Patent Publication Number: US-10779757-B2

Title: Devices, systems and methods for gravity-enhanced microfluidic collection, handling and transferring of fluids

Description:
CROSS-REFERENCE TO RELATED APPLICATION(S) 
     This application claims priority to U.S. Provisional Application No. 62/032,266 filed Aug. 1, 2014 and entitled “Gravity-Enhanced Microfluidic Devices and Methods for Handling and Transferring Fluids,” and U.S. Provisional Application No. 62/101,784 filed Jan. 9, 2015 and entitled “Devices, Systems &amp; Methods for Gravity-Enhanced Microfluidic Collection, Handling And Transferring Of Fluids,” which are hereby incorporated by reference in their entirety under 35 U.S.C. § 119(e). 
    
    
     FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     This invention was made with government support under Contract # W31P4Q14C0006 awarded by DARPA. The government has certain rights in the invention. 
    
    
     TECHNICAL FIELD 
     The disclosed technology relates generally to the collection of bodily fluids, and in particular, to the devices, methods, and design principles allowing the collection of bodily fluids into a receptacle and, in certain embodiments, the process of acting on the fluid being collected with the utilization of gravity to add functionality. This has implications not only for active fluid collection, but also on downstream processing of the receptacle, including its presentation to equipment and processes. 
     BACKGROUND 
     Devices, systems and methods to collect bodily fluids are necessary devices for the growing field of personalized medicine. As point-of-care devices continue to improve, an often overlooked area lies within the collection of samples from untrained users. Currently, biological samples are most commonly obtained via either simple-to-use methods or devices, as with generic lancing devices, or trained personnel, as with phlebotomy venipunctures. In order to transfer the bodily fluid to a container, receptacle, or an analysis device, multiple steps are required that are time consuming and/or cumbersome. To circumvent these problems, there is a need for devices that are able to collect samples in a simple manner and have an integrated fluidic transfer to a container or receptacle that houses the samples. 
     Thus, there is a need in the art for improved microfluidic devices that utilize gravity and capillary forces for fluid handling and transfer, and related systems and methods. 
     BRIEF SUMMARY 
     Discussed herein are various embodiments of the collection device, as well as associated systems and methods for its use. For brevity, these embodiments may be described in relation to a “collector,” though that is not intended to limit the scope of the disclosure in any way. Further, the discussion of microfluidic channels may comprise open and closed channels, as well as channels featuring both open and closed portions. 
     In Example 1, microfluidic collection system for drawing blood from a subject comprising a collector further comprising a housing, at least one collection site, a microfluidic network further comprising at least one microfluidic channel disposed within the housing, and at least one outflow channel in fluidic communication with the microfluidic network, and at least one reservoir in fluidic communication with the at least one collection site by way of the outflow channel, wherein the system is configured to be placed on a subject&#39;s skin to draw blood, and the at least one microfluidic network is configured to promote the flow of fluids from the collection site to the at least one outflow channel. 
     In Example 2, the system of Example 1, further comprising an actuator configured to facilitate the puncture of skin. 
     In Example 3, the system of Example 1, wherein the at least one microfluidic channel further comprises a microfluidic channel geometry and a contact angle, and further wherein the at least one microfluidic channel is configured to promote the flow of fluids by at least one of capillary action and gravitational force. 
     In Example 4, the system of Example 3, wherein the collector and at least one microfluidic channel is configured to have a flow position and a stop position. 
     In Example 5, the system of Example 3, further comprising at least one open microfluidic channel. 
     In Example 6, the system of Example 3, further comprising at least one open microfluidic channel and at least one closed microfluidic channel. 
     In Example 7, the system of Example 3, wherein the microfluidic network further comprises at least one ramp. 
     In Example 8, the system of Example 3, wherein the microfluidic network further comprises at least one surface tension valve. 
     In Example 9, the system of Example 8, wherein the surface tension valve is configured to regulate the flow of fluids through the microfluidic network based on the orientation of the microfluidic network. 
     In Example 10, the system of Example 3, further comprising a coupling portion. 
     In Example 11, the system of Example 10, wherein the reservoir is detachable, and the coupling portion is further configured to receive a detachable reservoir. 
     In Example 12, gravity-enhanced collection system comprising a collector, further comprising a housing, a microfluidic network, further comprising at least one microfluidic channel disposed within the housing, at least one collection site disposed within the housing, at least one outflow channel, and at least one reservoir, wherein the at least one collection site is in microfluidic communication with the outflow channel by way of the microfluidic network so as to promote the flow of fluid to the reservoir by way of the outflow channel into the reservoir. 
     In Example 13, the system of Example 12, wherein the device is configured to use gravity to enhance fluid collection. 
     In Example 14, the system of Example 13, wherein the reservoir is a detachable reservoir. 
     In Example 15, the system of Example 13, wherein the outflow channel is configured to prevent backflow. 
     In Example 16, the system of Example 13, wherein the at least one microfluidic channel further comprises an open microfluidic channel and a closed microfluidic channel in fluidic communication with one another. 
     In Example 17, the system of claim  16  wherein the open microfluidic channel and closed microfluidic channels are in fluidic communication with one another. 
     In Example 18, the system of claim  16  further comprising a ramp. In certain Examples, this ramp may comprise an open microfluidic channel with at least one wetted surface defining a wetted perimeter length, wherein the wetted surface contacts a fluid flowing through the channel at a contact angle, and at least one free surface comprising an open air-liquid interface defining a free perimeter length, wherein the ratio of the free perimeter length to the wetted perimeter length is less than the cosine of the contact angle, thereby enabling spontaneous capillary flow. 
     In Example 19, the system of channel  15 , wherein the at least one microfluidic channel is capable of timed fluid delivery. 
     In Example 20, a method of drawing blood from a subject, comprising providing a blood collection device, comprising a housing, a microfluidic network further comprising at least one microfluidic channel disposed within the housing and at least one collection site, at least one outflow channel in fluidic communication with the microfluidic network, and at least one reservoir in fluidic communication with the at least one collection site by way of the network and outflow channel, placing the fluid connection device on the skin of the subject, puncturing the subject&#39;s skin so as to pool fluid, collecting pooling fluid from the skin and transporting it to the reservoir by way of the microfluidic network. 
     While multiple embodiments are disclosed, still other embodiments of the disclosure will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the disclosed apparatus, systems and methods. As will be realized, the disclosed apparatus, systems and methods are capable of modifications in various obvious aspects, all without departing from the spirit and scope of the disclosure. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  is a perspective view of the collector, according to an exemplary embodiment. 
         FIG. 1B  is a perspective view of the embodiment of  FIG. 1A , applied to the skin of a subject. 
         FIG. 1C  is a further perspective view of the embodiment of  FIG. 1A , wherein the reservoir is being removed. 
         FIG. 1D  is an exploded perspective view of one embodiment of the collector showing the base, actuator and lumen. 
         FIG. 1E  is perspective schematic of a microfluidic channel of an exemplary embodiment of the collector comprising two regions, a capillary-dominant region and a gravity-dominant region. 
         FIG. 1F  depicts the embodiment of  FIG. 1D , wherein the fluid is in the gravity-dominant region. 
         FIG. 1G  is the distance traveled by fluid in channels of specific characteristics. 
         FIG. 1H  is the distance traveled by fluid in a variety of channel designs. 
         FIG. 2A  depicts a top-down cross-sectional view of the collector, according to one embodiment. 
         FIG. 2B  depicts a top-down cross-sectional view of the collector, according to an alternate embodiment. 
         FIG. 2C  depicts a side view of the collector, according to an exemplary embodiment. 
         FIG. 2D  is a side view of the collector of  FIG. 2C  from an alternate angle. 
         FIG. 2E  is a side view of a collector having multiple reservoirs, according to an exemplary embodiment 
         FIG. 2F  is a side view of the collector of  FIG. 2E  from an alternate angle. 
         FIG. 3A  is a top-down cross-sectional view of the collector, according to one embodiment. 
         FIG. 3B  is a side view of the collector of  FIG. 3A . 
         FIG. 3C  is a side view of the collector of  FIG. 3A  from an alternate angle. 
         FIG. 3D  is a side view of a reservoir and outflow channel depicting a fluidic bridge, according to an exemplary embodiment. 
         FIG. 4A  depicts a top-down cross-sectional view of the collector, according to one embodiment. 
         FIG. 4B  depicts a top-down cross-sectional view of the collector, according to an alternate embodiment. 
         FIG. 4C  depicts a top-down cross-sectional view of the collector, according to an alternate embodiment. 
         FIG. 4D  depicts a top-down cross-sectional view of the collector, according to an alternate embodiment. 
         FIG. 5A  is a perspective view of the collector, according to an exemplary embodiment. 
         FIG. 5B  depicts a top-down cross-sectional view of the collector of  FIG. 5A , showing fitting and reservoir connection. 
         FIG. 5C  depicts a top-down cross-sectional view of the collector of  FIG. 5A , showing fitting and reservoir connection, wherein the reservoir is removed. 
         FIG. 5D  is a cutaway perspective view of the collector, according to an exemplary embodiment. 
         FIG. 5E  is a cross-sectional side view of the outflow channel and reservoir, according to an exemplary embodiment. 
         FIG. 6A  is a detailed perspective cross-sectional view of an outflow channel and reservoir, according to an exemplary embodiment. 
         FIG. 6B  is a perspective view of an open microfluidic channel which satisfies the SCF relationship and can serve as a ramp in certain embodiments. 
         FIG. 6C  is a perspective view of the channel of  FIG. 6B , further comprising fluid. 
         FIG. 7A  is a cross-sectional view of a surface tension valve in a closed position, according to an exemplary embodiment. 
         FIG. 7B  is a cross-sectional view of the valve of  7 A in an open position. 
         FIG. 7C  is a cross-sectional view of an alternative embodiment of a valve and channel configuration in the collector. 
         FIG. 7D  is a cross-sectional view of another alternative embodiment of a valve and channel configuration in the collector. 
         FIG. 8  is a further cross-sectional view of another alternative embodiment of a surface tension valve and channel configuration in the collector. 
         FIG. 9A  is a cross-sectional side view of an exemplary embodiment of an outflow channel in the reservoir. 
         FIG. 9B  depicts the channel and reservoir of  9 A in a horizontal position. 
         FIG. 9C  is a cross-sectional side view of an alternative exemplary embodiment of an outflow channel in the reservoir. 
         FIG. 9D  depicts the channel and reservoir of  9 C in a horizontal position. 
         FIG. 10  depicts a perspective cross-sectional view of a collection well, according to an exemplary embodiment. 
         FIG. 11  depicts a cross-sectional view of fluid flow through a channel having defects according to an exemplary embodiment. 
         FIG. 12A  depicts a top view of one embodiment of microchannels comprising surface tension guides, wherein gravity assists with the direction of flow. 
         FIG. 12B  depicts a top view of the embodiment of  FIG. 12A , wherein the fluid has progressed through the microchannels. 
         FIG. 12C  depicts another top view of an alternative embodiment of microchannels comprising surface tension guides, wherein gravity assists with the direction of flow. 
         FIG. 12D  depicts a top view of the embodiment of  FIG. 12C , wherein the fluid has progressed through the microchannels. 
         FIG. 12E  depicts a side view of an embodiment of a microchannel comprising at least one rounded ridge. 
         FIG. 12F  depicts a side view of an embodiment of a microchannel comprising at least one square ridge. 
         FIG. 12G  depicts a side view of an embodiment of a microchannel comprising the surface tension guide is provided by a grooved, textured portion. 
         FIG. 12H  depicts a side view of an embodiment of a microchannel comprising a typical open channel for comparison. 
         FIG. 13  depicts a cross-sectional view of a directional-flow branched channel, according to one embodiment. 
         FIG. 14A  depicts a cross-sectional view of an embodiment of the collector having an outflow channel and two reservoirs. 
         FIG. 14B  depicts the channel and reservoir system of  14 A in a horizontal position, such that fluid is directed into the second channel and reservoir by gravity. 
         FIG. 15A  depicts a side view of a reservoir and outflow channel according to an exemplary embodiment. 
         FIG. 15B  depicts the embodiment of  FIG. 15A , wherein the fluid has been transferred to the distal end of the reservoir. 
         FIG. 15C  depicts the embodiment of  FIG. 15B  in a horizontal orientation. 
         FIG. 16A  depicts a perspective, transparent view of a reservoir and an exemplary embodiment of an outflow channel, wherein the channel is configured to be in direct fluidic communication with the bottom inner surface of the reservoir when the collector is in a horizontal position. 
         FIG. 16B  depicts a perspective, transparent view of a reservoir and an exemplary embodiment of an outflow channel, wherein the channel is configured to be in direct fluidic communication with the top inner surface of the reservoir when the collector is in a horizontal position. 
         FIG. 16C  depicts a perspective, transparent view of a reservoir and an exemplary embodiment of an outflow channel, wherein the channel is in a bulb configuration. 
         FIG. 16D  depicts a perspective, transparent view of a reservoir and an exemplary embodiment of an outflow channel, wherein the channel is in a splayed configuration. 
         FIG. 16E  is a perspective, transparent view of a reservoir and an exemplary embodiment of an outflow channel, wherein the channel is in a straight channel configuration. 
         FIG. 17A  is a perspective cross-sectional view of a specific volume reservoir, according to an alternative embodiment. 
         FIG. 17B . is an end-view of the embodiment of  FIG. 17A . 
         FIG. 18A  is a perspective view of a cartridge reservoir, according to an exemplary embodiment. 
         FIG. 18B  is a perspective view of an alternative embodiment of the cartridge. 
         FIG. 18C  is a reverse perspective view of further embodiment of the cartridge. 
     
