Patent Grant
10898895
The present invention relates to the field of fluidic devices that are capable of receiving and transporting a sample liquid. In particular, the present disclosure is directed toward systems, devices, and methods for loading a sample liquid into an assembly, and transferring the loaded sample liquid within the assembly, while minimizing spilling of the sample liquid from the assembly.
Many existing fluidic devices are configured to receive a sample liquid at one location in the fluidic device, e.g., an entry port, and subsequently transfer the sample liquid from the first location in the fluidic device to an alternative location in the fluidic device, e.g., a reservoir. Such fluidic devices comprise continuous fluidic pathways that are configured to transport the sample liquid from the first location in the fluidic device to the alternative location of the fluidic device.
In these existing fluidic devices, transport of the sample liquid within the fluidic device is commonly achieved using pneumatic force. However a gas supply cannot be used to load the sample liquid into the device. In such cases, capillary forces and surface tension are commonly used to trap the sample liquid in a desired location within the device. True capillary features rely on hydrophilic channel walls and channel diameters significantly under 1 mm. Such approaches are appropriate for the collection of several drops of sample liquid, but are inefficient for volumes of sample liquid on the order of 1 mL. Converging channels can be used to partially direct the loading of sample liquid, but the surface tension forces experienced in such channels are limited, and can be hampered by encapsulated gas or changes in shape of the channels.
The novel devices described herein include fluidic devices that are configured optimize transport of sample liquid from a proximal region of the fluidic device to a distal region of the fluidic device. More specifically, the devices described herein enable efficient transport of a precise volume of sample liquid from a proximal region of a fluidic device to a distal region of the device, thereby optimizing the speed and reliability of assays performed using the sample liquid at the distal region of the fluidic device.
The present disclosure relates generally to an assembly that transports a loaded sample liquid from an entry port of the assembly to a reservoir of the assembly, while minimizing spilling of the sample liquid from the assembly.
In one aspect, the disclosure provides an assembly that comprises an entry port and a reservoir. The entry port is located at a proximal region of the assembly, and comprises an inlet and a first gas vent. The inlet defines an opening of the entry port. The inlet of the entry port has a first lateral edge and a second lateral edge. The first gas vent defines another opening of the entry port. Turning to the reservoir of the assembly, the reservoir comprises a distal wall, a first fin, and a continuous fluidic pathway. In some embodiments, the reservoir of the assembly holds a volume of up to 10 milliliters. The distal wall of the reservoir is located at a distal region of the assembly that is opposite the proximal region of the assembly. The first fin of the reservoir extends from the first lateral edge of the inlet of the entry port towards the distal wall. The first fin comprises a first surface and a second surface. In certain embodiments, the first fin increases in thickness as a distance from the entry port increases. The continuous fluidic pathway of the reservoir comprises a converging channel and a first diverging channel. The converging channel is in fluidic communication with the inlet of the entry port, and is defined in part by the second surface of the first fin. In some embodiments, the width of the converging channel decreases linearly as a function of increasing distance from the entry port. The first diverging channel of the continuous fluidic pathway is defined in part by the first surface of the first fin, and is in fluidic communication with the first gas vent of the entry port. To neutralize forces between the converging channel and the first diverging channel at the distal region of the assembly, such that a sample liquid can concentrate at the distal region of the assembly, at a distal end of the first fin (i.e., the portion of the first fin that is closest in proximity to the distal wall of the reservoir), a width of the converging channel is substantially equivalent to, or less than, a width of the first diverging channel. Furthermore, a distance between the distal end of the first fin and the distal wall is substantially equivalent to, or less than, the width of the converging channel at the distal end of the first fin.
In addition to being defined by the first surface of the first fin, in some embodiments, the first diverging channel is further defined by a first lateral wall of the reservoir. In such embodiments, the first lateral wall extends between the proximal region of the assembly and the distal wall. Similarly, in addition to being defined by the second surface of the first fin, in some embodiments, the converging channel is further defined by a second lateral wall of the reservoir. In such embodiments, like the first lateral wall, the second lateral wall also extends between the proximal region of the assembly and the distal wall.
To further support transport of a sample liquid from the entry port into the distal region of the assembly and thereby avoid spilling of the sample liquid from the entry port, in some embodiments, the width of the converging channel at the inlet of the entry port is less than a height of the inlet of the entry port. In further embodiments, the reservoir is taller at the distal end of the first fin than at the inlet of the entry port. Furthermore, at the inlet of the entry port, the converging channel can be taller than the inlet. Finally, in some embodiments, at least a portion of the converging channel can be at least twice as tall as the inlet of the entry port.
To even further support transport of a sample liquid from the entry port into the distal region of the assembly and thereby avoid spilling of the sample liquid from the entry port, in some embodiments, the assembly can comprise a hydrophobic material such that the contact angle between water and a surface of the assembly is between 90 and 120 degrees, more preferably between 90 and 110 degrees.
In certain embodiments, the reservoir of the assembly further comprises a second fin. In such embodiments, the second fin extends from the second lateral edge of the inlet towards the distal wall. Like the first fin, the second fin comprises a first surface and a second surface. In embodiments in which the reservoir comprises a second fin, instead of the second lateral wall further defining the converging channel as described above, the first surface of the second fin further defines the converging channel. Furthermore, the second surface of the second fin in part defines a second diverging channel. In embodiments in which the first diverging channel and the second diverging channel are not in fluidic communication with one another via a shared proximal portion of the reservoir, but rather the first diverging channel is in fluidic communication with a first proximal portion of the reservoir and the second diverging channel is in fluidic communication with a separate, second proximal portion of the reservoir, the second diverging channel is in fluidic communication with a second gas vent of the entry port. However, in alternative embodiments in which the first diverging channel and the second diverging channel are in fluidic communication with one another via a shared proximal portion of the reservoir, inclusion of a second gas vent in fluidic communication with the second diverging channel is optional. To neutralize forces between the converging channel and the first and second diverging channels at the distal region of the assembly, such that a sample liquid can concentrate at the distal region of the assembly, at a distal end of the second fin (i.e., the portion of the second fin that is closest in proximity to the distal wall of the reservoir), a width of the converging channel is substantially equivalent to, or less than, a width of the second diverging channel. Furthermore, a distance between the distal end of the second fin and the distal wall is substantially equivalent to, or less than, the width of the converging channel at the distal end of the second fin.
