Patent ID: 12251702

DETAILED DESCRIPTION

The present inventors have conceived of new designs for a flowcell cartridge, such as may be used in chemical and biological analysis systems that utilize microfluidic flow structures contained within a glass plate structure. These concepts are discussed herein with respect to the following Figures, although it will be appreciated that these concepts may be implemented in cartridge designs other than the specific example shown, and that such other implementations would still potentially fall within the scope of the claims.

FIG.1depicts an exploded isometric view of an example flowcell cartridge. InFIG.1, the flowcell cartridge100has a frame102that may, for example, be made of molded plastic or other, durable material. The frame may provide a support structure for supporting a glass plate (or a plate of other material, e.g., acrylic or other plastic), such as glass plate114that contains microfluidic flow structures; this plate may also be referred to herein as a microfluidic plate. In this example, the glass plate, which has a first edge122, a second edge124, a third edge126, and a fourth edge128, includes four sets of multiple, parallel microfluidic flow channels that extend along directions parallel to the long axis of the glass plate, e.g., along axes that are parallel to the first edge122and/or the third edge126. To the extent applicable, the terms “first,” “second,” “third,” etc. (or other ordinal indicators) herein are merely employed to show the respective objects described by these terms as separate entities and are not meant to connote a sense of chronological order, unless stated explicitly otherwise herein. The first edge122and the third edge126may be generally orthogonal to the second edge124and the fourth edge128in some implementations, but may be other orientations in other implementations. As can be seen inFIG.2, which depicts an exploded underside isometric view of the example flowcell cartridge ofFIG.1, each set of microfluidic flow structures may terminate in one or more first fluidic ports118and one or more second fluidic ports120. The first and second fluidic ports118and120may be located in a first side116of the glass plate114, although other implementations may only include the first fluidic ports118or the second fluidic ports120on the first side116. The frame102may have a substantially rectangular opening (or opening of another shape)104that is sized to receive the glass plate114; the rectangular opening104may include opposing side walls106that are in close proximity to the first edge122and the third edge126of the glass plate114when the cartridge is fully assembled. As used herein, the term “substantially rectangular” is use to refer to an opening that has an overall rectangular shape, although there may be various features or discontinuities in the overall shape, such as the semi-circular notches along one side wall of the depicted rectangular opening, or the clamp arm slots along the short edges of the rectangular opening104. The opposing side walls106may be spaced apart by an opening width195to allow the first support bracket132and the second support bracket160, and thus the glass plate114, to float within the rectangular opening104for at least some range of movement, e.g., about 1 mm to about 2 mm or less.

The glass plate114may be held in place in the cartridge100through the use of one or more support brackets, such as a first support bracket132and a second support bracket160. In this discussion, only the features of the first support bracket132are discussed in detail, although it is readily apparent from the Figures that the second support bracket160, which may or may not be identical to the first support bracket132, is at least structurally similar to the first support bracket132and may operate in a similar manner.

The first support bracket132may have a first side134(seeFIG.1) and a second side136(seeFIG.2). The first side134may face towards the glass plate114and may have a first indexing feature138, e.g., a molded pin or post, that extends away from the first side134and that is at least long enough that the side of the first indexing feature138that faces towards the glass plate114may contact the glass plate114when the cartridge is fully assembled. The first indexing feature138may be positioned on the first support bracket132such that the first indexing feature138is proximate to, or contacting, the first edge122of the glass plate114when the cartridge is fully assembled. The first support bracket132may also have one or more second indexing features140(an additional second indexing feature140′ is also shown inFIG.1) that may be similar to the first indexing feature138except that each second indexing feature140may be positioned on the first support bracket132such that the second indexing feature140is proximate to, or physically contacts, the second edge124of the glass plate114. The first support bracket132may also include a third indexing feature142, which may be positioned on an opposite end of the first support bracket132from the first indexing feature138. The first indexing feature138and the third indexing feature142, if used, may be separated from one another by a first float gap156, which may be sized to be slightly larger than the plate width130so as to allow the glass plate114to “float” within the confines of the first indexing feature138and the third indexing feature142. The furthest-apart surfaces of the first indexing feature138and the third indexing feature142may similarly define a first indexing feature width157. The opening width195may be wider than the first indexing feature width157so that the first support bracket132may float laterally between the opposing side walls106of the rectangular opening104.