    
    
     DETAILED DESCRIPTION 
     The various embodiments disclosed or contemplated herein relate to a single device that can be used by untrained or minimally-trained persons to both collect bodily fluid and seamlessly contain the bodily fluid, and related systems and methods. 
     The present disclosure describes the use of microfluidic methods that utilize gravity within open microfluidic channels in a manner which complements the capillary driven flow, and enables new applications that were previously difficult to achieve, including, but not limited to, adding a detachable tube, incorporating one-way flow valves, including geometries more amenable to manufacturing methods, and using engineered connection methods. 
     It is understood that the various embodiments of the devices and related methods and systems disclosed herein can be incorporated into or used with any other known medical devices, systems, and methods. For example, the various embodiments disclosed herein may be incorporated into or used with any of the medical devices and systems disclosed in co-pending U.S. application Ser. No. 13/949,108, filed Jul. 23, 2013, entitled “Methods, Systems, and Devices Relating to Open Microfluidic Channels,” and U.S. application Ser. No. 13/750,526, filed Jan. 25, 2013, entitled “Handheld Device for Drawing, Collecting, and Analyzing Bodily Fluid,” both of which are hereby incorporated herein by reference in their entireties. 
     Disclosed herein are various embodiments of an integrated collection and containment device that collects and transfers the bodily fluid from a subject&#39;s tissue into an easily detachable tube or reservoir. Previous technologies approached the transfer of the bodily fluid in a linear manner: one device enabled the bodily fluid to exit the tissue and another device was used to collect the bodily fluid. In contrast, the implementations disclosed herein simplify the process of bodily fluid collection by integrating the collection of the bodily fluid directly with the containment of bodily fluid within the same device. 
     Certain embodiments utilize gravity as a passive energy source to overcome surface tension in specific and defined areas so as to facilitate the transfer of fluids. As will become apparent, exemplary embodiments described herein include various apparatuses, systems and methods for collecting fluid samples, such as bodily fluids, and enabling the containment of those samples in containers that are easily attached and removed from a collection device. Exemplary embodiments are for use in medical devices, at-home diagnostic devices, and laboratory analysis platforms and equipment. 
     The ability to specifically and intentionally use gravity to overcome or enhance capillary force is useful for the manufacturability of microfluidic channels. When utilizing gravitational force in the direction of the fluid flow, the gravitational force acts as an extra, or additive force to promote the flow of fluid in places that have an unfavorable capillary drawing force for a variety of reasons. For example, materials that have a high surface energy (and thus a large contact angle) often have difficulty drawing fluid. If the channel is oriented such that the input is above the output, fluid will naturally be forced through the channel due to gravity, overcoming the unfavorable surface properties of the plastic and thus enabling a wider range of plastics that can be used in a gravity-assisted capillary device. In certain implementations, this benefit can extend to overcoming various manufacturing defects, allowing these fluid systems to be particularly robust and easy to manufacture, as less precision may be required. Manufacturing defects can include small surface or dimensional imperfections that can create fluidic pinning ridges that would otherwise stop fluid flow, improper manufacturing depth that would reduce spontaneous capillary flow, rounded channel corners, dirt or dust particulates that may land in the channel during assembly, and other imperfections that may exist in the channel and hinder fluid progression in an entirely capillary driven device. 
     The creation or production of small, narrow channels via injection molding reveals a difficulty in the fabrication of previous microfluidic devices. The aspect ratio of height-width is an important parameter for successfully injection molding microchannels. Microfluidic engineers generally prefer tall and thin channels for fluidic functionality, whereas manufacturing engineers generally prefer short and wide channels for ease of manufacturability. When utilizing gravitational force in the direction of fluid flow, a microfluidic engineer can design channels that are shorter and wider to accomplish the fluidic functionality needed for a system, in this case the transfer of bodily fluids. Thus, the utilization of gravity enables complex microfluidic fluid flow in microchannels that are easy to manufacture. 
     The various embodiments described herein also include valves and channels that further extend the functionality of the open microfluidic platforms being utilized. These valves allow for more complex fluid handling within passive microchannels. For instance, the valves can induce timed fluid release or specific volume releases using the disclosed embodiments. Utilizing these same gravity enhancements with channels oriented in the direction of gravity, channels can be designed to create a droplet, and have the droplet connect to another channel after growing to a specific size. This droplet formation can also allow the connection of the channel to any receptacle, including, but not limited to, centrifuge tubes and other attached reservoirs. The step of creating a droplet further allows specific boluses of fluid to be delivered, as the distance to the channel or surface properties of the plastic change the size of the drop necessary to allow gravity to dominate over surface tension and allow fluid flow. Because the fluid is creating a droplet and falling into the next chamber, that chamber can then be easily removed from the channel for further use. The ability to utilize capillary and gravitational forces together to create efficient channels can result in devices that are simpler, less expensive, and easier to manufacture and more robust in their operation because they have higher working tolerances, therefore not requiring as much precision in the channels. This can result in reduced unit cost. As these channels can overcome larger differences in surface energy than capillary-driven devices, the connections can be more easily made with a variety of less-specialized devices, as in the cases of plastic centrifuge tubes or rubber septum reservoirs. The connection with these parts can be easily severed to allow these parts to be removed from the device and sealed with minimal secondary processes, enabling a bodily fluid reservoir to either be connected with no backflow or disconnected from the device entirely or some combination of those steps. 
     Finally, flow in capillary networks can be improved by utilizing gravitational forces. Flow in capillary networks can be limited by two factors: the length of the network and the vertical changes in height between areas of the network. As to network length, increases in length result in corresponding decreases in capillary flow rate, due to the resistance to flow developed by the wetted sections of the channel. The reduction in flow rates is particularly difficult for viscous fluids or non-Newtonian fluids which could render the network unusable. By designing a network in a three-dimensional space that flows with the gravitational field, it is possible to counteract the resistance to flow in order to accelerate or maintain at a constant velocity the flow of the fluid in the network. 
     In the case of capillary networks that have differences in vertical height along the length of the device, the weight of the fluid can cancel the capillary pull force and prevent the flow from occurring. In these instances, there will be a point along the length of the channel at which the fluid front, or leading edge, stops advancing through the channel and which is dependent on the capillary number of the channel, the geometry of the channel, and the composition of the fluid. 
     Turning to the figures with greater detail,  FIGS. 1A-1F and 2A -F depict exemplary embodiments of the gravity-enhanced fluid collection device, or simply “collector”  100 . As is shown in  FIGS. 1A-B , in exemplary embodiments, the collector  100  generally comprises a housing  10  having first  12  and second  14  ends, and which is configured to be in fluidic communication with at least one reservoir  104 , such as a tube or cartridge by way of a fitting or coupling portion  103 , which is also called a “collar” in certain embodiments, and an outflow channel  112 . In exemplary embodiments, the reservoir  104  can be removably attached to the housing  10 , by way of the coupling portion  103 , such that it may be detached, as is shown in  FIG. 1C . In certain embodiments, the reservoir  104  can be a standard Eppendorf tube press-fitted on the fitting  103 . In further embodiments, the reservoir  104  can also be custom made and utilize capillary forces or solely gravitational forces to fill. The tube  104  can thus act as a removable and standardized reservoir  104  for containing or gathering the fluid that can be simply and easily detached and inserted into existing and established testing or lab equipment. By way of example, where the fluid is blood, the tube  104  can be easily inserted into clinical and laboratory equipment or workflows for diagnostics and/or biomarker detections. 
     In use, as best shown in  FIG. 1B , the collector  100  is placed on the skin of a user such that the distal portion  104 B of the fluid reservoir  104  is oriented in a substantially vertically down position. As a result of this orientation, bodily fluids collected at the collection sites  101  are drawn in by the fluidic network  102  for transport out the fluid reservoir  104 . In these embodiments, as best shown in  FIG. 2A , capillary forces allow the fluid to interact and be guided by the individual microfluidic channels  102 A,  102 B,  102 C of the fluidic network  102  which are disposed within the housing to maximize the advantages of the channel geometries, while gravity biases the flow of fluids into and through the fluid network  102 . Additional description of the fluidic and physical connection of the reservoir  104  is set forth below in conjunction to  FIGS. 3A-C ,  5 A- 6  and  15 A- 16 E, for example. 
     As is shown in  FIG. 1D , in exemplary embodiments, the housing  10  further comprises an internal lumen  22 , as has also been previously described in U.S. application Ser. No. 13/750,526, filed Jan. 25, 2013, entitled “Handheld Device for Drawing, Collecting, and Analyzing Bodily Fluid,” which is incorporated herein by reference. Further, certain devices have at least one actuator  110 , and are configured to be placed against the skin of a patient  1 , as is shown in  FIG. 1B . Upon depressing or otherwise operating the actuator  110 , at least one lancet, needle or other skin puncture device (such as the four needles  30  depicted in  FIG. 1D , which is discussed below) is deployed, so as to pierce the subject&#39;s skin and cause blood or other bodily fluid to pool near the collection areas (as shown in  FIG. 4A-D ), for uptake into the microfluidic network. 
       FIG. 1D  is an exploded perspective view of an exemplary embodiment of the collector  100 , in accordance with one implementation. In this embodiment, the actuator  110  functions as a plunger  18  configured to be inserted into the lumen  22  at the proximal end  12  of the housing  10 . This plunger contains a face  28  and a plurality of needles  30  or lancets. The plurality of needles  30  is fixed to the face  28 . A base  20  attaches to the distal end  14  of the housing  10  and contains a plurality of apertures, or collection sites  101  that are in fluid communication with the lumen  22  and match with the number and positions of the needles  30  on the plunger  18  such that the needles  30  extend through the apertures  101 . 
     The plurality of needles  30  may include needles having a gauge from 20 gauge to 40 gauge. In some embodiments, the needles are from 29 gauge to 40 gauge. In an alternative embodiment, the plurality of needles  30  may include a plurality of microneedles. In the embodiment shown in  FIG. 3 , the plurality of collection sites  101  on the base  20  illustratively includes four apertures that match with the needles  30 . In alternative embodiments, the plurality of collection sites  101  may include from two to one hundred apertures. The plurality of needles  30  are aligned to be guided to pass through the plurality of collection sites  32  when a user actuates the actuator  110 , thereby deploying the needles  30 . 
     In certain embodiments, a spring  24  is provided, which retracts the plunger  18  through the lumen  22  from the distal end  14  to the proximal end  12  of the housing  10  after the plunger  18  has been depressed and the force used to depress the plunger  18  has been removed, thereby removing the plurality of needles  30  from the subject&#39;s skin and creating a vacuum in the vacuum creation space  22 , which is the portion of the lumen  22  distal to the plunger  18 . In these embodiments, the vacuum created in the lumen  22  creates a vacuum at each of the collection sites  101 , thereby enhancing the pooling of bodily fluid on the subject&#39;s skin, optimizing fluid extraction from each puncture site where one of the plurality of needles  30  penetrates the subject&#39;s skin, and at the same time minimizing the size of each puncture site. The vacuum created may range from greater than 0 Pa to 75,000 Pa. 
     Within the various collector embodiments, a network of microfluidic channels are utilized to shuttle fluid from the various fluid collection sites to the outflow channel. As will be shown with reference to  FIGS. 1E-F , designing open or closed channels in a collector that utilize a combination of capillary and gravity forces can be accomplished by changing the geometry of the channel or properties of the fluids and device materials. A characteristic number that can be used to design these channels is the Bond number, which is Equation 1:
 