In embodiments in which the reservoir of the assembly comprises a second fin, in some embodiments, the second diverging channel is further defined by a second lateral wall of the reservoir. This second lateral wall extends between the proximal region of the assembly and the distal wall of the reservoir. Furthermore, in certain embodiments, the first fin and the second fin are located a substantially equivalent distance from a center point of the distal wall. In further embodiments, a length of the first fin is substantially equivalent to a length of the second fin. Additionally, like the first fin, in some embodiments, the second fin can increase in thickness as a distance from the entry port increases.
In certain embodiments of the disclosed assembly, the assembly further comprises a top wall. In embodiments in which the assembly comprises a top wall, the top wall extends between the proximal region of the assembly and the distal wall, and bounds, at least in part, the reservoir of the assembly. In embodiments in which the reservoir comprises a first fin, the top wall can contact the first fin, thereby preventing a sample liquid contained within the assembly from flowing over the first fin between the converging channel and the first diverging channel. However, in alternative embodiments, the assembly still functions as described herein when top wall does not contact the first fin. In further embodiments in which the assembly comprises a second fin, the top wall may also contact the second fin, thereby preventing a sample liquid contained within the assembly from flowing over the second fin between the converging channel and the second diverging channel. Similarly, in alternative embodiments, the assembly still functions as described herein when top wall does not contact the second fin. In some aspects, at least a portion of the top wall comprises a transparent viewing window that enables a user of the assembly to monitor a height of a sample liquid in the reservoir of the assembly.
In further embodiments of the disclosed assembly, the assembly further comprises a base. In embodiments in which the assembly comprises a base, the base extends between the proximal region of the assembly and the distal wall of the reservoir, and bounds, at least in part, the entry port and the reservoir of the assembly. The base can comprise a thin film. In some embodiments, the base further bounds a bottom edge of the inlet of the entry port and/or a bottom surface of the entry port.
In some embodiments, the assembly can further comprise an exit port, a cap, a gas conduit, and/or a pressurized gas source. In embodiments in which the assembly further comprises an exit port, the exit port is located at a distal region of the assembly. In embodiments in which the assembly further comprises a cap, the cap is configured to seal the entry port. In embodiments in which the assembly further comprises a gas conduit, the gas conduit is located at the proximal region of the assembly. In some embodiments, the gas conduit is in fluidic communication with the entry port. In alternative embodiments, the gas conduit is in fluidic communication with the reservoir of the assembly at the proximal region of the assembly. In embodiments in which the assembly further comprises a pressurized gas source, the pressurized gas source is in fluidic communication with the gas conduit, and is configured to supply a gas to the gas conduit. In alternative embodiments, the assembly does not comprise a pressurized gas source.
In one state of the assembly, the gas conduit and the exit port are closed and the cap is removed from the entry port such that the entry port is not sealed. In another state of the assembly, the cap is in place such that the entry port is sealed and the exit port and the gas conduit are open.
In another aspect, the disclosure provides a fluidic device that comprises, at least in part, an embodiment of the assembly described above that comprises a cap. In such embodiments, a top of the cap can be recessed from a surface of the fluidic device when the cap is in place over the entry port. Alternatively, the top of the cap can be flush with the surface of the fluidic device when the cap is in place over the entry port.
In another aspect, the disclosure provides a method for loading a sample liquid into an assembly. The method includes receiving an assembly according to one of the embodiments described above, and introducing a sample liquid into the entry port of the assembly. In certain embodiments, the sample liquid is introduced into the entry port via a pipette. In further embodiments, a volume of the reservoir can be about twice a volume of the introduced sample liquid. In embodiments in which the assembly comprises the cap, the gas conduit, and the exit port, the method further comprises removing the cap from the entry port such that the entry port is not sealed, and closing the gas conduit and the exit port prior to introduction of the sample liquid into the entry port of the assembly.
Upon introduction of the sample liquid into the entry port of the assembly, the sample liquid is drawn through the inlet of the entry port and into the converging channel. In some embodiments, the sample liquid is drawn through the inlet of the entry port into the converging channel at a rate such that the entry port does not overflow with the sample liquid. Upon entering the converging channel, the sample liquid is then drawn toward the distal region of the assembly, where the sample liquid contacts the distal wall. In embodiments in which the assembly comprises a transparent viewing window that is located above the reservoir, the method can further comprise the step of monitoring a height of the sample liquid within the reservoir via the transparent viewing window.
Upon entering the distal region of the assembly, the sample liquid flows into the diverging channel(s) of the assembly. Upon entry of the sample liquid into the diverging channel(s), the diverging channel(s) retard flow of the sample liquid in the diverging channel(s) toward the gas vent(s). Due to this retardation of flow of the sample liquid in the diverging channel(s), the sample liquid concentrates at the distal region of the assembly.
In embodiments of the disclosed method in which the assembly comprises the cap, the gas conduit, the pressurized gas source, and the exit port, the method further comprises placing the cap over the entry port such that the entry port is sealed, rotating the assembly such that a length of the converging channel is parallel to gravity, opening the exit port and the gas conduit, and supplying, with the pressurized gas source, via the gas conduit, a pressurized gas into the assembly.