The first support bracket may also include one or more first gaskets144, which may include one or more seals146(each first gasket144, in this example, includes two seals146, each positioned so as to interface with a different first fluidic port118). The first gaskets144may, for example, be insertable into the first support bracket132or may, in some implementations, be co-molded with the first support bracket132(in the latter case, the first gaskets144and the first support bracket132may, in effect, be treated as a single component). The seals may be proud of the first side134and, optionally, the second side136of the first support bracket so that they may compress against the glass plate114and, as discussed later herein, a fluidic port block, respectively. In some implementations, the seal may not be proud of the second side136of the first support bracket, e.g., if the fluidic port block that faces the second side136when the cartridge is installed in an analysis device has a raised boss that may engage with the seal.

The first gasket144may also include a support foot148, which may be provided to prevent or mitigate “rolling” of the first gasket144about an axis passing through the centers of the seals146when the first support bracket132is translated in a direction parallel to the major surface of the glass plate114while the seals146are in contact with the glass plate114. To this end, the support foot148may be offset from a first axis150spanning between the centers of the seals146of the first gasket144along a second axis152perpendicular to the first axis150by some amount so as to provide a moment arm to resist such rolling behavior. The support foot148and the seals146may all be designed to have contact surfaces that contact the glass plate114in concert when the glass plate114is brought into contact with the first gasket144. These contact surfaces may all be parallel to one another to ensure that when the contact surface of the support foot148is in contact with the glass plate114, the contact surface(s) of the seal(s)146are also in good, i.e., not having any misalignment gaps, contact with the glass plate114. In the example cartridge shown, each support bracket includes two first gaskets, although they may be referred to as second gaskets, third gaskets, etc., in the interests of reducing confusion, if needed. It is also be understood that the support foot148, while appearing similar to the seals146, may actually not provide any “sealing” characteristics at all—it may be present solely for the purposes of preventing or mitigating “rolling.”

FIGS.5and6are diagrams illustrating how a seal can roll when the surfaces between which the seal is interposed are translated laterally. InFIG.5, a glass plate514is offset from a fluidic port block564, and a support bracket532with a gasket544is interposed between them. The gasket544has a seal546that is aligned with a fluidic port518′ in the fluidic port block564, but that is misaligned somewhat with a fluidic port518in the glass plate514. As can be seen inFIG.6, when the glass plate514is slid sideways so that the fluidic port518is aligned with the seal546, friction between the seal546and the glass plate514/fluidic port block564may cause the seal546to not slide a commensurate distance—as a result, the gasket544and the support bracket532may tilt or roll slightly, resulting in gaps594appearing between the seal546and the glass plate514/fluidic port block564. This is, of course, undesirable, as it causes leakage.

FIGS.7and8are diagrams illustrating how a gasket with a support foot can prevent the rolling behavior illustrated inFIGS.5and6. As can be seen, the gasket544has been extended to the right and a support foot748has been added to the gasket544. When the glass plate514is slid to the left, as inFIG.6, the support foot748introduces a counter-moment to any potential rolling moment caused by friction between the seal546and the glass plate514/fluidic port block564. This prevents the formation of the gaps594and keeps the seal546in good contact with the surfaces it seals.

The first support bracket132may snap into two opposing first retaining clips108(only one is visible inFIG.2, as the other is obscured by other features of the frame102—however, there are corresponding second retaining clips visible on the opposite end of the frame102that are configured similarly but at a different location). The first retaining clips108may have opposing surfaces110that are separated from one another by a first distance112. The first distance may be greater than a first width158of the first support bracket132, thereby allowing the first support bracket132to float laterally by a small amount when snapped into the first retaining clips108. In some implementations, the amount of float between the first support bracket132and the opposing side walls106, i.e., the opening width195minus the first indexing feature width157, may be smaller than the amount of float between the first support bracket132and the retaining clips108, i.e., the first distance112minus the first width158. Similar relationships may exist for the second support bracket160.

FIG.3depicts a front isometric view of the example flowcell cartridge ofFIG.1in an unexploded/assembled state.FIG.4depicts a rear isometric view of the example flowcell cartridge ofFIG.1in an unexploded/assembled state. As can be seen, the glass plate114is held in place within the frame102by the first support bracket132and the second support bracket160, which, in turn, are held in place by the first retaining clips108and second retaining clips, respectively. The frame may have a first overlapping portion196and a second overlapping portion196′ (seeFIG.2) that overlap with a corresponding first portion197and second portion197′ (seeFIG.1) of the glass plate114. The first portion197may include the second edge124, and the second portion197′ may include the fourth edge128. The overlapping portions196/196′ may prevent the glass plate114from falling out of the front of the frame102, e.g., the glass plate114may be sandwiched between the overlapping portions196/196′ and the first/second support brackets132/160. The glass plate114may still, however, be free to float within the frame to some degree.