 Bo=ΔμgL   2 /σ  (1)
 
where Δρ is the difference in fluidic density between the fluid flowing in the channel and the fluid surrounding it, g is the gravitational constant, L is the characteristic length of the channel, typically its width, and σ is the surface tension of the fluid.
 
     For Bond numbers lower than 0.1, capillary forces serve as the primary driving forces, and gravity is of lesser influence. At Bond numbers above 10, gravity becomes the primary driving force. For Bond numbers between 0.1 and 10, both capillary and gravitational forces have a definitive effect—that can compete, amplify, or alter one another. For example, if a channel has a negative slope, gravitational forces will amplify the flow and allow the flow to cross defects on the surfaces, grooves, and pinning regions. On the contrary, if the channel has a positive slope gravity will reduce the flow and potentially stabilize the effect of some surface tension features such as pinning valves. Finally, capillary and gravitational forces can be used in conjunction in the design of channels, as described herein, so as to enhance and otherwise direct the flow of a collected fluid. For example, to drive a specific branch of a dividing channel or flow around features that would be in the way of direct gravitational flow by use of capillary features that direct the flow, as is discussed herein. Further, the combination of gravitational and capillary forces can be used to create efficient, cost-effective devices, systems and methods, like those disclosed herein. 
     These features are exemplified in  FIGS. 1E-F , in which a channel  150  contains at least two distinct regions. A first, more narrow region of high capillary force  151  (a low Bond number) and a second, wider region  152  where the Bond number is higher, and gravity plays a more substantial role in the fluid flow. Fluid  154  will be readily drawn into the first region  151  due to the high capillary force. Once the fluid reaches the second region  152 , given the high Bond number, capillary force is insufficient to drive the flow alone, and gravity is then utilized to cause the flow to continue. To function properly, the channel  150  has to have a negative slope relative to the horizontal  153 . Additionally, because less capillary force is being applied, these channels can be designed to retain less fluid. As is described herein, the use of these combinations of forces allows the collector&#39;s microfluidic network to achieve fluid flow in a variety of applications. 
     Example 1: Average Blood Travel Distance 
       FIG. 1G  depicts the average blood travel distance for various channels under experimental conditions. To test the travelled distance of fluid in channels with various geometries, ports, and treatments, a channel of 700 um×1200 um was tested with various channel designs to assess the overall travel distance of the fluid. In this figure, * represents p&lt;0.0001, with an n=10 per condition. Error bars represent standard deviation of the mean. In this example, the channels were designed with an aspect ratio of 700 um wide×1200 um, and the channels treated with 50% dextrose and 1.8 mg/mL EDTA resulted in optimal capillary draw. In  FIG. 1H , the data for various channel geometries is shown. 
       FIGS. 2A-B , depict top-down, cross-sectional views of the internal components of two exemplary embodiments of a collector  100 . In these embodiments, networks of microfluidic channels  102  utilizing both capillary forces and gravity forces can be used to shuttle the blood down small scale channels (typically defined by a capillary number of less than 0.1) and larger channels respectively. In such small channels, the capillary forces are the primary driving forces of fluid movement. 
     In such embodiments, and as best shown in  FIGS. 2A-2B , the collector  100  comprises at least one collection site  101 A,  101 B,  101 C,  101 D disposed within the housing  10 , a fluidic channel network  102 , such as a microfluidic channel network  102 , a coupling portion  103 , an outflow channel  112  and at least one reservoir  104 . Various implementations will feature a variety of numbers and configurations of collection sites, such as the three sites  101 A,  101 B,  101 C shown in  FIG. 2A  or four sites  101 A,  101 B,  101 C,  101 D shown in  FIG. 2B . Other configurations are possible. In various embodiments, as best shown in  FIG. 2A , the reservoir  104  further comprises proximal  104 A and distal  104 B ends. 
     Certain embodiments further comprise at least one ramp  105 , the microfluidic channel geometry which can be defined so as to exploit the maximum vertical height attainable, thereby facilitating the constant flow of fluids through various changes in height. Specific channel geometries can be designed to facilitate fluid flow by the combination of capillary and gravitational forces. 
     A more detailed explanation of the configurations and benefits of such ramps  105  follows. As open microfluidic channels contain open liquid-air interfaces, spontaneous capillary flow can be utilized in certain settings to drive fluid flow. The use of capillary-driven flow to manipulate fluids in complex open microfluidic networks is a novel feature previously unused in open microfluidic channels. In order to insure that spontaneous capillary flow (“SCF”) occur in a channel containing any number of open liquid-air interfaces in its cross-section, an analysis of capillary force was developed, to define a design guideline ensuring that the capillary force provided by the walls of the microfluidic channel overcomes the resistance created by the open sections of the microfluidic channel. 
     The result of the analysis is written in a SCF relation stating that the ratio of the free perimeter (p f ), defined by the length of the cross-section open to air or another medium, and the wetted perimeter (p w ), defined by the length of the cross-section made up of solid hydrophilic material must be less than the cosine of the contact angle (θ) of the fluid with the channel walls. The SCF relation can be written as:
 
 p   f   /p   w &lt;cos(θ*)  (2)
 
     Equation (2) thus defines the set of open channel geometries under which the SCF relation is met. When the SCF relation is satisfied, the channel will drive the flow through the microfluidic network by capillary forces, including against the force of gravity. Importantly, the SCF relation extends to most channel configurations containing open liquid-air and wetted sections. Further, the open liquid-air sections do not have to be continuous or contiguous. Thus the SCF relation still holds for complex channel geometries containing open “windows” on the channel (e.g. a circular aperture in the wall of a channel) as well channels containing multiple open liquid-air interfaces at the same point in the channel (e.g. a fluid completely suspended between two rails in a channel devoid of ceiling and floor). Open microfluidic channels verifying the SCF relation also have the benefit of not being constrained to rectangular cross-sections.  FIGS. 6B-C  depict further views of these applications. 
     With that background in mind, a ramp (such as ramp  105 ) can be used to exploit the maximum vertical height attainable. The vertical height change that a fluid can reach can be evaluated experimentally and analytically using an equation relating to the force of gravitational resistance (F=μgΔh) and the estimation of the force of capillary pull (F=2γ cos(θ*)/R F , where θ* is the equivalent contact angle of the fluid in an open microfluidic channel, and R F  is the fluidic radius of the channel. θ* is defined as cos(θ*)=Σf i  cos(θ i ), where f i  represent the relative length of a section of the channel wall that has a contact angle θ i . R F  represents the fluidic radius of the channel and is defined as R F =2A/P, where A is the cross-sectional area of the channel and P the perimeter of the channel). These two forces allow the estimation of the maximum vertical height attainable by the fluid, as given in Equation 3: 
     
       
         
           
             
               
                 
                   
                     Δ 
                     ⁢ 
                     
                         
                     
                     ⁢ 
                     h 
                   
                   = 
                   
                     
                       γ 
                       ⁢ 
                       
                           
                       
                       ⁢ 
                       
                         cos 
                         ⁡ 
                         
                           ( 
                           
                             θ 
                             * 
                           
                           ) 
                         
                       
                       ⁢ 
                       P 
                     
                     
                       ρ 
                       ⁢ 
                       
                           
                       
                       ⁢ 
                       gA 
                     
                   
                 
               
               
                 
                   ( 
                   3 
                   ) 
                 
               
             
           
         
       
     
     By way of example, in the case of the a rectangular channel of 1 mm width, 1 mm depth and open on the ceiling, with a contact angle of 60 degrees on the plastic surfaces and assumed to be 90 degrees in the open interface areas, filled with water, the maximum vertical height attainable is evaluated to be about 10.5 mm. Further data can be seen in Table 1. 
     