In embodiments of the assembly in which the gas conduit is in fluidic communication with the entry port, the pressurized gas is supplied to the entry port of the assembly. Upon entry of the pressurized gas into the entry port, the pressurized gas travels into the converging channel via the inlet of the entry port and into the diverging channel(s) via the gas vent(s). Specifically, in embodiments in which the assembly comprises one or more diverging channels in fluidic communication with a shared proximal portion of the reservoir, and thus at least one gas vent in fluidic communication with the shared proximal portion of the reservoir, upon entry of the gas into the entry port, the gas travels into the one or more diverging channels via the at least one gas vent in fluidic communication with the shared proximal portion of the reservoir, and into the converging channel via the inlet. In alternative embodiments in which the assembly comprises multiple diverging channels, with one or more of the multiple diverging channels in fluidic communication with separate proximal portions of the reservoir, and thus at least one gas vent in fluidic communication with each separate proximal portion of the reservoir, upon entry of the gas into the entry port, the gas travels into the one or more diverging channels in fluidic communication with each separate proximal portion of the reservoir via the at least one gas vent in fluidic communication with each separate proximal portion of the reservoir, and into the converging channel via the inlet.
In alternative embodiments, the gas conduit is in fluidic communication with the converging channel of the assembly at a location proximal to the inlet of the entry port. In a preferred embodiment of this placement of the gas conduit, the gas conduit enters the converging channel from a top wall of the assembly. In such embodiments, a pressurized gas is supplied into the converging channel of the assembly via the opened gas conduit. Upon entry of the pressurized gas into the converging channel, the pressurized gas directly enters the converging channel and travels into the diverging channel(s) via the inlet of the entry port and the gas vent(s) of the entry port. Specifically, upon entry of the pressurized gas into the converging channel via the gas conduit, the gas directly enters the converging channel, and travels into one or more diverging channels of the assembly via the inlet, the entry port, and the gas vent(s) that are in fluidic communication with one or more proximal portions of the reservoir.
In further alternative embodiments of the assembly in which the gas conduit is in fluidic communication with a proximal portion of the reservoir, the gas is supplied to the proximal portion of the reservoir. Upon entry of the pressurized gas into the proximal portion of the reservoir, the pressurized gas travels into the into the diverging channel(s) via the fluidic connections between the diverging channel(s) and the proximal portion of the reservoir, and into the converging channel via the gas vent(s) and the inlet of the entry port. Specifically, in embodiments in which the assembly comprises one or more diverging channels that are in fluidic communication with a shared proximal portion of the reservoir, and thus at least one gas vent in fluidic communication with the shared proximal portion of the reservoir, upon entry of the gas into the shared proximal portion of the reservoir, the gas travels into the one or more diverging channels via the fluidic connection between the shared proximal portion of the reservoir and the one or more diverging channels, and into the converging channel via the at least one gas vent in fluidic communication with the shared proximal portion of the reservoir, the entry port, and the inlet of the entry port. In alternative embodiments in which the assembly comprises multiple diverging channels, with one or more of the multiple diverging channels in fluidic communication with separate proximal portions of the reservoir, and thus at least one gas vent in fluidic communication with each separate proximal portion of the reservoir, upon entry of the gas into the entry port, when the gas enters one of the separate proximal portions of the reservoir via the gas conduit, the gas travels into the one or more diverging channels in fluidic communication with the one separate proximal portion of the reservoir via the fluidic communication between the one separate proximal portion of the reservoir and the one or more diverging channels. Then, to travel into the one or more diverging channels in fluidic communication with the other separate proximal portion(s) of the reservoir, the gas travels into the entry port via the at least one gas vent in fluidic communication with the one separate proximal portion of the reservoir, into the other separate proximal portion(s) of the reservoir via the at least one gas vent in fluidic communication with each of the other separate proximal portion(s) of the reservoir, and into the one or more diverging channels in fluidic communication with the other separate proximal portion(s) of the reservoir via the fluidic connection(s) between the one or more diverging channels and the other separate proximal portion(s) of the reservoir. Finally, to travel into the converging channel, the gas travels through the inlet of the entry port into the converging channel.
Regardless of the path by which the gas enters the converging channel and the diverging channel(s), entry of the gas into the converging channel and the diverging channel(s) forces the sample liquid located in the converging channel and in the diverging channel(s) towards the open exit port. Upon reaching the open exit port, the sample liquid is transported out of the apparatus via the open exit port.
The present application is further understood when read in conjunction with the appended drawings. For the purpose of illustrating the subject matter, there are shown in the drawings exemplary embodiments of the subject matter; however, the presently disclosed subject matter is not limited to the specific systems, devices, and methods disclosed. In addition, the drawings are not necessarily drawn to scale. In the drawings:
Systems, devices, and methods for loading a sample liquid into an entry port of an assembly, and transferring the loaded sample liquid from the entry port into a reservoir of the assembly, while minimizing spilling of the sample liquid from the assembly, are provided herein. The devices disclosed herein include an entry port and a reservoir. The entry port is located at a proximal region of the device and comprises an inlet and a gas vent. The reservoir comprises a distal wall, a fin, and a continuous fluidic pathway. The distal wall is located at a distal region of the device. The fin extends from the inlet of the entry port towards the distal wall. The continuous fluidic pathway comprises a converging channel and a diverging channel. The converging channel is defined in part by a first surface of the fin, and is in fluidic communication with the inlet of the entry port. The first diverging channel is defined in part by a second surface of the fin, and is in fluidic communication with the gas vent of the entry port. At a distal end of the fin, a width of the converging channel is substantially equivalent to, or less than, a width of the first diverging channel, and a distance between the distal end of the fin and the distal wall is substantially equivalent to, or less than, the width of the converging channel at the distal end of the fin. In some embodiments, the methods disclosed herein include introducing a sample liquid into the entry port of the device, whereupon the sample liquid is drawn through the inlet of the entry port and into the converging channel of the assembly. When the sample liquid enters the converging channel, the sample liquid is drawn toward the distal region of the assembly. Once in the distal region of the assembly, the sample liquid flows into the first diverging channel. The dimensions of the first diverging channel retard the flow of the sample liquid further into the first diverging channel, thereby concentrating the sample liquid at the distal region of the assembly.