FIG.9depicts an isometric view of the first support bracket132of the example flowcell cartridge100ofFIG.1.FIG.10depicts an underside isometric view of the first support bracket132of the example flowcell cartridge100ofFIG.1. In addition to the first indexing feature138, the second indexing feature(s)140, and possibly the third indexing feature142, the first support bracket132may also include first fluidic port indexing features154on the second side136of the first support bracket132(the second support bracket160may have corresponding second fluidic port indexing features as well). As can be seen, the first support bracket has portions that extend beyond the first width158, e.g., the small “teeth” that are located at the four outermost corners of the first support bracket132. These teeth may engage with the first retaining clips108and may allow the first support bracket132to also float along an axis parallel to the first edge122by some limited amount.

In this example cartridge, the glass plate114may float with respect to the support brackets132and160, and the support brackets132and160, in turn, may float with respect to the frame102. Thus, there are two tiers of floating components in the example cartridge. The combination of these different tiers of floating components, as well as the various indexing features provided, allow for the glass plate114and the seals146to be properly aligned with each other and with ports on floating manifold blocks located on equipment that receives the cartridge100.

FIG.11depicts an isometric view of an example receiver for the example flowcell cartridge ofFIG.1. As seen inFIG.11, a receiver162may be provided; the receiver may be a subcomponent of a larger analysis device that utilizes the cartridge100. The receiver162may include a chuck176, against which the glass plate114may be drawn, e.g., by a vacuum, during analysis operations. The receiver162, in this example, may include a pair of first fluidic port blocks164and an opposing pair of second fluidic port blocks166. The first fluidic port blocks164and the second fluidic port blocks166may be configured to float slightly in directions at least parallel to the upper surface of the chuck176(and possibly also in directions perpendicular to the upper surface of the chuck176). The ends of the receiver162may include, for example, a clamping mechanism that may serve to clamp the glass plate114against the chuck176. Such clamping mechanisms may, for example, have clamp arms172that may rotate downwards and contact the upper surface of the glass plate114of the cartridge100when the cartridge100is installed. The receiver162may also include indexing features that are located so as to engage with the support brackets and glass plate114of the cartridge100when the cartridge100is installed. For example, lateral indexing pins168may be placed such that the glass plate114contacts the lateral indexing pins168when the glass plate114is translated laterally along the short axis of the chuck176, and longitudinal indexing pins170may be positioned so as to contact the support brackets of the cartridge100when, for example, one of the longitudinal indexing pins170is moved towards the other longitudinal indexing pins170. In this example, the longitudinal indexing pin170on the left is fixed in space relative to the receiver162, whereas the other longitudinal indexing pin170is configured to slide along an axis parallel to the long axis of the chuck176. The sliding longitudinal indexing pin170may be sprung so as to be biased towards the other longitudinal indexing pin170. The interaction of the various indexing features is explained in more detail below, with respect toFIG.12.

FIG.12depicts an exploded isometric view of the example receiver ofFIG.11and the example flowcell cartridge ofFIG.1. In this example, the cartridge100has been shown in an exploded view, although the various components that form the cartridge would be fully assembled, perFIG.3, prior to the cartridge100being placed in the receiver162.

When the cartridge100is laid on top of the receiver162, the clamp arms172may rotate downward and engage with the top side of the glass plate114. The clamp arms172may also, as they pivot, translate along their rotational axes towards the lateral indexing pins168such that the sides of the clamp arms172engage with the sides of the rectangular notches or clamp arm slots198, thereby causing the entire frame102to translate along the same axis as well. For example, the clamp arm slots198may be sized, e.g., with clamp arm widths173in a direction parallel to the second edge124that are less than the widths of the clamp arm slots198in the same direction, to allow the clamp arms172to swing through the clamp arm slots198freely and, during lateral translation of the clamp arms172, press against the sides of the clamp arm slots198facing away from the lateral indexing pins168, thereby pushing the frame102towards the lateral indexing pins168. During this lateral sliding motion, the frame102will (if not already in such a state) come into contact with the first indexing feature138on the first support bracket132(and a corresponding first indexing feature on the second support bracket160) at indexing feature contact points182located along one of the opposing side walls106. As the frame102continues to be translated towards the lateral indexing pins168, the glass plate114will eventually come into contact with both the lateral indexing pins168and the first indexing features138(see lateral indexing pin contact points184and the indexing feature contact points182along the first edge122of the glass plate114). Eventually, the first indexing features138will be sandwiched between the frame102and the glass plate114(which is pressed against the lateral indexing pins168), thereby locating the first support bracket132and the second support bracket160firmly in space in the lateral direction, i.e., perpendicular to the long axis of the chuck176. This aligns the seals on the first support bracket132and the second support bracket160with the corresponding first fluidic ports118and the corresponding second fluidic ports120, respectively, on the glass plate114.