       
         
           
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 Maximum Vertical Height Attainable for Various Channel Geometries 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                   
                 Height (in meters) 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                 0.0001 
                 0.0002 
                 0.0003 
                 0.0004 
                 0.0005 
                 0.0006 
                 0.0007 
               
               
                   
               
               
                 Width 
                 0.0001 
                 107.1429 
                 89.28571 
                 83.33333 
                 80.35714 
                 78.57143 
                 77.38095 
                 76.53061 
               
               
                 (in meters) 
                 0.0002 
                 71.42857 
                 53.57143 
                 47.61905 
                 44.64286 
                 42.85714 
                 41.66667 
                 40.81633 
               
               
                   
                 0.0003 
                 59.52381 
                 41.66667 
                 35.71429 
                 32.7381 
                 30.95238 
                 29.7619 
                 28.91156 
               
               
                   
                 0.0004 
                 53.57143 
                 35.71429 
                 29.7619 
                 26.78571 
                 25 
                 23.80952 
                 22.95918 
               
               
                   
                 0.0005 
                 50 
                 32.14286 
                 26.19048 
                 23.21429 
                 21.42857 
                 20.2381 
                 19.38776 
               
               
                   
                 0.0006 
                 47.61905 
                 29.7619 
                 23.80952 
                 20.83333 
                 19.04762 
                 17.85714 
                 17.0068 
               
               
                   
                 0.0007 
                 45.91837 
                 28.06122 
                 22.10884 
                 19.13265 
                 17.34694 
                 16.15646 
                 15.30612 
               
               
                   
                 0.0008 
                 44.64286 
                 26.78571 
                 20.83333 
                 17.85714 
                 16.07143 
                 14.88095 
                 14.03061 
               
               
                   
                 0.0009 
                 43.65079 
                 25.79365 
                 19.84127 
                 16.86508 
                 15.07937 
                 13.88889 
                 13.03855 
               
               
                   
                 0.001 
                 42.85714 
                 25 
                 19.04762 
                 16.07143 
                 14.28571 
                 13.09524 
                 12.2449 
               
               
                   
                 0.0011 
                 42.20779 
                 24.35065 
                 18.39827 
                 15.42208 
                 13.63636 
                 12.44589 
                 11.59555 
               
               
                   
                 0.0012 
                 41.66667 
                 23.80952 
                 17.85714 
                 14.88095 
                 13.09524 
                 11.90476 
                 11.05442 
               
               
                   
                 0.0013 
                 41.20879 
                 23.35165 
                 17.39927 
                 14.42308 
                 12.63736 
                 11.44689 
                 10.59655 
               
               
                   
                 0.0014 
                 40.81633 
                 22.95918 
                 17.0068 
                 14.03061 
                 12.2449 
                 11.05442 
                 10.20408 
               
               
                   
                 0.0015 
                 40.47619 
                 22.61905 
                 16.66667 
                 13.69048 
                 11.90476 
                 10.71429 
                 9.863946 
               
               
                   
               
            
           
           
               
               
            
               
                   
                 Height (in meters) 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                 0.0008 
                 0.0009 
                 0.001 
                 0.0011 
                 0.0012 
                 0.0013 
                 0.0014 
                 0.0015 
               
               
                   
               
               
                 Width  
                 0.0001 
                 75.89286 
                 75.39683 
                 75 
                 74.67532 
                 74.40476 
                 74.17582 
                 73.97959 
                 73.80952 
               
               
                 (in meters) 
                 0.0002 
                 40.17857 
                 39.68254 
                 39.28571 
                 38.96104 
                 38.69048 
                 38.46154 
                 38.26531 
                 38.09524 
               
               
                   
                 0.0003 
                 28.27381 
                 27.77778 
                 27.38095 
                 27.05628 
                 26.78571 
                 26.55678 
                 26.36054 
                 26.19048 
               
               
                   
                 0.0004 
                 22.32143 
                 21.8254 
                 21.42857 
                 21.1039 
                 20.83333 
                 20.6044 
                 20.40816 
                 20.2381 
               
               
                   
                 0.0005 
                 18.75 
                 18.25397 
                 17.85714 
                 17.53247 
                 17.2619 
                 17.03297 
                 16.83673 
                 16.66667 
               
               
                   
                 0.0006 
                 16.36905 
                 15.87302 
                 15.47619 
                 15.15152 
                 14.88095 
                 14.65201 
                 14.45578 
                 14.28571 
               
               
                   
                 0.0007 
                 14.66837 
                 14.17234 
                 13.77551 
                 13.45083 
                 13.18027 
                 12.95133 
                 12.7551 
                 12.58503 
               
               
                   
                 0.0008 
                 13.39286 
                 12.89683 
                 12.5 
                 12.17532 
                 11.90476 
                 11.67582 
                 11.47959 
                 11.30952 
               
               
                   
                 0.0009 
                 12.40079 
                 11.90476 
                 11.50794 
                 11.18326 
                 10.9127 
                 10.68376 
                 10.48753 
                 10.31746 
               
               
                   
                 0.001 
                 11.60714 
                 11.11111 
                 10.71429 
                 10.38961 
                 10.11905 
                 9.89011 
                 9.693878 
                 9.52381 
               
               
                   
                 0.0011 
                 10.95779 
                 10.46176 
                 10.06494 
                 9.74026 
                 9.469697 
                 9.240759 
                 9.044527 
                 8.874459 
               
               
                   
                 0.0012 
                 10.41667 
                 9.920635 
                 9.52381 
                 9.199134 
                 8.928571 
                 8.699634 
                 8.503401 
                 8.333333 
               
               
                   
                 0.0013 
                 9.958791 
                 9.462759 
                 9.065934 
                 8.741259 
                 8.470696 
                 8.241758 
                 8.045526 
                 7.875458 
               
               
                   
                 0.0014 
                 9.566327 
                 9.070295 
                 8.673469 
                 8.348794 
                 8.078231 
                 7.849294 
                 7.653061 
                 7.482993 
               
               
                   
                 0.0015 
                 9.22619 
                 8.730159 
                 8.333333 
                 8.008658 
                 7.738095 
                 7.509158 
                 7.312925 
                 7.142857 
               
               
                   
               
            
           
         
       
     