Before the disclosed embodiments are described in greater detail, it is to be understood that this disclosure is not limited to particular embodiments described, as such can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.
Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the present disclosure. The upper and lower limits of these smaller ranges can independently be included in the smaller ranges and are also encompassed within the present disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the present disclosure.
Below are examples of specific embodiments for carrying out the present invention. The examples are offered for illustrative purposes only, and are not intended to limit the scope of the present invention in any way. Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperatures, etc.), but some experimental error and deviation should, of course, be allowed for.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which these disclosed embodiments belong. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the disclosed embodiments, representative illustrative methods and materials are now described. Any recited method can be carried out in the order of events recited or in any other order which is logically possible.
It is noted that, as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise.
Included in the disclosure are systems, devices, and methods for loading a sample liquid into an entry port of an assembly, and transferring the loaded sample liquid from the entry port into a reservoir of the assembly, while minimizing spilling of the sample liquid from the assembly. Systems according to the subject embodiments include an assembly that comprises an entry port and a reservoir used in conjunction with one another to load and transport a sample liquid.
The assembly 100 depicted in
The entry port of the assembly is configured to receive a sample liquid. In some particular embodiments, the entry port is configured to receive a sample liquid from a pipette. The entry port comprises an inlet 141 and a gas vent 165. The inlet defines an opening of the entry port, and comprises a first lateral edge 142 and a second lateral edge 143. The gas vent defines another opening of the entry port. Both the inlet and the gas vent are discussed in further detail below.
The reservoir of the assembly comprises a distal wall 110, a fin 160, and a continuous fluidic pathway. The distal wall of the reservoir is located at the distal region of the assembly.
The fin extends from a lateral edge of the inlet of the entry port towards the distal wall. The fin and the lateral edge of the inlet of the entry port are contiguous such that there is no gap between the entry port and the fin. The fin comprises a first surface 161 and a second surface 162. As shown in
As shown in
The continuous fluidic pathway of the reservoir comprises a converging channel 150 and a diverging channel 164. The converging channel of the continuous fluidic pathway is in fluidic communication with the inlet of the entry port, and is defined in part by the second surface of the fin. Because there is no gap between the entry port and the fin as described above, a sample liquid flowing out of the entry port via the inlet flows directly into the converging channel.
As depicted in
The diverging channel of the continuous fluidic pathway is defined in part by the first surface of the fin. The diverging channel is in fluidic communication with the gas vent of the entry port.
As depicted in
At the distal end of the fin, the width of the converging channel is substantially equivalent, or less than, to the width of the diverging channel. Furthermore, the distance between the distal end of the fin and the distal wall is substantially equivalent to, or less than, the width of the converging channel at the distal end of the fin. As used herein, values being “substantially equivalent” means that the values differ by no more than +/−25%. The substantial equivalence of the width of the converging channel and the width of the diverging channel at the distal end of the fin neutralizes the forces between the converging channel and the diverging channel at the distal region of the assembly, such that a sample liquid can concentrate at the distal region of the assembly, as discussed in further detail below.
As noted above, a distance exists between the distal wall of the reservoir and the distal end of the fin. This distance between the distal wall and the distal end of the fin in part defines a distal portion of the reservoir that is not a part of the converging channel or the diverging channel. This distal portion of the reservoir fluidically connects the converging channel and the diverging channel, which are located on opposite sides of the fin. In other words, a sample liquid can flow from the converging channel around the distal end of the fin and into the diverging channel via a distal portion of the reservoir.
In addition to the distal portion of the reservoir, the reservoir typically also comprises a proximal portion. The proximal portion of the reservoir begins where the diverging channel ends at the proximal region of the assembly. Specifically, the proximal portion of the reservoir begins where the diverging channel ceases to diverge, and extends towards the proximal end of the assembly. The proximal portion of the reservoir is not a part of the diverging channel, but rather is in fluidic communication with the diverging channel. As seen in
As briefly discussed above, the diverging channel is in fluidic communication with the gas vent of the entry port. In some embodiments, this fluidic communication between the diverging channel and the gas vent is direct such that the diverging channel and the gas vent are directly connected. In alternative embodiments, this fluidic communication between the diverging channel and the gas vent is indirect such that the diverging channel and the gas vent are indirectly connected via a proximal portion of the reservoir. More specifically, in embodiments in which the diverging channel and the gas vent are in indirect fluidic communication, the gas vent may be directly connected to the proximal portion of the reservoir, which is in turn connected to the diverging channel. Embodiments in which a gas vent is in direct and in indirect fluidic communication with a diverging channel are discussed in further detail below.
In some embodiments, such as the embodiment in
In some embodiments, the assembly further comprises a second lateral wall 176 that extends from the proximal region of the assembly to the distal wall, such that the second lateral wall contacts the distal wall. In embodiments in which the assembly comprises a single converging channel, a single fin and a single diverging channel, such as the embodiment depicted in
In some embodiments, such as the embodiment depicted in
Turning first to the entry port of the assembly depicted in
Turning next to the reservoir of the assembly of
In some embodiments, the first fin and the second fin are located a substantially equivalent distance from a center point 111 of the distal wall. In further embodiments, a length of the first fin is substantially equivalent to a length of the second fin. As used herein, values being “substantially equivalent” means that the values differ by no more than +/−25%.