Subsequent to, after, or in concert with the translation of the frame102towards the lateral indexing pins168, the longitudinal indexing pins170may be caused to move towards one another (one or both may move), thereby contacting the facing edges of the first support bracket132and the second support bracket160and pushing the first support bracket ##32and the second support bracket160towards one another. As the first support bracket ##32and the second support bracket160move towards one another, the glass plate114may come into contact with the second indexing features140(and140′, if present) on the first support bracket132and the second support bracket160. The first support bracket132and the second support bracket160may thus become aligned with the glass plate114and, consequently, the first fluidic ports118and the second fluidic ports120.

After or during such plate alignment, the fluidic port blocks164,166may be raised so that the first fluidic port indexing features154(and corresponding second fluidic port indexing features on the second support bracket160) may be inserted into corresponding alignment holes188on the first fluidic port block164and the second fluidic port block166. As the fluidic port block rises, the first fluidic port indexing features154and the second fluidic port indexing features may engage with the corresponding alignment holes188and force the first fluidic port blocks164and the second fluidic port blocks166into alignment with the first support bracket132and the second support bracket160, respectively. This, in turn, ensures that the corresponding seals146on the respective support brackets132,160line up with the fluidic ports on the first fluidic port blocks164and the second fluidic port blocks166, respectively.

Thus, the cartridge100may have multiple levels of floating components that engage with different sets of indexing features/pins in the cartridge100and located on the receiver162and are moved into precisely aligned positions that cause the fluidic ports, seals, and port block ports to line up, e.g., such that the centerlines of the fluidic ports, seals, and port block ports are, in some implementations, within less than about 0.05 mm of one another, thereby ensuring a high-quality liquid-tight seal. At the same time, some implementations of the cartridge may feature additional features in the floating brackets, e.g., support feet, that may prevent rolling behavior of the seal, thereby ensuring the integrity of any sealed connections. Some of the floating components, e.g., the support brackets, may also act to retain other floating components, e.g., the glass plate, in a manner that prevents stressing the glass plate due to thermal expansion mismatches between the glass plate and the cartridge frame, minor flexure of the cartridge frame, and so forth.

The floating behavior of the various components in the cartridge100may be better understood with reference toFIG.13, which depicts a plan view of the example flowcell cartridge ofFIG.1. For reference purposes, the lateral indexing pins168are shown as dotted circles and the outlines of the clamp arms172are shown as dotted, rounded rectangles, but the remainder of the components shown are part of the cartridge100. The clamp arms172are shown in both an “engaged” position (black line font) in which they are engaged with and pressed against the sides of the clamp arm slots198(seeFIG.2) and a non-engaged position (grey line font), which may be their position prior to translating laterally. The glass plate114maybe able to move laterally by an amount relative to the frame102that is limited by the first and second indexing features138and142, respectively11. The first and second support brackets may be able to move laterally (as well as longitudinally) by a lesser amount, as is shown by the bracket float envelopes180. For example, the first and second support brackets may be able to float laterally by a distance of X, which may be the opening width195minus the first indexing feature width157, relative to the frame, and the glass plate114may be able to float laterally by a distance of Y, which may be the first float gap156minus the plate width130, relative to the first and second support brackets132and160. In some such implementations, Y may be less than X-however, the glass plate114may still float by a larger amount relative to the frame102than the first and second support brackets132and160since the glass plate114has a total overall float relative to the frame102of X+Y. This may allow for considerable adjustment in the positioning of the glass plate.

An example alignment sequence is reviewed inFIGS.14through17, which depict various stages of component alignment that may occur during clamping of an example flowcell cartridge. InFIG.14, the frame1402(shown in solid lines) of a flowcell cartridge is lowered onto a receiver with two floating fluidic port blocks1464(shown in dashed lines). As can be seen, the fluidic port blocks1464are slightly askew due to the fact that both are “floating.” Also visible inFIG.14is the outline of a support bracket1432(dotted lines) and a glass plate1414(dash-dot-dash lines). There are four instances of fluidic ports1418across the glass plate1414. As can be seen, at each fluidic port1418, there are corresponding features belonging to the support bracket (dotted circles) and fluidic port blocks (dashed lines). These correspond, for example, to the holes in the seals146and to the ports in the fluidic port blocks1464. As is evident, there is some alignment between these three separate fluidic flow features at each location, but the alignment is far from ideal, resulting in differently-configured apertures at each location which may cause imbalances in fluid flow.