     As shown in Table 1, various channel geometries can be contemplated for a given material contact angle (here assumed to be 60 degrees) that contemplate the theoretical maximum vertical height attainable by the fluid, as given in Equation 3. Due to open channel geometry, increases to the width of the channel will affect fluid travel against gravity more than increases to the height. Table 1 depicts the net vertical height (in millimeter) a fluid can travel against gravity. While the distance traveled may vary depending on the orientation of the channel relative to the direction of gravity, the total height achieved will remain the same. The calculated values are the theoretical total height a fluid can travel directly against gravity, thus, as a channel is placed at an angle not directly against gravity, the fluid will be able to travel a greater length along the channel that will not exceed the total theoretical height. In practice, one trained in the art can utilize the theoretical maximum height traveled to engineer fluidic microsystems that contemplate the combination of capillary and gravitational forces. 
     These numbers are well correlated with experimental data collected on such channels. However, regardless of the geometry of the channel, a point of maximum vertical height that a fluid can reach will always exist. The maximum vertical height attainable can increase as the channel is held in various angles that are less than directly opposite to gravity. 
     Utilizing the knowledge of the maximum vertical height for various channel geometries, the disclosed collector embodiments can comprise microfluidic networks with channels designed to facilitate the collection and movement of fluids by a combination of capillary and gravitational forces in a variety of implementations. Additionally, the contact angle can be modified by different treatments of the surface through plasma, chemical, or physical additives. Additives to the channel to improve capillary drive can include EDTA, heparin, dextrose, and other additives that when dried pull fluid up and into the channel. The percentage of dextrose tested showed improved blood pulling capabilities with 50% dextrose dried into the channel. 
     When utilizing gravity to direct fluid flow, more unique channel geometries can be utilized. Therefore filling standardized reservoirs, such as centrifuge tubes or rubber septum reservoirs is easily accomplished. Fluid can also be made to fill larger reservoirs which typically have a low capillary number and thus more sensitive to gravity. Enhancing the flow of blood using gravity also ensures reliability in fluidic connections, at the specific location for example when the fluid must be transferred from the collection device to a detachable reservoir. Typically the small gap that exists at these connection points can act as barriers blocking the advancement of the fluid. With the addition of gravity and well-designed channel geometries these gaps can be cleared reliably. Thus, there is no need to engineer and manufacture specialized outflow channels and/or reservoirs that have a short channel length in order to satisfy the fluid flow requirements imposed by a gravitationally independent microfluidic system. As is shown further in  FIGS. 3A-3C  and  FIG. 6 , these ramps can assist with the movement of fluid from a collection site up and out to the outflow channel. 
     Returning to  FIG. 2A , by utilizing gravitational force as a means of shuttling the fluid, various embodiments can ensure that blood flowing down one of the branches  102 A,  102 B,  102 C of the microfluidic network  102  do not substantially enter the other branches, because, in use, the branches  102 A,  102 B,  102 C are configured to be oriented from the collection sites  101  to the coupling region  103  such that the direction of flow is substantially in line with the direction of gravity (designated with the reference arrow G). By way of example, in certain implementations, the flow can occur between −60 and +60 degrees from the direction of gravity when rotated about the z (normal to the bottom surface) axis. When rotated about the y (along the face of the bottom surface, perpendicular to the direction of gravity in this case) axis, a rotation comprised between +90 and −45 degrees was observed to be functional ( FIG. 1A  also depicts the axis for reference). However, embodiments can be contemplated wherein any direction vector that has a positive component in the direction of gravity will enable flow. 
     In various embodiments, the flow will be proportional to the angle made by the microfluidic channel relative to the direction of the gravitational force. In this manner, the gravity-enhanced microfluidic networks are able to minimize the volume of sample lost passively through backwashing or other non-productive flows in the channels. Further, utilizing gravity-enhanced microchannels, it is possible to empty the channels at the end of the fluid collection and further reduce lost volumes of fluid that may remain within the fluidic network. In these embodiments, once the source of fluid—such as blood flowing from a lancet puncture on the skin—stops providing additional fluid, the channel will simply drain into the tube connected to the channel network. This effect can be maximized by designing a channel that expands as it reaches the reservoir so that capillary action becomes weaker as the fluid reaches the reservoir. Using this approach, gravity will become the primary force, gradually overcoming the capillary forces and thereby minimizing the amount of fluid remaining in the microfluidic channel following outflow. 
     As shown in  FIG. 2B , in alternate embodiments, the microfluidic network can be connected to two or more tubes or reservoirs  104 ,  108 . In this specific example, the reservoirs  104 ,  108  are positioned on alternate sides of the collector  100 . Utilizing this approach, the device  100  can allow the collection of fluid in one of the reservoirs  104 ,  108  even in the event that the user places the device  100  in the wrong direction. The device  100  is similarly placed on the skin of the user in any vertical direction. The bodily fluid pooling at the surface of the skin in the collection sites  101  is captured by the fluidic channel network and, depending on the orientation of the device  100 , gravity will bias its flow down the most descending channel. In one embodiment, there are two channels  102  and  106 , or alternatively there can be any number of channels if more degrees of freedom on the placement of the device  100  are desired. As the fluid flows through the channel ( 102  or  106 ), it will be raised from the plane of the channel network into the reservoirs by fluidic ramps  105  or  107 , as is described further below in relation to  FIGS. 3A-C  and  5 A- 6 . Reservoirs  104  and  108  are connected on each end and the reservoir ( 104  or  108 ) located lower vertically will become the reservoir receiving the fluid. In other embodiments, any number of reservoirs can be designed. In yet other embodiments, these reservoirs can be standardized Eppendorf tubes press fitted onto the device  100  by a fitting  103 . Importantly, as the fluid does not enter or minimally enters channels that go in an ascending direction, the addition of these channels does not incur a loss of fluid. Further, in certain embodiments in which the capillary number is low, the fluid will be drained from the channels into the reservoirs at the end of the fluid collection or fluid flow, minimizing the loss of fluid in the reservoirs.  FIGS. 2C-F  depict various exterior side views of the embodiments of  FIGS. 2A &amp; 2B , including the various shapes of the actuator  110  and the orientation of one or more tubes or reservoirs  104 ,  108 . 
     As shown in  FIG. 3A-C , in certain embodiments, the collector  200  is configured such that fluid is collected in a detachable tube or reservoir (as shown in  FIG. 1C , for example) or standardized tube using a U-shaped, suspended, or outflow channel  205  that extends into the center of the tube (such as tube  104  of  FIGS. 1A-C ) as part of a tube connection  206  and can be elevated from the initial collection site by a channel  207  which serves as a ramp  207  (as best shown in  FIGS. 3B-C ). By using open microfluidic system ramps  207  for fluids, the various embodiments of the collector  200  can be configured so as to raise or lower the channel plane to any level (as can be seen, for example, in reference to  422  in  FIG. 6 ), such that the relative height of the fluid flow can be changed without reducing or stopping the fluid flow. These movements of fluid in a vertical direction (up or down) can also contribute to the enhancement of the fluid flow. Accordingly, the fluid can be directed through the outflow channel  205  and into a reservoir or tube (such as tube  104  of  FIGS. 1A-1C ). 
     In operation, the collector  200  is placed on the skin of the user (such as shown in  FIG. 1B  with respect to another collector embodiment). As described, blood being collected at one or multiple collection sites  201 A,  201 B,  201 C are captured in a fluidic channel network  202 , which comprises a plurality of branched channels  202 A,  202 B,  202 C which are disposed so as to utilize both capillary and gravitational forces when the outflow channel is oriented in the direction of gravity G. When the fluidic channel network is placed in a descending manner, gravity will enhance the flow of fluids down the channels  202 A,  202 B,  202 C. As discussed above, in certain embodiments, a ramp  207  can be used to connect the fluids flowing in the network to the outflow channel  205 , which allows the filling of a reservoir (not shown). As with the embodiment shown in  FIG. 1C , the reservoir (not shown) used with the connector  200  can be a detachable reservoir that can be removably connected to the device  200 . In the example of a standard test tube, the fitting can be a simple press fitting region  204  to which a standard tube is reversibly coupled to create a fluidic seal. In exemplary embodiments, these fittings may be twist or snap fittings, as would be apparent to one of skill in the art. The fitting  206  is sealed to the reservoir, such that the connecting fluidic channel or outflow channel  205  spans into the reservoir (as shown in  FIG. 6 ), thereby allowing the fluid flowing into it to touch a wall or other feature of the reservoir. This serves as a fluidic bridge (which is also called a “capillary bridge”) which allows the fluid to transfer into the reservoir, as is described for example in relation to  FIGS. 9A-D  and  15 A- 16 E. 
     The collector  200  is thus able to collect fluid from a site on the subject&#39;s skin and shuttle it to the outflow channel  205  using a combination of capillary and gravitational forces. As a second aspect, once the fluid reaches the distal outflow channel  205 , it is preferable to have it flow into the reservoir (not shown) as efficiently as possible. As is shown variously in the figures, in certain embodiments the outflow channel can extend the length of the tube/reservoir such that the flowing fluid is able to contact the internal distal end of the tube or reservoir (as is shown in  FIGS. 9A-D  at  905  and discussed below). In further embodiments, the outflow channel extends partially into the tube, thereby allowing the collected fluid to contact a side of the tube and descend to the distal end (as is described further below in relation to  FIGS. 15A-16E ). Accordingly, the outflow channel can be placed at any height relative to a longitudinal plane of the tube or reservoir, thereby allowing the contact of the fluid at any location in the tube, as is desired by the user based on the specific application. Further, gravity can be used to enhance the ability of fluids flowing down the outflow channel to interact and contact the reservoir or tube). In certain embodiments, an extended microfluidic outflow channel allows for a preferable connection with a wall or floor of the reservoir or tube by creating a simple fluidic bridge which allows reliable flow of fluid into the reservoir. In these embodiments, gravity can be used to simply induce a positive curvature of the fluid in the outflow channel such that the fluid bridges to the reservoir and can contact a feature even in the presence of an air gap between the outflow channel and the wall of the reservoir. Gravity can thus also be utilized to create a drop of fluid that will only contact the walls of the reservoir of the tube when a sufficient volume drop has been reached. Further embodiments are described in relation to  FIGS. 9A-D  and  16 A-E. 
     As is shown, for example, in  FIG. 3D , in certain embodiments a fluidic bridge  209  is established between the outflow channel  205  and the reservoir  208 , thereby forming a fluidic bridge  209  and enabling a continuous flow of the fluid  210  into the reservoir along the inner wall  208 A of the reservoir  208 . Further, this embodiment can be utilized as a conditional valve for preventing the reverse flow out of the reservoir once the fluid has been collected and the device is placed in a different orientation, as is shown in  FIGS. 9A-9D . When placed in an orientation where the reservoir or tube is located at the lowest point, the fluid flows into the reservoir and fills it. After the flow has stopped and the device is placed on a horizontal surface, such as a laboratory benchtop or a desk, the fluid may move to fill the tube sideways. Provided less than a determined volume of fluid was collected in the tube, the level of the fluid will not reach the channel in this orientation and thus prevent any backflow into the device. Further embodiments are described in  FIGS. 15A-C ,  16 A-E. 
       FIGS. 4A-D  depict further embodiments of the collector  300 , wherein the microfluidic channel networks  302  are configured to utilize both capillarity and gravity to perform essential fluidic functions. In these embodiments, the collector  300  is configured to collect fluids from the various collection areas  301 A,  301 B,  301 C,  301 D and to shuttle the fluid through one or more microfluidic channels  302 A,  302 B,  302 C,  302 E,  302 F,  302 G,  302 H to a connection  303 A,  303 B to a reservoir or analytical device (not shown). In these embodiments, at least one of the channels  302 A,  302 B is placed in a descending orientation (as described previously in relation to  FIG. 2A ), and multiple channels  302  can be used to increase the probability and/or ensure that at least one of the channels  302  is in such a descending orientation. 
