US20100282766A1 - Low-Dead Volume Microfluidic Component and Method - Google Patents

Abstract

A method is described for reducing a dead volume of a microfluidic circuit that includes, in one embodiment, a reservoir, an outlet, and a microfluidic flowpath fluidly connecting the reservoir and the outlet. The method includes providing a variable-volume fluid chamber between the reservoir and the outlet for performing a function and in fluidic communication with the microfluidic flowpath, wherein the variable-volume fluid chamber includes a total volume including a working volume and a dead volume. The working volume is a volume necessary for the variable-volume fluid chamber to perform the function and the dead volume is a volume unnecessary for the variable-volume fluid chamber to perform the function. The method includes configuring the variable-volume fluid chamber to reduce the dead volume, such that the working volume of the component is substantially the same as the total volume.

Description

FIELD OF THE INVENTION
• This invention relates generally to a system and method of reducing dead volume in a microfluidic circuit and, more specifically, to a system and method of reducing the dead volume in a component utilized within microfluidic circuits.
BACKGROUND
• Microfluidic circuits are utilized in various personal medical devices (e.g., insulin infusion devices) to control delivery of medications or other fluids. In general, the volumetric flow rates within these circuits are very low, due to low dosing schedules, and to allow for accurate control of the medication being delivered. The low flow rates, however, can prevent the circuit from being quickly filled prior to utilizing the device, which can pose a significant inconvenience to the user. Additionally, any excess volume within the circuit results in medication that remains undelivered once a pressure source for the medication is terminated.
• Lengthy fill times and undelivered medication are related to total volume within a microfluidic system. Each component (e.g., reservoirs or other chambers, valves, conduits or channels, pressure sensors, flow restrictors, etc.) of a system has an internal capacity for a volume of fluid. This capacity is defined, in part, by the internal dimensions, function, and configuration of the component, including moving components within the flowpath. Manufacturing methods and tolerances may affect the capacity, as well. While a particular component may only require a relatively small portion of the total internal volume to perform its function (this volume may be referred to as the “working volume”), access required for manufacturing the component may prevent minimizing the total volume. This excess volume (or “dead volume”) over that of the working volume increases the total volume of the flow component and, subsequently, of the fluidic circuit of the delivery system.
SUMMARY OF THE INVENTION
• In one aspect, the invention relates to a method for reducing a dead volume of a microfluidic circuit having a reservoir, an outlet, and a microfluidic flowpath fluidly connecting the reservoir and the outlet, the method including providing a variable-volume fluid chamber located between the reservoir and the outlet for performing a function and in fluidic communication with the microfluidic flowpath. The variable-volume fluid chamber includes a total volume having a working volume and a dead volume, wherein the working volume is a volume necessary for the variable-volume fluid chamber to perform the function and the dead volume is a volume unnecessary for the variable-volume fluid chamber to perform the function. The method includes configuring the variable-volume fluid chamber to reduce the dead volume, such that the working volume is substantially the same as the total volume. In an embodiment, the configuring step results in the total volume being substantially the same as the working volume.
• In yet another embodiment, the variable-volume fluid chamber includes a base surface, an inlet, and a separate outlet. The configuring step includes providing a flexible membrane, wherein the base surface and the membrane define a first volume when the membrane is proximate the base surface, and the base surface and the membrane define a second volume when the membrane is displaced by a fluid pressure away from the base surface. The membrane can be biased towards the base surface. In another aspect, the invention relates to a low-dead volume variable-volume fluid chamber manufactured in accordance with the method of the above embodiment. In an embodiment of the above aspect, the working volume is about 5% of the total volume.
BRIEF DESCRIPTION OF THE FIGURES
• Other features and advantages of the present invention, as well as the invention itself, can be more fully understood from the following description of the various embodiments, when read together with the accompanying drawings, in which:
• FIG. 1 is a schematic diagram and related time/volume tables of an exemplary infusion device microfluidic circuit;
• FIG. 2 is a schematic diagram of another exemplary infusion device microfluidic circuit in accordance with one embodiment of the invention;
• FIG. 3 is a schematic diagram of a theoretical microfluidic circuit flow component; and
• FIGS. 4A and 4B are schematic sectional views of an exemplary variable-volume chamber and a low-dead volume version of the same variable-volume chamber in accordance with one embodiment of the invention.
DETAILED DESCRIPTION