Rather than the second lateral wall defining the converging channel as described above with regard to
As shown in
As depicted in
As discussed above with regard to
As also discussed above with regard to
Embodiments in which a shared proximal portion of the reservoir is in fluidic communication with the two diverging channels are depicted in
In embodiments in which a shared proximal portion of the reservoir is in fluidic communication with multiple diverging channels (e.g., the first and second diverging channels), inclusion of more than one gas vent in fluidic communication with the multiple diverging channels is optional because gas can travel into and out of any of the multiple diverging channels via the shared proximal portion of the reservoir that in fluidic communication with a single gas vent. For example, while the embodiments of the assembly depicted in
In addition to the optional inclusion of more than one gas vent in the assembly of
In alternative embodiments of the assembly, such as the embodiment depicted in
In embodiments in which one or more of multiple diverging channels are in fluidic communication with separate proximal portions of the reservoir, at least one gas vent is in fluidic communication with at least one diverging channel of the one or more diverging channels in fluidic communication with each separate proximal portion of the reservoir. In simpler terms, at least one gas vent is in fluidic communication with each separate proximal portion of the reservoir. This placement of gas vents enables gas to travel into and out of each diverging channel despite the separation of the proximal portions of the reservoir. For example, in the embodiment of the assembly depicted in
The at least one gas vent in fluidic communication with the at least one diverging channel of the one or more diverging channels in fluidic communication with each separate proximal portion of the reservoir, can either be in direct or indirect fluidic communication the at least one diverging channel because the one or more diverging channels are all in fluidic communication with the separate proximal portion of the reservoir. For example, in
Turning finally to the lateral wall of the reservoir of
First, as briefly discussed above, the two diverging channels and two gas vents of
Turning to the additional, optional features of the assembly of
The exit port is located at the distal region 202 of the assembly. For example, as shown in
In addition to the exit port, the assembly depicted in
The gas conduit is located at the proximal region 201 of the assembly. Specifically, in some embodiments, such as the embodiment of
In alternative embodiments, such as the embodiment discussed in further detail below with regard to
In even further embodiments not depicted herein, the gas conduit can be located at the proximal region of the assembly such that the gas conduit is in fluidic communication with the converging channel of the assembly at a location proximal to the inlet of the entry port. In a preferred embodiment of this placement of the gas conduit, the gas conduit enters the converging channel from a top wall of the assembly (described in further detail below with regard to
In some embodiments, such as the embodiment depicted in
In some implementations, such as illustrated in
Specifically, as briefly discussed above, and as seen in
First, the assembly depicted in
In some embodiments, such as the embodiment depicted in
In certain embodiments, the top wall contacts the fin, thereby preventing a sample liquid contained within the assembly from flowing over the fin between a converging channel and diverging channel. In further embodiments in which the assembly comprises more than one fin, the top wall may also contact each fin, or contact a subset of the additional fin(s). However, in alternative embodiments, as discussed in further detail below, the assembly still functions as described herein when top wall does not contact one of more of the fins.
In some embodiments of the assembly, such as those shown in
In addition to the top wall, the assembly depicted in
As discussed above, in embodiments in which the assembly comprises a single fin and a single diverging channel, the reservoir of the assembly comprises the distal wall, the first fin, and the continuous fluidic pathway, which in turn comprises the converging channel and the first diverging channel. Therefore, in embodiments in which the assembly comprises a single fin and a single diverging channel, the base bounds, at least in part, the distal wall, the first fin, the converging channel, and the first diverging channel. On the other hand, in embodiments in which the assembly comprises a two fins and two diverging channels, the reservoir of the assembly comprises the distal wall, the first fin, the second fin, and the continuous fluidic pathway, which in turn comprises the converging channel, the first diverging channel, and the second diverging channel. Therefore, in embodiments in which the assembly comprises two fins and two diverging channels, the base bounds, at least in part, the distal wall, the first fin, the second fin, the converging channel, the first diverging channel, and the second diverging channel.
In some embodiments, such as the embodiment depicted in
In addition to depicting these additional optional features of the assembly,
As shown in
However, this preferred embodiment of the assembly in which the height of a reservoir is lower at the inlet relative to the distal portion of the reservoir poses problems to the functioning of an assembly that lacks the converging and diverging channels of the invention. Specifically, when a sample liquid is loaded into the entry port of an assembly that lacks the converging and diverging channels of the invention, and in which the height of the reservoir is lower at the inlet relative to the distal portion of the reservoir, the loaded sample liquid may quickly fill the entry port, and in some cases overflow and spill from the entry port due to this decreased height, and therefore a decreased volume, of the proximal end of the reservoir.
To avoid spilling during loading of the sample liquid, and to maximize the volume that can be loaded into an assembly of limited dimensions, the fluidic pathways (e.g., the converging channel and the diverging channel(s)) of the assembly are configured such that the width of each fluidic pathway decreases towards the distal portion of the reservoir. As a result of this decreasing width of the fluidic pathways distally of the inlet, when a sample liquid is loaded into the entry port of the assembly, the sample liquid is quickly drawn from the inlet of the entry port toward the distal portion of the reservoir by the combined forces of capillary action and gravity. Therefore, despite the decreased height and the decreased volume of the reservoir at the proximal end, the entry port does not overflow with the sample liquid.