     As is shown in  FIG. 4A , fluids collected in a large open area  304  or fluids flowing down from another collection area  301  and reaching a large opening  304  can be guided using a capillary ridge  305  in the direction of a channel  302 . Capillary forces (in the form of Concus-Finn effects for example) on a wedge and angle of the ridge or ridges  305 A,  305 B will promote the liquid in the form of drops or a continuous flow to remain close to the ridge, or ridges  305 A,  305 B, as would be apparent to one of skill in the art. In these embodiments, gravity will promote motion of the droplets or slow continuous flow of fluid downwards until it reaches the opening of a channel  302 A,  302 B. In such embodiments, the ridge is configured to facilitate continuous fluid flow due to the capillary forces created. In various similar embodiments, there is a geometric shape or a sufficiently low surface energy introduced such that the shape drives the capillary action whereby the capillary forces are a principle driving force underlying fluid flow. 
     In the embodiment of  FIG. 4B , various inner channels  302 C,  302 D,  302 E,  302 G can connect fluid from one or more fluid collection sites  301 A,  301 B,  301 C,  301 D such that fluid from a first collection site  301 A will flow downstream through a channel  302 G to reach a second collection site  301 B. Further, the fluid can be directed around the collection site utilizing capillary forces and gravity by designing a wedge  307 A that links a first collection site  301 B with the channel  302 B opposite a second collection site  302 H. These wedges  307 A,  307 B,  307 C,  307 D surround the fluid collection sites  301 A,  301 B,  301 C,  301 D and allows the fluid to link into the channel by wedge fluid flow. In exemplary embodiments, the wedges are recessed plastic wedges around the collection sites  301 A,  301 B,  301 C,  301 D, which are therefore sent into the luminal side of the base  20  on the distal end  14  of the housing  10 , as shown in  FIG. 1D  and would be apparent to one of skill in the art. Accordingly, provided that the fluidic path is consistently and substantially in line with gravity, fluid inputted from each “higher” collection site can be transferred around the lower collection site in a controlled, robust, and clean way. This method prevents needless flow of a previously collected bodily fluid over an exposed skin area for example. 
     In another exemplary embodiment shown in  FIG. 4C , fluid collected from each collection site  301 A,  301 B,  301 C,  301 D can be transferred through channels such as open microfluidic channels  310 A,  310 B,  310 C,  310 D in which capillary force dominates into channels  302 A,  302 B,  302 C that are biased by gravity. In this example, as the fluid in each open microfluidic channel  310  reaches gravity channel  302 , it will flow in the descending direction, or direction of lower potential energy, as described in relation to  FIGS. 1E-F , for example. This system allows the minimization of the overall number of channels required as all collection sites feed into a common channel that can be used bi-directionally. 
     In yet a further embodiment, and as shown in  FIG. 4D , the capillary channels  315 A,  315 B,  315 C,  315 D transferring bodily fluids from the collection sites  301 A,  301 B,  301 C,  301 D can be placed in any direction because they are dominated by capillary forces, and once they reach a main channel  302 A,  302 B, gravity will bias their flow in the descending direction toward the lower outflow channel  303 A,  303 B. This allows for flexibility over where the fluid is delivered between the collection sites  301 A,  301 B,  301 C,  301 D and the main fluidic network  302 A,  302 B. Importantly, Concuss-Finn effects in the wedges of the main channel can be utilized to promote the extraction of fluids from the capillaries  315 A,  315 B,  315 C,  315 D. At the point of contact between the capillary channels  315 A,  315 B,  315 C,  315 D and the main channels  302 A,  302 B the use of a rounded junction and/or sufficiently low surface energy of the material will allow fluid to robustly flow out of the capillary channels  315 A,  315 B,  315 C,  315 D, into the main channels  302 A,  302 B, where the flow of the fluid will be enhanced by gravity. 
     The various embodiments depicted in  FIGS. 5A-6  demonstrate a further integrated blood collection and containment device, or collector  400 . In various embodiments, the collector  400  features at least one closed-open or one open-closed-open microfluidic system configured to promote the flow of fluid from the internal microfluidic channel network (described in relation to  FIGS. 1A-4 ) into a detachable reservoir  402 . One aspect is a detachable reservoir  402  which is capable of being separated from the integrated collection device  400  for seamless integration into existing laboratory processing methods and processes, as it may be easily fitted to coupling region  408  and/or the skirt  410  of the device  400  and later removed, as is shown in  FIG. 5C  at reference arrow A. In these embodiments, the tube or reservoir  402  is coupled to the device  400  at the collar or plastic skirt  410  which creates a fluidic and/or air-tight seal with the inner surface  401  of the reservoir  402 . The inner surface  401  is correspondingly in fluidic and physical communication with an outflow channel  414  contained within an outflow channel housing  412  (as described at surface  420  in relation to  FIG. 6 ) such that fluid collected by the device flows through the microfluidic channel network(s) as a fluidic bridge into the reservoir  402  for collection by way of capillary and gravitational forces. Further embodiments of the fluidic bridge and outflow channel are discussed in relation to  FIGS. 3D and 15A-16E . 
     In particular embodiments, the collector  400  functions by being placed on the skin of the user or subject (similarly to the steps of the embodiment described above and depicted in  FIGS. 1A-C ) with the reservoir  402  directed downwards (relative to gravity) and depressing the actuator  404 . In various embodiments, the device  400  and reservoir  402  may comprise a hermetic or fluidic seal  401 , and the actuation of the button  404  may cause the pressure in the device  400  and reservoir  402  to decrease, thus enhancing the blood flow out of the skin of the user. Gravity and capillary force then guide blood into the reservoir  402 , as was previously described. In certain phases, the driving force behind the fluid draw can be caused by microfluidics and/or pressure differential. By way of example, in certain implementations the pressure differential can be the primary force in drawing fluid out of the skin into the channels, while the microfluidic forces account for the movement of blood through the channel or network. 
     Specifically, being able to transfer the collected bodily fluid sample from an integrated microfluidic collector  400  into a reservoir  402  or other collection reservoir that is easily detachable from the device is novel in the field of capillary blood collection. The bodily fluid collected from the patient is transferred through an outflow channel  414  into the reservoir  402 . At the end of use or when the desired volume of blood is collected in the reservoir  402 , it can simply be detached by pulling it off by several known methods, such as a press-fitting or twisting it off of a threaded structure  408 A which is defined on the fitting  408 . 
     The fluidic connection allowing robust transfer of the bodily fluid between the device  400  and the reservoir  402  is created through the outflow channel  414 . The outflow channel  414  is capable of being inserted into the tube, which is correspondingly sealed around the plastic skirt  410 . Accordingly, in exemplary embodiments, the microfluidic outflow channel  414  is comprised of the first open microfluidic channel  424  in fluidic communication with the internal microfluidic channel network described in relation to  FIGS. 1A-4C . In these embodiments, the first open microfluidic channel  424  functions as a ramp, as described for example in relation to reference numbers  105  and  107  in  FIG. 2 . 
     This outflow channel  414  is detailed further in reference to  FIG. 6 . In certain embodiments, the outflow channel  414  is further comprised of several microfluidic channels  424 ,  418 ,  422 , and configured such that one of these microfluidic channels has a portion  422  facing the reservoir  402 . Returning to  FIGS. 5A-6 , from this first “open” area  424 , the fluid is then able to flow to the “closed” microfluidic channel  418 , and then again to a second “open” microfluidic channel  422 , such that it is urged or otherwise brought into contact with the inner surface  420  of the tube  402  and collected in the reservoir  402  by way of a fluidic bridge. In these embodiments, the open microfluidic system therefore allows capillary flow of the blood to the exposed portion, allowing contact of the blood or bodily fluid with the reservoir  402 . 
     Accordingly, and as shown in  FIGS. 5D-6 , the shape the outflow channel  414  can vary along its length to first enhance capillary flow to include a closed microfluidic channel  418  and progressively increase the cross-sectional length connected to the inner surface of the tube  420  (as is shown at the ramp at  422 ) in order to force the fluid to connect with the inner tube surface, bridge and flow into the reservoir  402 . Accordingly, open microfluidics associated with gravity allow the flow of blood along an outflow channel  414  without causing it to “pin” or otherwise stop or pool when the fluidic path suddenly opens into the reservoir  402 . These open microfluidic methods allow the gradual transition towards creating a drop of blood or a blood connection with the tube, thereby preventing blocking, pinning, or clogging. As best shown in  FIG. 5E , the air opening  416  between the volume of air contained in the reservoir  402  and the volume of air in the device  400  with the shape of a cylinder or any other shape allows the equilibration of air pressures between the reservoir  402  and the inside of the device  400  while the fluid is filling the reservoir  402 . 
     In various embodiments, certain open microfluidic channels, such as those depicted in  FIGS. 6B-C . In embodiments wherein the ramps are working against gravity, they may be composed of free surfaces and wetted surfaces satisfying the SCF relation (as laid out by Eq. 3, stating that the ratio of the length of the cross-section of channel spanning over the at-least one free surface the length of the cross-section of channel spanning over the at-least one wetted is less than the cosine of the contact angle of the fluid on the wetted surface), which thereby allows spontaneous capillary flow. In various alternative embodiments wherein the ramps work with the assistance of gravity, the SCF relation need not be satisfied. 
     Importantly, the ability to connect an integrated blood collection device with a detachable reservoir  402  or cartridge (shown in  FIG. 19  at  1900 ) has many advantages. One advantage is the ability to simply couple or otherwise interface the reservoir with downstream equipment and measuring devices. The ability to simply press or screw a tube or other collection device onto the integrated blood collection device allows the use of any desired tube for downstream applications, including tubes for various assays and applications, such as PCR, which in certain embodiments may contain PCR reagents, as shown at  426  in  FIG. 6 , as well as various microcentrifuge tubes, tubes containing gel for plasma separation, standard tubes used in blood analysis laboratories for pediatric applications, tubes that perform a specific assay directly within the tube, tubes that stabilize or otherwise store the blood for shipping, and capillary blood collection tubes. The tubes connected to the integrated bodily fluid collection device can also be specific to blood collection, including tubes that contain EDTA, heparin, serum separation gel, biomarker stabilization reagents, or any other pre-processing blood collection tube. A tube can also be replaced by a customized reservoir that is used for dedicated downstream equipment or processes. While the examples provided herein refer to a tube, as would be apparent to one of skill in the art, various embodiments of fluid containers are well within the scope of the embodiments described herein. 
     Another advantage of the detachable reservoir being in fluidic communication with the outflow channel is that the fluidic transfer from the tissue to the reservoir is engineered to simplify the multi-step process of blood collection into a single step process. Therefore, the user of the device does not need to be trained in the art of tissue puncture, device handling during the fluid transfer process, or post-collection processes including tissue sealing, handling of an exposed biospecimen, or other processes. The integrated collection device described includes open microfluidic fluid transfer but the device can perform the fluid transfer using any number of transfer mechanisms including metal tubing, plastic tubing, and/or sealed microchannels. The tube or reservoir is sealed from the exterior environment post-collection and can remain so during detachment of the tube and after the tube is detached. The tube or collection reservoir filled with the bodily fluid can be detached by twisting, pulling, activating a release mechanism, or any other secondary step. This tube can then also have a known features, device, or component that provides for self-sealing the tube during and following detachment. Alternatively, the removal mechanism can activate other steps that may be helpful in stabilization, sample preparation, or diagnostic analysis. 
     Gravity-enhanced microfluidics can be utilized to precisely control the nature of the fluidic connection between the device and the tube. In the embodiment described in  FIGS. 5A-6 , only a single section of the open microfluidic path  422  is removed to allow connection with the tube  420 , thereby ensuring that sufficient capillary force allows the fluid to be flowed past the change in geometry, as is also described in the commonly assigned U.S. patent application Ser. No. 13/949,108, filed on Jul. 23, 2013, which is incorporated by reference in its entirety. A central aspect to such embodiments is the ability to reliably transfer fluids between a collection device and a reservoir utilizing open microfluidic systems. 