• Consider one embodiment of amicrofluidic circuit10 for delivering a fluid medication to a patient, as depicted inFIG. 1. The fluid delivery or flow components of thiscircuit10 include, in series, an elastomer reservoir orbladder12, afirst channel14, aflow component16, asecond channel18, and anoutlet20. Theflow component16 may function, e.g., as a storage chamber for doses of medicament to be delivered on an infrequent basis to a human user orpatient24. Thereservoir12 is filled with medication via a one-way inlet valve22. In this example, themicrofluidic circuit10 is utilized in an insulin infusion delivery device used to deliver insulin to thepatient24 via a subcutaneous cannula in fluidic communication with theoutlet20. The lower table included inFIG. 1 depicts information relevant to a low-dead volume version of themicrofluidic circuit10. The upper table depicts information relevant to a baseline version of themicrofluidic circuit10 upon which no volume reduction modifications have been made. The total volume of each flow component is depicted inFIG. 1 in Row A of both the upper and lower tables. Theelastomer reservoir12 supplies the downstream microfluidic circuit flow components with insulin until the elastomer no longer exerts sufficient pressure to overcome the flow resistance in thecircuit10. At that point, in this example, 87.39 μl of insulin remains in thereservoir12. See Row D.
• Row B in both the upper and lower tables depicts the flow rate Q through the various components. The flow rate Q is defined, at least in part, by flow restrictors and other components present within the circuit. Row C in both the upper and lower tables depicts the amount of time required for insulin to completely fill each dry flow component once flow from thereservoir12 is initiated, as the sum of which is the total start-up time for the entiremicrofluidic circuit10 to fill. This total start-up time reflects the time required to deliver a first dose of insulin to theuser24. Notably, the difference in volume between a standard flow component16 (21.22 μl) and a low-dead volume flow component16 (8.34 μl) contributes directly to the significant reduction in total start-up time of thecircuit10. Note that the fill time for thestandard flow component16 is over twice that of the low-dead volume fill time, while the total fill time of the standard circuit is over 1 hour and 15 minutes greater than the microfluidic circuit using a low-dead volume component. This significant delay inherent in the baseline version of thecircuit10 is both an inconvenience and could be a risk to the user's health.
• Row D in both the upper and lower tables depicts the amount of insulin that is effectively trapped within themicrofluidic circuit10 once theelastomer reservoir12 can no longer induce flow at theoutlet20. Note that a significant portion of the trapped insulin, other than that remaining in thereservoir12, is contained within theflow component16. Accordingly, use of a low-dead volume flow component, for example, a variable-volume chamber, is advantageous to reduce the total amount of lost insulin within themicrofluidic circuit10.
• FIG. 2 is a schematic diagram of an exemplary infusion devicemicrofluidic circuit100 that benefits from the low-dead volume technology described herein. Other infusion device microfluidic circuits benefit as well, such as those described, for example, in U.S. Patent Application Publication No. 2005/0165384 A1, published Jul. 28, 2005, the disclosure of which is hereby incorporated by reference herein in its entirety. Microfluidic circuits having other configurations or utilizing any number of other components also may benefit from inclusion of the low-dead volume variable-volume fluid chamber described herein. Themicrofluidic circuit100 includes areservoir102 that is, in this case, comprised of an elastomer bladder. Afill port104 is used to introduce insulin to themicrofluidic circuit100. In thismicrofluidic circuit100, introducing insulin via thefill port104 fills both thereservoir102 and a variable-volume bolus reservoir106. Checkvalves108 in thecircuit100 prevent backflow of insulin in a number of locations.
• During use, insulin is forced from thereservoir102 due to contraction of the elastomer bladder, through afilter110, and into two parallel flowpaths: abasal flowpath112 and abolus flowpath114. Thebasal flowpath112 delivers a constant dose of insulin to a user; thebolus flowpath114 delivers a bolus dose of insulin to the user as needed or desired by the user, upon actuation of abolus button118. Thebasal flowpath112 includes apressure sensor116 or other flow sensor in communication with theflowpath112. To deliver a bolus via thebolus flowpath114, the user presses thebolus button118 that drives a single stroke (delivering a single dose) of abolus displacement chamber120 and opens twovalves122. Thevalves122 are in series providing failsafe redundancy for safety purposes.Flow restrictors124 limit the rate of fluid flow through theflowpaths112,114. Theparallel flowpaths112,114 join at acommon channel126, upstream of an internal chamber or acannula void128. Thecannula void128 is formed in acannula base130, that provides a fluidic connection to acannula132. Thecannula132 extends below theskin134 of the user, thus delivering the insulin subcutaneously. In the depictedmicrofluidic circuit100, reducing the dead volume in the variable-volume bolus reservoir106 decreases the dead volume throughout the entiremicrofluidic circuit100.
• FIG. 3 depicts atheoretical flow component200. While most flow components utilized in a microfluidic circuit serve specific purposes, each generally share several common elements, as depicted inFIG. 3. First, the flow component includes a housing or some other inner physical boundary that is in contact with the fluid passing therethrough. InFIG. 3, this innerphysical boundary202 is depicted as a hollow cube. Second, the flow component includes an inlet, through which fluid flows into the component. InFIG. 3, theinlet204 penetrates a wall of thephysical boundary202 defined by corners bearing the letter “A”; the dimensions of theinlet204 are defined by a height h, and a width w, although theinlet204 could be circular or any other shape. Third, the flow component includes an outlet, through which fluid flows out of the component. InFIG. 3, theoutlet206 penetrates a wall of thephysical boundary202 defined by the corners bearing the letter “B”; the dimensions of theoutlet206 are defined by a height h, and a width w, in this case, matching the dimensions of theinlet204, although theoutlet206 could be any shape or size and disposed at any location along theboundary202.
