The microfluidic operating system according to Item 25. The rim comprises a contact tip surface portion having at least two spaces open, and the at least one movable support has a contact tip surface portion having the at least two spaces open to each of the microfluidic devices. 25. The microfluidic system of claim 24, wherein the microfluidic system has the ability to be moved into contact with a region of the at least one feature on opposite sides. 28. The microfluidic manipulation system of claim 27, wherein the edge further comprises an interconnect edge portion connecting the at least two open contact tip surface portions. 27. The microfluidic manipulation system of claim 26, wherein the first side and the second side include curved surfaces. One of the first side and the second side includes a substantially flat surface, the substantially flat surface being cut through a portion of the recess formed in the contact tip surface. Item 27. The microfluidic manipulation system according to Item 26. A method of closing at least one channel formed in a microfluidic device, the method comprising:
28. Providing the microfluidic manipulation system of claim 27; and moving the at least one movable support to push the distal end of the blade into contact with the microfluidic device. So that the contact tip surface portion having the at least two open spaces deforms the deformable material and at least partially closes the at least one channel. A method of closing a channel formed in a microfluidic device, the method comprising the following steps:
Providing a microfluidic device comprising at least one channel formed therein, wherein the at least one channel is at least partially defined by a deformable material;
Providing at least one first blade comprising a body defined by a support end and an opposing distal end, the distal end terminating at a contact tip surface; and at least the Including pushing the distal end of one first blade into contact with the microfluidic device to deform the deformable material and at least partially close the at least one channel. how to. The contact tip surface of the at least one first blade comprises a contact tip surface portion having at least two open spaces, wherein the contact tip surface portion is configured such that the distal end of the at least one first blade is microscopic. 34. The method of claim 32, wherein when provided to be contacted with a fluidic device, the microfluidic device is contacted on opposite sides of the at least one channel. The at least one blade comprises a plurality of blades, each blade of the plurality of blades comprising a body defined by a support end and an opposing distal end, the opposing distal end comprising: Terminated at each contact tip surface and provided to contact the distal end of the plurality of blades with the microfluidic device to deform the deformable material, and the at least one channel The method of claim 32, wherein the method is closed. The microfluidic device comprises a first region configured on a first side of the at least one channel, and a second region configured on an opposing second side of the at least one channel, and the plurality of devices At least one of the plurality of blades contacts one of the first region and the second region, and the other one of the plurality of blades contacts the other of the first region and the second region. 35. The method of claim 34. 35. The plurality of blades simultaneously urged into contact with the microfluidic device to simultaneously deform a portion of the deformable material and close the at least one channel. the method of. The plurality of blades are pushed into continuous contact with the microfluidic device to continuously deform respective portions of the deformable material and to continuously close the at least one channel. 35. The method of claim 34. The at least one channel is defined by at least one respective sidewall, and the at least one first blade contacts the deformable material at a distance of at least about 0.75 mm from the at least one respective sidewall. 35. The method of claim 32, wherein the method is pushed in. 35. The method of claim 34, wherein the plurality of blades are spaced apart by about 1.0 cm or less from each other. 35. The method of claim 34, wherein the plurality of blades are spaced apart by about 0.5 cm or less from each other. 35. The method of claim 34, wherein the plurality of blades are spaced apart from each other by about 1.0 mm or less.

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