     The use of such open microfluidic methods allow for outflow channels  414  that can be transiently in contact with a reservoir, container, or reservoir  402  while allowing reliable and simple fluid transfer between the various aspects. In certain embodiments, the outflow channel  414  favors capillary flow at the innermost aspect by presenting a closed channel geometry thus allowing a robust draining of the fluid into the outflow channel from the microfluidic network. Progressively, the geometry of the fluidic path along the outflow channel varies to an open channel configuration in which part of the fluid is allowed to come in contact with the air or a different surface, as is shown at  422 . In order to ensure a strong probability of contact, that interface must be large enough to allow the fluid to contact the new surface and create a drop of sufficient volume that it flows by itself on the surface  420 . This flow can be enhanced by surface treatment of the reservoir through a surface activation or the addition of a dried reagent that reduces the surface energy of the material and allows increased wetting by the fluid or implementing a material in the manufacture of the features that has a preferential surface energy, such as a hydrophilic plastic. Importantly as there is no binding material between the outflow channel and the receptacle or tube it can be removed or placed back in contact when needed. 
     As is shown in  FIGS. 6B-6C , these open microfluidic channels  450  typically involve at least one free surface  452  and at least one wetted surface  454  defining boundaries of a cross section  456  known as the “free perimeter” (at  462 ) and “wetted perimeter,” (at  454 ) respectively. In certain exemplary embodiments, the cross-section  456  of the microfluidic channel  450  verifies the SCF relation stating that the ratio of the length of the cross-section spanning over the at-least one free surface  452  to the length of the cross-section spanning over the at-least one wetted surface  454  is less than the cosine of the contact angle  458  of the fluid  460  on the wetted surface  454 , ensuring that fluid spontaneously flows by capillary force along the open channel  450 . 
       FIGS. 7A-7D  provide expanded views of microfluidic channels  800  such as those incorporated into the various collector embodiments discussed above. As shown in  FIGS. 7A-B , in various embodiments of the gravity-enhanced microfluidic system  800 , the flow of fluid  801  through a channel  802  can be regulated by way of a surface tension valve  805  placed between the first  800 A and second  800 B channel portions or lengths and configured such that the fluid  801  reaches a gap  807  in the channel which comprises the surface tension valve  805  and is only able to span over the gap  807  by creating a drop-like feature  803  able to flow along the channel  800 . In exemplary embodiments, this is only possible when the channel  800  is placed substantially vertically (as by rotation around reference arrow A) such that the fluid is flowing with the gravitational field (shown by reference arrow G). In these embodiments, an opening  807  is created in the channel path  800  between the first  800 A and second  800 B channel lengths such that the fluidic network is disconnected for most traditional fluid flows, as shown in  FIG. 7A , where the surface tension valve  805  is preventing the flow of fluid  801  through the opening  807 . 
     As is shown in  FIG. 7B , when the channel  800  is oriented in a substantially vertical position, the additional force of gravity allows the fluid  801  to overcome these surface tension forces in the gap  807 , thereby forcing the fluid to connect with the second portion  800 B of the fluidic channel. In these embodiments, once the fluid  801  contacts the second channel portion, a sustainable fluid path is created allowing flow. Further, when the channel  800  is returned to a substantially horizontal position, fluid is then unable to flow back into the first portion  800 A fluidic network. 
     As is shown in  FIGS. 7C-D , in another embodiment, fluid  801  flowing down a first channel portion  800  reaches a gap  807  in the channel  802  and is only able to span over the gap  807  by creating a drop-like feature  803  that contacts the second channel portion  800 B, which in this embodiment further features an expansion  810 . Once the fluid  801  has connected to the second channel portion  800 B, it is able to fill a reservoir  811 , which is situated opposite the expansion  810 . At any time or at the end of the flow, a lid  812  can be placed in the gap  807 , allowing the sealing of the second half of the microfluidic channel  810  as well as the reservoir  811 . 
     As is shown in  FIG. 8 , in an alternative embodiment, a first channel portion  800 A can be designed to control delivery of fluid  801  into a second channel portion  800 B. Fluid  801 , flowing in a channel  800 , again reaches a gap  807  in the fluidic network and expands into a drop-like feature  803  if and only if the fluid is flowing in the direction of the gravitational field, as has been discussed. Once the drop-like feature  803  connects to the second channel portion  800 B, a pre-determined volume of the fluid will be released from the drop-like feature  803 . In these embodiments, the connection occurs when a droplet (the volume of which is easily determined though standard equations) reaches a height that is equal to the length of the gap  807 . At that volume, fluidic connection occurs, the droplet is drained to the other side, and the interface recedes to a low volume position. The fluid  801  is thereby applied to the second channel portion  800 B periodically and with controlled and tailored volumes. The addition of additional channel features  804 , such as capillary fins, surface tension guides, protrusions or thin-walled ridges disposed within the second channel  800 B can assist in the wicking of the expanding drop-like feature  803  into the second half  800 B of the microfluidic network. Once the drop-like feature  803  is released, the fluid in channel  802  will recede back to the position of the gap and in reference to the Bond number discussed, e.g., in relation to  FIGS. 1E-F . In various implementations, this process can repeat as long as there is available fluid  801  to be delivered to the system. 
     In the embodiment depicted in  FIGS. 9A-D , various microfluidic networks  900  can be utilized which connect with a reservoir, or tube  904  (as discussed variously herein, such as in relation to  FIGS. 1A-C ) such that fluid  906  can flow into the tube  904  when upright (as is shown in  FIGS. 9A &amp; 9C ), but not flow back out of the tube  904  when placed horizontally (as is shown in  FIGS. 9B &amp; 9D ). This can be accomplished by designing a channel with an appropriate Bond number relative to the angles at which it will be disposed, as is discussed above in relation to  FIGS. 1E-F . In these embodiments, gravity is significant, and the fluidic paths will be influenced by gravity such that they may take different paths as the device is placed in different orientations. 
     In these embodiments, when the collection device  901  is substantially upright (as depicted in  FIGS. 9A and 9C ), the fluid  906  is able to flow through the internal microfluidic network  902  (as described in relation to  FIGS. 2A-4D ) and is raised from that channel surface through a ramp  903  into the tube  904  by capillary action and gravity. An outflow channel  905  is in fluidic contact with the inner surface of the tube  904  (which may occur either at the top or bottom of the tube, as is also described in relation to  FIGS. 16A-B ). The outflow channel  905  thereby delivers the fluid  906  into the tube  904  either by proximal fluidic connection with the bottom of the tube so as to create a fluidic bridge and fill the tube ( FIG. 9A ) or by creating a fluidic bridge  907  with the side of the tube (shown in  FIG. 9C ) that drips down the side and into the tube  904 , thereby filling it. 
     When moved to the horizontal position (as depicted in  FIGS. 9B and 9D ), if the fluid  906  falls to the bottom of the tube  904  or if the fluid is capillary pinned in the tube  904  via changes in surface tension, such as by changing the tube design, engineered microfluidics, material selection and/or low fluid volume, the fluid  906  cannot flow back out of the tube  904  into the device  901 . In this way, bodily fluid can be collected and prepared for removal or shipping without the possibility of leakage. 
     In an embodiment depicted in  FIG. 10 , exemplary embodiments further comprise a reservoir  1000  which is a detection well  1004 . In these embodiments, the well  1004  is configured such that electronic probes having detection pads  1003  can be integrated into the well  1004  by one or more electrical leads  1002  so that fluids can be applied to the well  1004  by one or more outflow channels  1001 . One of the obstacles to placing leads into wells is that leads cannot be run across or over right angles, and instead require less abrupt changes in direction for fabrication simplicity. In these embodiments, an open well  1004  is provided such that at least one outflow channel  1001  can deliver fluids into the open well  1004  and electrical leads  1002  can be integrated into the well for analysis and detection by way of the pad  1003  or pads in a manner which does not require the leads to be placed over a sharp corner. 
     The smooth transition  1006  enables electrical contact of the lead  1002  with the detection pad  1003  during its transition into the well  1004 . Utilizing gravity ensures the filling of the open well  1004  as fluid is flowing down from outflow channel  1001  despite the well  1004  not having a defined contour on its entire periphery  1005 . The ability to define smooth transitional surfaces  1006  into the well  1004  facilitates low-cost electronic patterning technologies, including ink-jet printing. Further, in the depicted embodiment, the outflow channel comprises an outflow channel  1001  which is a deep channel  1001  which is further in fluidic communication with a connecting channel  1007 , thereby allowing the controllable flow of fluids through the connecting channel  1007  across the smooth transition  1006  by the formation of a fluidic bridge, as has been previously discussed. In various embodiments, these electric leads  1002  can be easily imprinted, ink jet printed, or patterned into the well  1004  by a shallow and smooth transition  1006 . 
     The use of gravity in combination with capillary forces allows the collector to overcome manufacturing defects. By way of example,  FIG. 11  depicts a channel  1101  that can be incorporated into any of the collector embodiments discussed elsewhere herein, such as in the microfluidic network within the lumen, the outflow channels, or ramps. This exemplary channel helps to explain some of the benefits of gravity-assisted microfluidic devices with respect to manufacturing due to the reduction in the need for precision. When the channel  1101  is held in a position that allows the fluid flow to be assisted by gravity, fluid  1102  can flow past pinning ridges  1103 , which can result from unintentional manufacturing defects, dust particles, or other capillary interferences. This ability to pass such ridges  1103  to make the fluid flow, and therefore the collector devices more reliable. Accordingly, in various embodiments, the precision of the channel dimensions and/or configurations can be reduced while maintaining reliable fluid flow. 
     As is shown in  FIGS. 12A-D , by using gravitational assistance, certain exemplary embodiments of the collector can comprise microchannels which contain surface tension guides which can run substantially the length of the channel  1200  and influence the direction of fluid flow within it. More specifically, in various embodiments, these microfluidic channels  1201  can be designed with surface tension guides  1202  in the form of fluidic pinning ridges or hydrophilic patterns  1202  which allow a fluid  1203  to be guided in a specific direction. In this way, when the devices are oriented such that gravity assists the direction of the flow (as is shown in  FIGS. 12A-D ), fluid can be more specifically manipulated and moved for more complex fluid motion. These manipulations can involve bends in the channel  1204 , engineered fluid flow such as velocity or other features that are known to those of skill in the art. 
     As shown in  FIGS. 12E-H , the surface tension guides, ridges, or patterns, are simple features that add texture or grooves in the surface, preferably with sharp edges that will incur Concus-Finn capillary flow in the direction of the texture. As can be seen in  FIG. 12E , in one embodiment, at least one rounded ridge  1210  can be provided within the channel. As shown in  FIG. 12  F, at least one square ridge  1212  is given. In  FIG. 12G , the surface tension guide is provided by a grooved, textured portion  1214 , and in  FIG. 12H , a typical open channel  1216  is shown for comparison. 
       FIG. 13  depicts an alternative embodiment comprising a bifurcated channel  1302  having a primary channel  1302 , first  1302 B and second  1302 C branches and, wherein the channel  1302  is configured to prohibit backflow into an unused branch (such as branch  1302 C or branch  1302 B). In this embodiment, the primary channel  1302  is oriented so as to have a component of the gravitational force  1301  influence the fluid flow such that fluid  1304  from  1306  will be urged to flow to a confluence or junction  1305  and flow preferentially in the direction of gravity  1301  and into the primary channel  1302  without flowing up into the empty channel  1302 B via capillary force. As would be apparent to one of skill in the art, the use of a combination of gravitational forces to overcome any capillary forces can be dictated by the specific application. 