In one embodiment of the assembly, the assembly comprises an entry port and a continuous fluidic pathway. As discussed above, the entry port is located at a proximal region of the assembly, and comprises an inlet and a gas vent. Both the inlet and the gas vent define openings within the entry port. A continuous fluidic pathway extends from the inlet of the entry port to the gas vent of the entry port. More specifically, a first end of the continuous fluidic pathway is in fluidic communication with the inlet of the entry port and a second end of the continuous fluidic pathway is in fluidic communication with the gas vent of the entry port. The continuous fluidic pathway progressively narrows from the inlet toward a position distal to the inlet. The continuous fluidic pathway also progressively narrows from the gas vent towards the position distal to the inlet. Optionally, this embodiment of the assembly comprises a cap to seal the entry port, and thereby create a closed system.
In addition to the embodiment discussed above in which the reservoir is taller at the distal portion of the reservoir than at the inlet of the entry port, in a further preferred embodiment, at the inlet of the entry port, the converging channel is taller than the inlet. In an even further preferred embodiment, at least a portion of the converging channel is at least twice as tall as the inlet of the entry port. Finally, in an even further preferred embodiment, the width of the converging channel at the inlet is less than the height of the inlet.
In many existing microfluidic devices, the speed at which a sample liquid can be drawn into the device is increased by increasing the wettability of the device, by manufacturing the device to comprise hydrophilic surfaces. For example, in some embodiments, the sample loading device may be manufactured to comprise a hydrophilic material. In further embodiments, surfaces of the sample loading device may be treated with a hydrophilic treatment. Such treatment is unnecessary for the present assemblies and methods to function.
Despite this tendency in the field to manufacture sample loading devices to comprise hydrophilic surfaces, in some embodiments, the assembly disclosed herein comprises a hydrophobic material. For example, in some embodiments, the assembly can comprise one or more thermoplastic materials. Such materials can include acrylonitrile butadiene styrene (ABS), acrylic, such as poly(methyl methacrylate) (PMMA), polyoxymethylene (POM), also known as acetal, polyacetal and polyformaldehyde, aliphatic or semi-aromatic polyamide (PA), polyethylene (PE), polypropylene (PP), polyetheretherketone (PEEK), cyclic olefin copolymer (COC), cyclic olefin polymer (COP), polycarbonate (PC), and blends thereof. In embodiments in which the assembly comprises a hydrophobic material, the contact angle between water and a surface of the assembly may be between 90 and 120 degrees. Specifically, in embodiments in which the assembly comprises a hydrophobic material, the contact angle between water and a surface of the reservoir of the assembly (e.g., the converging channel, the fin(s), the diverging channel(s), the base, the top wall, the distal wall, the lateral wall(s), the transparent viewing window, etc.) may be between 90 and 120 degrees. In such embodiments, despite the hydrophobicity of the assembly, sample liquid can still be loaded into the assembly and drawn toward the distal region of the assembly without spilling of the sample liquid.
While not absolutely necessary for operation of the assemblies described herein, in certain implementations, the inlet can comprise a hydrophilic wick to prevent the inlet from acting as a capillary stop. In one embodiment, the wick is made of a hydrophilic non-porous material such as PVDF (polyvinylidenefluoride), PVA(polyvinyl aetate), PVOH (polyvinyl alcohol), PPO (polyphenyleneoxide), PEI (polyethyleneimine), paper, cellulose, or Nylon. Preferably, the wick is approximately as wide as the center channel, and ideally runs from the sample entry port to the point where it is barely sticking into the inlet. This arrangement of the wick will shuttle fluid along the length of the sample entry port toward and through the inlet at which point the fluid is drawn toward the distal wall by action of the converging channel. Such an arrangement would permit a user to drop fluid onto the wick rather than requiring the user to properly position the pipette tip at the inlet.
In another embodiment comprising a hydrophilic wick at the inlet, a hydrophilic material, such as PVDF, PVA, PPO, PEI, agarose, PLA (polylactic acid), PEG (polyethylene glycol), PEO (polyethylene oxide) or Nylon, is layered onto the assembly such that the hydrophilic material bridges the gap from the sample input well to the beginning of the converging section of the sample input port. The hydrophilic material can be drop cast to form this layer by dissolving the hydrophilic material in an appropriate solvent, i.e., any solvent that can dissolve the polymer but not hydrophobic material of the main assembly body. Once dissolved, a drop is deposited at the inlet to form a layer of the hydrophilic material upon removal, e.g. by evaporation, of the solvent. Such an embodiment similarly would permit the user to drop fluid anywhere on the sample entry port rather than positioning a pipette over the inlet to the reservoir. In certain implementations, this layer of hydrophilic material may be dissolvable is the typical sample solution. Exemplary dissolvable hydrophilic materials include sugars or gating films. Presence of the dissolvable hydrophilic material at the start of filling would enhance flow of the sample from the entry port through the inlet. However after filling is complete, the hydrophilic material has been dissolved and removed by the flow of the sample, reinstituting the ability of the inlet to act as a capillary stop preventing loaded fluid from exiting the reservoir after filling, thus avoiding an accidental spill during handling of the filled assembly.
When the cap is in place such that the entry port is capped, the cap seals the entry port such that fluid (i.e., gas and liquid) is prevented from exiting the assembly via the entry port, and such that fluid is prevented from entering the entry port from outside of the assembly. However, note that capping the entry port does not prevent fluid from traveling into and out of the entry port from within the assembly. Specifically, a described above, the entry port comprises an inlet 441 and at least one gas vent (e.g., a first gas vent 465 and a second gas vent 475). Therefore, the cap is configured to seal the at least one gas vent of the entry port such that fluid (such as gas) cannot exit the assembly via the at least one gas vent. However, fluid from the entry port can travel into and out of one or more diverging channels (e.g., a first diverging channel 464 and a second diverging channel 474) via the at least one gas vent and in some embodiments, one or more proximal portions of the reservoir. Similarly, fluid from the entry port can travel into and out of the converging channel 450 via the inlet of the entry port.