InFIG.15, the support bracket1432has been fully engaged with the fluidic port blocks1464so that fluidic port indexing features1454(seeFIG.14) are fully inserted into alignment holes1488(also seeFIG.14). The alignment holes1488, for example, may be countersunk and the fluidic port indexing features1454may have conical or rounded tips so that they may engage with one another even if somewhat misaligned; as the fluidic port indexing features1454are more fully engaged with the alignment holes1488, the countersink portion may narrow and force the fluidic port indexing features1454to move towards the center of the alignment holes1488. As can be seen, one of the alignment holes1488for a given fluidic port block1464may be circular, thereby providing both X and Y location constraints, whereas the other may be obround to provide a single degree of constraint, e.g., along only the Y axis, as this may be all that is needed in one implementation to prevent rotation about the other alignment hole1488. It is to be recognized that the alignment holes1488and the fluidic port indexing features1454may also be swapped, i.e., the alignment holes1488may be located on the support bracket1432, and the fluidic port indexing features1454may be located on the fluidic port block1464.

Returning toFIG.15, the interfacing of the cartridge with the fluidic support blocks1464causes the fluidic port blocks1464to come into alignment with each other as well as with the support bracket1432. Consequently, the ports on the fluidic port blocks1464are now precisely aligned with the holes, e.g., the seals, on the support bracket1432. However, the holes/seals on the support bracket1432are not yet aligned with the fluidic ports1418on the glass plate.

InFIG.16, the glass plate1414has been moved upwards to contact second indexing features1440on the support bracket1432; this contact and the upward movement of the glass plate1414causes the support bracket1432to move upwards until it contacts longitudinal indexing pin1470, thus firmly locking the support bracket1432in place in the vertical direction (with respect to the Figure orientation; in reality, this is more accurately called the longitudinal direction)—this aligns the fluidic ports1418in the glass plate1414with the corresponding holes/seals in the support bracket1432in the vertical direction.

Finally, inFIG.17, the frame1402may be pushed towards the lateral indexing pin1468. This causes the inside edge of the frame1402to contact first indexing feature1438, which causes the support bracket1432, in turn, to move towards the lateral indexing pin1468until the first indexing feature1438also contacts the glass plate1414and pushes the opposite side of the glass plate1414into contact with the lateral indexing pin1468. As can be seen, the first fluidic ports1418and the respective seal holes and fluidic port block holes are completely aligned, thereby ensuring a consistently-sized flow aperture and proper seal alignment.

The term “about” used throughout this disclosure, including the claims, is used to describe and account for small fluctuations, such as due to variations in processing. For example, unless otherwise specified herein in a particular context, they can refer to less than or equal to ±5%, of the specified value or value equivalent to the specified relationship, such as less than or equal to ±2%, such as less than or equal to ±1%, such as less than or equal to ±0.5%, such as less than or equal to ±0.2%, such as less than or equal to ±0.1%, such as less than or equal to ±0.05%.

As noted earlier, any use of ordinal indicators, e.g., (a), (b), (c) . . . or the like, in this disclosure and claims is to be understood as not conveying any particular order or sequence, except to the extent that such an order or sequence is explicitly indicated. For example, if there are three steps labeled (i), (ii), and (iii), it is to be understood that these steps may be performed in any order (or even concurrently, if not otherwise contraindicated) unless indicated otherwise. For example, if step (ii) involves the handling of an element that is created in step (i), then step (ii) may be viewed as happening at some point after step (i). Similarly, if step (i) involves the handling of an element that is created in step (ii), the reverse is to be understood.

It is also to be understood that the use of “to,” e.g., “the apparatus is to be interfaced with a receiver of an analysis device,” may be replaceable with language such as “configured to,” e.g., “the apparatus is configured to be interfaced with a receiver of an analysis device”, or the like.

It should be appreciated that all combinations of the foregoing concepts (provided such concepts are not mutually inconsistent) are contemplated as being part of the inventive subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are contemplated as being part of the inventive subject matter disclosed herein. For the sake of brevity, many of those permutations and combinations will not be discussed and/or illustrated separately herein.