     In the embodiment of  FIG. 14A-B , the collector can be used to deliver fluid in a timed manner. In these embodiments, fluid  1404  is collected from a site  1401  and directed along a first channel  1402  into a reservoir  1403 . In these embodiments, collected fluid  1404  can then exit the reservoir  1403  when placed horizontally ( FIG. 14B ) to flow back through the collection channel  1402 , through a second channel  1405  and into a second reservoir  1406 , because of the introduction of gravitational forces. In certain embodiments, this second reservoir  1406  can also utilize gravitational assistance to allow fluid to flow exclusively into the second channel  1405  instead of the first channel  1402 . In this way, tests that need specific timing of fluid addition for chemical reactions or other more specific biological reactions can have the fluid enter the testing chamber (second reservoir  1406 ) as a single bolus of fluid. 
     Microfluidic channels such as those discussed in relation to the outflow channels tend to retain fluid. This creates two specific design issues. First is the desire to collect as much fluid from the channel as possible in the reservoir. Second is the need to prevent fluid backflow into the outflow channel when the orientation of the reservoir is changed and fluid which has gathered in the reservoir can come back into contact with fluid retained in the outflow channel, thus causing backflow. Various outflow channel embodiments are disclosed herein which address aspects of these issues. In certain implementations, the outflow channel is in direct fluidic communication with the side of the tube, such as is shown in  FIG. 3D . However, when inverted or positioned such that the tube is on its side (or horizontal), these embodiments may allow a simple fluid path for the fluid to drain back into the collector. To avoid this reverse fluid flow, various alternative outflow channel geometries were created that will allow device inversion without contact between the fluid and the outflow channel, such as those discussed at  FIGS. 9A-D  and in relation to  FIGS. 15A-16E . 
       FIGS. 15A-D  depict various embodiments of an outflow channel  1500  that allow device inversion without the fluid in the tube coming into contact with the outflow channel and the fluid retained there, as shown in  FIG. 15B . In these embodiments, the outflow channel  1500  extends from the collector such that the distal end of the channel  1500  is disposed within the tube or reservoir  1502 , thereby providing the initial transitional point for the flow of fluid  1504  (as is described herein, for example, in relation to  FIGS. 5A-6C ). The outflow channels in  FIGS. 15A-D  and  16 A-E are similar in that they contemplate outflow channel geometries that act as one-way flow valves. In this sense, the fluid is able to flow by dripping into the tube, but when the device and tube are inverted, the channel  1500  will not allow backflow out of the tube. 
     This specific action is shown in  FIGS. 15A-C . In  FIG. 15A , the fluid  1504  flows out of the outflow channel  1500  into the tube  1502 . When the flow of fluid  1504  is complete as shown in  FIG. 15B , the fluid  1504  is within the tube  1502 . When the device is held at a different orientation, as shown in  FIG. 15C , the fluid  1504  is retained in the tube  1502  and not allowed to make contact with the outflow channel  1500 , which could allow fluid  1504  to flow back into the device via backflow through the outflow channel  1500 . In the embodiments of  FIG. 15C , this retention is achieved because the shape of the tube tip  1502 A and properties of the fluid  1504  are such that surface tension in the fluid is sufficient to hold the fluid in the tip despite the orientation. In contrast, in certain embodiments such as the embodiment of  FIG. 15D , surface tension may be insufficient to prevent gravity from drawing the fluid  1504  out of the tip  1502 B and down onto the side of the tube  1502 C, for example when large amounts of fluid have been collected. In those embodiments, the channel  1500  is positioned in the tube  1502  such that the fluid  1504  disposed along the side of the tube  1502 C does not contact the channel  1500 , thereby preventing backflow out of the tube. 
     Further embodiments of this outflow channel  1500  are contemplated in  FIGS. 16A-E  for the same action and purpose as shown here in  FIGS. 15A-D . In  FIG. 16A , one embodiment features an outflow channel  1600 A having first  1604 A and second  1606 A channel edges which are in fluidic connection  1605 A with the inner surface  1607  of the tube  1602 A. That is, the two channel edges  1604 A,  1606 A are in contact with the inner surface  1607  such that fluid  1605  that flows out of the outflow channel  1600 A will come in contact with the inner surface  1607  of the tube  1602 A. Thus, when the device and tube  1602 A are substantially upright, the fluid is able to flow out from the outflow channel  1600 A and into the tube  1602 A, and when it is rotated in the direction of reference arrow A fluid  1605  is brought into contact with the inner surface  1607 A of the tube. 
     As is shown in  FIG. 16B , an alternative embodiment features an outflow channel  1600 B featuring first  1604 B and second  1606 B channel edges which are in fluidic connection  1605 A with the top surface  1608  of the tube  1602 B such that when the device and tube are substantially upright, the fluid is able to flow out from the outflow channel  1600 B, thereby being brought into contact with the inner surface of the tube  1608 . When the tube is laid down flat (in the direction of reference arrow B), the front face of the tube thus becomes the top face, and gravity pulls the fluid  1605  down and away from the outflow channel, thereby preventing fluid flow back into the collector. 
     As is shown in  FIG. 16C , a bulb-type outflow channel  1600 C comprising first  1604 C and second  1606 C channel edges which form a bulbous shape may be utilized so as to not connect or physically contact to any edge or surface of the tube  1602 C. Instead, this outflow channel  1600 A allows fluid  1605  to drip from the outflow channel  1600 C into the tube  1602 C, without a fluidic bridge being formed to the inside of the reservoir  1602 C to influence fluid flow. In certain embodiments, notches  1609  at the distal end of these outflow channels can help facilitate droplet formation and droplet detachment, by weakening surface tension forces in the outflow channel. 
     As is shown in  FIG. 16D , a splayed outflow channel  1600 D is utilized, wherein the first  1604 D and second  1606 D channel edges extend away from one another at the distal ends. This splayed configuration accommodates fluid drop into the tube  1602 D by increasing the space between the first  1604 D and second  1606 D channel edges, thereby increasing the relative role of gravity on the fluid when dripping. 
     Finally, in  FIG. 16E , a narrow “straight channel” outflow channel  1600 E can be employed, so as to further move the outflow point at the distal end of the channel  1612  away from the top edge  1620  and inner surface of the tube  1602 E. In certain applications, the embodiment of  16 E is preferred, because these embodiments introduce substantial distance  1610  between the collector and the distal end of the first  1604 E and second  1606 E channel edges, which prevents dripping fluid from contacting the inner surface of the tube  1602 E. This distance  1610 , along with the narrow shape of the channel  1600 E also reduces the chance of backflow caused by fluidic connection between the fluid  1605  from the outflow channel  1600 E and the inner surfaces of the tube  1602 E, as increases in distances between surfaces inhibit fluidic bridging. That is, the distance  1610  between the proximal  1614  and the distal ends  1612  of the channel edges  1604 E,  1606 E reduces the chance of a fluidic connection by releasing the fluid  1605  at a distance apart from both the top edge of the tube  1620  and the top edge of the collecting fluid  1605 B, thereby preventing pooling and the creation of fluidic bridges regardless of the orientation of the channel. 
     In  FIGS. 17A-B , certain alternative embodiments of a specific-volume collection device reservoir  1700  are shown, wherein the reservoir  1700  comprises at least two reservoir channels  1703 ,  1705 . In this embodiment, the reservoir  1700  has an opening  1701 , that can be coupled to a fluid collector, including any collector embodiment disclosed or contemplated herein. The opening  1701  may be of the same diameter as a standard tube discussed above in relation to  FIGS. 1A-C . In these embodiments, the reservoir  1700  connects to a blood collection device in such a way that a fixed receiving feature  1702  extends into a first reservoir channel  1703  of defined volume. The receiving feature  1702  is thus fixedly disposed along the wall of the reservoir, such that at the proximal end  1702 A it is able to be in fluidic communication with an outflow channel of the collector  1710 , and at the distal end  1702 B is able to fill the reservoir  1703 . The blood being collected is therefore able to contact the outflow channel  1710  more readily than if it required to contact the surface of the tube. Thus the blood will be guided by the receiving feature  1702  to the base  1703 A of the first reservoir channel  1703 , thereby allowing the first reservoir channel  1703  to be filled first in sequence. Once filled, angled features  1704  on the top of the reservoir  1703  guide excess fluid into a secondary reservoir  1705 . The secondary reservoir channel  1705  can thus be utilized as an overfill reservoir, sequestering the excess blood or as a subsequent reservoir for blood containment. In alternative embodiments, multiple reservoirs, such as three, four, five or more reservoirs can be filled sequentially in this fashion. 
       FIG. 17B  depicts a top view of the embodiment detailed in  FIG. 17A . 
     Importantly, the second channel  1705  can further comprise a cross-sectional shape that insures efficient filling, as would be understood by one of skill in the art. For example, an angled corner  1706  can be placed on the reservoir  1700  such that it has a higher capillary affinity. In these embodiments, fluid inputted into the secondary reservoir  1705  through the angled features  1704  will contact the narrow portion  1708  of the secondary reservoir  1705  and guide the blood to the bottom floor  1705 A of the reservoir, thereby allowing a robust filling without creating air bubbles. 
     In these embodiments, fluid originating from the collector is drawn into a tube (such as tube  1700 ) connected to the device that has multiple cavities or reservoir channels (such as channels  1703 ,  1705  discussed above) of known and precise volume, so as to enable blood collection and analysis in applications that require a specific volume of fluid. The transfer of blood from the device to the tube (such as tube  1700 ) is facilitated by features along the length of the tube on the inner diameter. These features can be small channels, grooves, or texture that enable capillary guidance of the fluid into the various reservoirs. For example, a single raised outflow channel (such as the outflow channel  1702  discussed above) spanning from the top of the tube to the reservoir can be used to decrease the gap distance between the tube and the fluid output in the blood collection device as well as guide the fluid along the side of the tube into the desired reservoir. This protrusion can be of various heights, such as from 50 um up to several millimeters. Similarly, multiple outflow channels disposed side by side can be used to form an open channel oriented down the side of the tube and into the reservoir of interest. These features protrude outwards to fit into an open microfluidic channel in the device, thereby enhancing the contact of blood from the device to the tube. The blood flows down the tube assisted by the force of gravity. The features guide the flow along the side of the tube into the appropriate reservoir, allowing the initial filling of that reservoir to a specific volume. As discussed above with respect to the tube  1700 , once the first reservoir is full, the subsequent reservoirs are allowed to fill, thereby guaranteeing a set volume in the specific reservoir or reservoirs. These features can be used to collect a determined amount of fluid and discard the excess in overfill reservoirs or collect multiple aliquots of blood in separate reservoirs. 
       FIG. 18A  depicts an embodiment of a circular cartridge reservoir  1900  that can be used with any of the collector embodiments discussed above. In these embodiments, the cartridge  1900  contains a containment region  1901  designed using open microfluidic principles, thereby allowing the reservoir  1900  to be devoid of a ceiling, top, or any type of cover. In exemplary embodiments, the region  1901  has a T-shaped open microfluidic outflow channel  1903  and a protrusion  1902  fluidically connected thereto. The T-shaped channel  1903  has no “ceiling” and is in fluidic communication with the microfluidic network of the collector when coupled thereto.  FIGS. 18B-C  depict the cartridge protrusion  1902  ( FIG. 18B ) which establishes the fluidic connection with the collector (not shown) ( FIG. 18C ). As best shown in  FIG. 18C , this configuration of the channel  1903  and protrusion  1902  allows for fluid communication with a corresponding collector protrusion  1906 , which in this embodiment is oriented with an inverse T-shape relative to the protrusion  1902  and channel  1903  on the cartridge  1900  such that the collector protrusion  1906  is mateable with the protrusion  1902  and channel  1903 . The collector protrusion  1906  therefore contains corresponding open microfluidic channels  1904 ,  1905  as well. Further, in exemplary embodiments, the cartridge protrusion  1902  and collector protrusion  1906  can be freely rotated relative to one another, such that they can be brought into and out of fluidic communication. 
     These geometries allow the free motion of one protrusion relative to the other as the T shape channel allows for such motion. As the collector protrusion  1906  contacts the cartridge protrusion  1902 , blood is able to bridge between the two channels and flow from one to the other, thereby filling the containment region  1901 . Fluidic connections can be ceased by simply rotating the cartridge, thereby allowing its removal from the blood collection device. 
     Although the disclosure has been described with reference to preferred embodiments, persons skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the disclosed apparatus, systems and methods.