When the cap is not closed over the entry port such that the entry port is not capped, the entry port is unsealed, permitting fluid to enter or exit the assembly via the entry port. Specifically, when the cap is separate from the entry port such that the entry port is not sealed, fluid (e.g., gas) from the one or more diverging channels is able to exit the entry port via the at least one gas vent. Fluid (e.g., sample liquid) can also be loaded in to the entry port when the cap is removed from the entry port such that the entry port is not sealed.
As briefly discussed above with regard to
Therefore, in certain embodiments, the novel devices described herein are configured such that the first location of the fluidic device, e.g., the entry port, at which the sample liquid is loaded into the fluidic device, is flush, or even recessed, with respect to the rest of the fluidic device. By configuring the fluidic devices such that the first location of the fluidic device is flush or recessed from the rest of the fluidic device, the fluidic device can easily be incorporated into a larger consumable device, such as a lab-on-a-chip device.
In embodiments of existing fluidic devices in which the first location of the fluidic device is flush or recessed from the rest of the fluidic device, when a sample liquid is loaded into the fluidic device at the first location, the loaded sample liquid may overflow and spill from the fluidic device. Not only does this spilling of the sample liquid contaminate the environment surrounding the fluidic device, but in embodiments in which the sample liquid comprises a biologically hazardous material, spilling of the sample liquid also poses a safety concern. Furthermore, as discussed above, spilling of the sample liquid results in loss of the sample liquid, which can be detrimental in embodiments in which a precise volume of the sample liquid is needed to generate reliable assay results. To combat these problems and avoid spilling of the sample liquid from the fluidic device, the novel fluidic devices described herein are further configured draw the sample liquid from the first location of the fluidic device to the alternative location of the fluidic device at a velocity such that such that the fluidic device does not overflow with the sample liquid. This improves upon the safety and ease-of-use of the fluidic device, as well as improves upon the reliability of assay results generated by the fluidic device.
As shown in the legend at the bottom left-hand corner of
With the cap separated from the entry port, and both the gas conduit and the exit port closed, the sample liquid is introduced into the entry port of the assembly. In some embodiments, the sample liquid can be introduced in to the entry port of the assembly via a pipette.
In some embodiments, a volume of the reservoir of the assembly is about twice a volume of the sample liquid that is introduced into the entry port. As used herein, when used to modify a numerical value (e.g., twice the volume of the sample liquid), the term “about” means that the numerical value differs by no more than +/−50%.
Upon introduction of the sample liquid into the entry port of the assembly, the sample liquid is drawn through the inlet 541 of the entry port, and into the converging channel 550. Once in the converging channel, the sample liquid is then drawn toward the distal region 502 of the assembly via the converging channel, such that the sample liquid contacts the distal wall 510. In other words, the sample liquid is drawn toward the distal portion of the reservoir of the reservoir.
This transport of the sample liquid from the entry port, through the inlet into the converging channel, and finally into the distal portion of the reservoir, is effected through both gravitational forces and capillary action. Specifically, gravity disperses the sample liquid throughout the continuous fluidic pathway such that, independent of any other force, e.g. capillary action, the sample liquid would be distributed throughout the continuous fluidic pathway in a uniformly level (e.g., flat) layer. Capillary action acts within the converging channel to draw the sample liquid through the converging channel in the direction in which the converging channel narrows. Therefore, a combination of gravity and capillary action draws the sample liquid act on the sample liquid into the distal portion of the reservoir.
As briefly discussed above, by quickly drawing the sample liquid into the distal region of the assembly via the converging channel, overflow of the sample liquid from the entry port is avoided. Specifically, upon introduction of the sample liquid into the entry port of the assembly, the sample liquid is drawn through the inlet of the entry port and into the converging channel at a velocity such that the entry port does not overflow with the sample liquid. As discussed above, this transport of the sample liquid is accomplished as a result of the narrowing of the converging channel in the direction of the distal wall of the reservoir.
As the distal portion of the continuous fluidic pathway fills with the sample liquid from the converging channel, the force of gravity continues to disperse the sample liquid into the first diverging channel towards the first gas vent. In embodiments in which the assembly also comprises a second diverging channel, such as the embodiment depicted in
However, this dispersion of the sample liquid into the diverging channel(s) towards the gas vent(s) is retarded by the diverging channel(s). Specifically, as discussed above, the diverging channel(s) widen as a distance from the distal wall increases. In other words, as the distance from the distal wall increases, the widths of the diverging channel(s) increase. As a result of these increasing widths of the diverging channel(s), advance of the sample liquid in the diverging channel(s) towards the gas vent(s) is retarded. Due to this retardation of flow of the sample liquid from the distal portion of the reservoir into the diverging channel(s)—in addition to the forces of gravity and capillary action in the converging channel urging the sample liquid into the distal portion of the reservoir—the sample liquid concentrates at the distal portion of the reservoir.
As discussed above, during the first step of the method depicted in
In embodiments in which the assembly comprises a cap, such as the embodiment depicted in
After the entry port has been sealed with the cap, the assembly is rotated such that a length of the converging channel of the assembly is parallel to gravity, and such that the sample liquid contained within the assembly travels towards the distal region of the assembly as a result of this rotation.
In embodiments in which the assembly comprises a gas conduit and an exit port, following rotation of the assembly as described above, both the exit port and the gas conduit are opened such that fluid is able to enter and exit the assembly via the gas conduit and the exit port. In embodiments in which the assembly comprises a pressurized gas source connected to the gas conduit, the pressurized gas source supplies pressurized gas to the assembly via the opened gas conduit. In alternative embodiments however, the assembly does not comprise a pressurized gas source attached to the gas conduit. In such embodiments, a pressurized gas source can be attached to the gas conduit, and then a pressurized gas may be supplied to the assembly by the pressurized gas source, via the gas conduit.