• The inner physical boundary of a flow component defines three volumes: a total volume V, a working volume W, and a dead volume D. The total volume V is the volume bounded by the inner physical boundary; accordingly, inFIG. 3, the total volume V is defined by the walls of the cube (i.e., the inner physical boundary202). The working volume W is the minimum volume required to perform the function of the flow component, including connecting fluidicly the inlet and the outlet. InFIG. 3, assume that thetheoretical flow component200 functions as a constant-volume chamber through which fluid passes (where the entire cube must be filled with fluid via theinlet204 prior to any fluid exiting the cube via the outlet206). The working volume W is the volume defined around astraight line208 from a center C_iof theinlet204 to a center C_oof theoutlet206, the straight line having a length L. The actual volume of this working volume W may be defined, in part, by the total length of straight line L and the height h and width w of theinlet204 and theoutlet206, assuming the working volume has outer dimensions substantially similar to height h and width w. Therefore the working volume W may be defined approximately by equation (i) below.
• 
  W=h×w×L  (i)
• The dead volume D is the volume of theflow component200 unnecessary to perform the function, and may be defined as the difference between the total volume V and the working volume W (in this case, the remainder of the volume contained within the innerphysical boundary202, not including the working volume W), as shown in equation (ii) below.
• 
  D=V−W  (ii)
• By reducing the dead volume D of a flow component, the dead volume of a microfluidic circuit may be decreased, approaching, ideally, a condition where the total volume of the low-dead volume component V_LDequals the working volume W of a standard-dead volume flow component, i.e., V_LD=W.
• Different implementations may be utilized to decrease the dead volume of a flow component. In general, however, the dead volume-reduction example described herein may effectively configure the flow component to reduce the dead volume, such that the working volume is substantially the same as the total volume or as close to the total volume as reasonably achievable, under the circumstances. Regardless of the configuration change implemented, a number of factors may be considered. For example, the function and operational performance of the flow component should not be affected adversely by the dead volume-reduction configuration change. The dead volume-reduction change should consider the potential impact on pressure losses associated with the flow component. Care should be taken when reducing dead volume of a flow component, to ensure the component can still be manufactured at acceptable cost. An example of the use of dead volume-reduction configuration change to reduce the dead volume of a flow component is described below.
EXAMPLE
• FIG. 4A is a schematic sectional view of a variable-volume chamber500. Thechamber500 is formed within asolid housing502 and has arigid base surface504, as well as aninlet506, and anoutlet508. A rigidtop surface516 defines the upper surface of thechamber500. As can be seen inFIG. 4A, the entire volume of aninternal chamber500abelow aline510amust be filled before any fluid may pass out of theoutlet508.
• Depicted inFIG. 4B is a variable-volume chamber500′ according to one embodiment of the present invention with reduced dead volume. In this case,membrane510′ is biased or disposed against therigid base504 of theinternal chamber500a′ to define a first small volume approaching zero, as depicted here. As fluid enters theinternal chamber500a′, themembrane510a′ expands512′. The pressure contained withinexpansion volume514′ is immediately exerted against themembrane510a′ and the fluid contained within theinternal chamber500a′. Pressure within theexpansion volume514′ may be relieved by a suitable vent, not shown. Due to the initial location of themembrane510a′, once filling begins, pressure is essentially immediately exerted against the fluid, without requiring filling of an excessive dead volume of theinternal chamber500a′.
• In one embodiment, the variable-volume chamber500 depicted inFIG. 4A includes a total volume V of 230 μl. Of this amount, 218.5 μl was determined to be dead volume D and was subsequently reduced bymembrane510a′, leaving a working volume W of 11.5 μl. For this embodiment, then, reducing the dead volume D results in a working volume W that is about 5% of the total volume V for the variable-volume chamber500′ ofFIG. 6B, thus achieving a 95% reduction in the volume of the variable-volume chamber500. Other reductions are also contemplated.
• Application of the low-dead volume technique described herein can significantly reduce dead volume of amicrocircuit100 such as that depicted inFIG. 2. As depicted inFIG. 2, thebasal circuit112 includes apressure sensor116 and acannula void128. Thebolus circuit114 includes a variable-volume chamber106 and twovalves122. The total volume of all conduits in themicrocircuit100 is about 7 μl, of which nearly none is dead volume. TABLE 1, below, depicts relevant properties of a low-dead volume variable-volume chamber, in an exemplary microcircuit, as that component is described in the Example. Other flow components in an exemplary microcircuit, as depicted in TABLE 1, may include at least acannula void128,valves122, and apressure sensor116. Assuming amicrocircuit100, such as that depicted inFIG. 2, the difference in volume of a standard microcircuit (having a baseline-volume fluid chamber) versus the volume of a low-dead volume circuit (having a low-dead volume variable-volume chamber) is depicted.