As discussed above, in some embodiments, the gas conduit is in fluidic communication with the entry port of the assembly. In such embodiments, the pressurized gas source supplies the pressurized gas into the entry port of the assembly via the opened gas conduit. Upon entry of the pressurized gas into the entry port, the pressurized gas travels into the converging channel via the inlet of the entry port and into the diverging channel(s) via the gas vent(s). Specifically, in embodiments in which the assembly comprises one or more diverging channels in fluidic communication with a shared proximal portion of the reservoir, and thus at least one gas vent in fluidic communication with the shared proximal portion of the reservoir, upon entry of the gas into the entry port, the gas travels into the one or more diverging channels via the at least one gas vent in fluidic communication with the shared proximal portion of the reservoir, and into the converging channel via the inlet. In alternative embodiments, in which the assembly comprises multiple diverging channels, with one or more of the multiple diverging channels in fluidic communication with separate proximal portions of the reservoir, and thus at least one gas vent in fluidic communication with each separate proximal portion of the reservoir, upon entry of the gas into the entry port, the gas travels into the one or more diverging channels in fluidic communication with each separate proximal portion of the reservoir via the at least one gas vent in fluidic communication with each separate proximal portion of the reservoir, and into the converging channel via the inlet.
In alternative embodiments, the gas conduit is in fluidic communication with the converging channel of the assembly at a location proximal to the inlet of the entry port. In a preferred embodiment of this placement of the gas conduit, the gas conduit enters the converging channel from a top wall of the assembly. In such embodiments, the pressurized gas source supplies the pressurized gas into the converging channel of the assembly via the opened gas conduit. Upon entry of the pressurized gas into the converging channel, the pressurized gas directly enters the converging channel and travels into the diverging channel(s) via the inlet of the entry port and the gas vent(s) of the entry port. Specifically, upon entry of the pressurized gas into the converging channel via the gas conduit, the gas directly enters the converging channel, and travels into one or more diverging channels of the assembly via the inlet, the entry port, and the gas vent(s) that are in fluidic communication with one or more proximal portions of the reservoir.
In another alternative embodiment, the gas conduit is in fluidic communication with a proximal portion of the reservoir of the assembly. In such embodiments, the pressurized gas source supplies the pressurized gas into the proximal portion of the reservoir via the opened gas conduit. Upon entry of the pressurized gas into the proximal portion of the reservoir, the pressurized gas travels into the into the diverging channel(s) via the fluidic connections between the diverging channel(s) and the proximal portion of the reservoir, and into the converging channel via the gas vent(s) and the inlet of the entry port. Specifically, in embodiments in which the assembly comprises one or more diverging channels that are in fluidic communication with a shared proximal portion of the reservoir, and thus at least one gas vent in fluidic communication with the shared proximal portion of the reservoir, upon entry of the gas into the shared proximal portion of the reservoir, the gas travels into the one or more diverging channels via the fluidic connection between the shared proximal portion of the reservoir and the one or more diverging channels, and into the converging channel via the at least one gas vent in fluidic communication with the shared proximal portion of the reservoir, the entry port, and the inlet of the entry port. In alternative embodiments in which the assembly comprises multiple diverging channels, with one or more of the multiple diverging channels in fluidic communication with separate proximal portions of the reservoir, and thus at least one gas vent in fluidic communication with each separate proximal portion of the reservoir, upon entry of the gas into the entry port, when the gas enters one of the separate proximal portions of the reservoir via the gas conduit, the gas travels into the one or more diverging channels in fluidic communication with the one separate proximal portion of the reservoir via the fluidic communication between the one separate proximal portion of the reservoir and the one or more diverging channels. Then, to travel into the one or more diverging channels in fluidic communication with the other separate proximal portion(s) of the reservoir, the gas travels into the entry port via the at least one gas vent in fluidic communication with the one separate proximal portion of the reservoir, into the other separate proximal portion(s) of the reservoir via the at least one gas vent in fluidic communication with each of the other separate proximal portion(s) of the reservoir, and into the one or more diverging channels in fluidic communication with the other separate proximal portion(s) of the reservoir via the fluidic connection(s) between the one or more diverging channels and the other separate proximal portion(s) of the reservoir. Finally, to travel into the converging channel, the gas travels through the inlet of the entry port into the converging channel.
Regardless of the path by which the pressurized gas enters the converging channel and the diverging channel(s), entry of the pressurized gas into the converging channel and the diverging channel(s) forces the sample liquid located in the converging channel and in the diverging channel(s) towards the open exit port. Upon reaching the open exit port, the sample liquid is transported out of the reservoir via the open exit port.
As briefly mentioned above, in embodiments in which the assembly comprises a top wall, the top wall may or may not contact one or more of the fins of the assembly. For example, in some embodiments, there may be a gap of space between one of more of the fins and the top wall. However, the positioning of the fins with respect to the top wall does not affect functioning of the assembly. More specifically, in embodiments of the assembly in which the top wall does not contact one or more fins of the assembly, loading of the assembly with the sample liquid and evacuation of the sample liquid from the reservoir of the assembly occurs normally as described above.
As discussed above, in some embodiments, a transparent viewing window 621 is located above the reservoir of the assembly. In such embodiments, throughout the evacuation of the sample liquid from the assembly, a height of the sample liquid within the reservoir can be monitored via the transparent viewing window. By monitoring the height of the sample liquid in the reservoir, success of the evacuation of the sample liquid from the assembly can be determined by a user of the assembly.
As seen in
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