• TABLE 1
  Reduction in Dead Volume for Microcircuit Utilizing Low-Dead
  Volume Variable-Volume Chamber

  				Improvement
  Component	V (μl)	D (μl)	W (μl)	(% Reduction In V)

  Bolus Reservoir	230	218.5	11.5	95
  106
  Other Flow	25.26	0	25.26	0
  Components
  AllConduits	7	0	7	0
  Total	262.26	218.5	43.76	83.3

• TABLE 2, below, depicts other relevant properties of a low-dead volume variable-volume chamber, in an exemplary microcircuit, as that component is described in the Example. The total volume V and dead volume D of a standard flow component is provided. Other flow components in an exemplary microcircuit, as depicted in TABLE 2, may include at least acannula void128,valves122, and apressure sensor116. In TABLE 2, thecannula void128 flow component is set aside separately, because its flow rate is different than the other flow components. After utilizing the low-dead volume structure described herein, dead volume D of the variable-volume chamber was essentially eliminated, to achieve the significantly smaller, essentially idealized, working volume W. Also provided is the cumulative volume for all conduits within the microcircuit.
• Flow rates Q through each component are also provided. The flow rates Q are used to calculate the fill time for each component. Initially, the fill time for the exemplary fluid chamber is calculated before any dead-volume reduction structure is utilized. In that case, total volume V is divided by the flow rate Q to obtain the fill time for that component. Next, the fill time for the variable-volume chamber is calculated after the dead-volume reduction structure is utilized. In that case, working volume W is divided by the flow rate Q to obtain the fill time for the low-dead volume variable-volume chamber. It should be noted that the working volume is, as defined above, the minimum volume required to perform the function of the flow component. Since the function of the chamber is to hold liquid medicine, it has been assumed here for the purposes of illustration of the concept that a minimum of 11.5 μl is required for the functional working volume. Indeed, the working volume and dead volume of the variable-volume chamber may change as the chamber is made to hold different amounts of liquid medicine.
• Reduction in fill times from that of the standard baseline component to that of the low-dead volume component are also provided. As noted above, while the reduction in fill time for the Example is quite large, this reduction varies depending on the working volume W selected and results in a significant reduction in fill time for the complete circuit.

• TABLE 2
  Reduction in Fill Time for Microcircuit Utilizing Low-Dead Volume Variable-
  Volume Chamber

  				Flow	Fill	Fill	Fill Time	Improvement
  			W	Rate	Time V	Time W	Reduc.	(%
  Component	V (μl)	D (μl)	(μl)	Q (μl/hr)	at Q (hr)	at Q (hr)	(hr)	Reduc.)

  Cannula Void	1.74	0	1.74	5	0.348	0.348	0	0
  128
  Bolus	230	218.5	11.5	10	23	1.15	21.85	95
  Reservoir 106
  Other Flow	23.52	0	23.52	10	2.352	2.352	0	0
  Components
  AllConduits	7	0	7	185	0.038	0.038	0	0
  Total	262.26	218.5	43.76	N/A	25.738	3.888	21.85	84.9

• The various materials utilized in the flow components described herein, as well as the microfluidic circuits in which those flow components are utilized, may be metal, glass, and/or any type of polymer suitable for sterilization and useful for delivering insulin or other medicaments subcutaneously. Polyurethane, polypropylene, PVC, PVDC, EVA, and others are contemplated for use. More specifically, medical-grade plastics may be utilized for the cannula itself, as well as other components that contact or otherwise penetrate the body of the patient. Needles made from medical-grade stainless steel are also desirable, to prevent failure associated with use. Accordingly, the components utilized to reduce the dead volume within the various components should be the same as, similar to, or at least compatible with the existing materials utilized.
• While there have been described herein what are to be considered exemplary and preferred embodiments of the present invention, other modifications of the invention will become apparent to those skilled in the art from the teachings herein. The particular methods of manufacture and geometries disclosed herein are exemplary in nature and are not to be considered limiting. It is therefore desired to be secured in the appended claims all such modifications as fall within the spirit and scope of the invention. Accordingly, what is desired to be secured by Letters Patent is the invention as defined and differentiated in the following claims, and all equivalents.

Claims (5)

1. A method for reducing a dead volume of a microfluidic circuit comprising a reservoir, an outlet, and a microfluidic flowpath fluidly connecting the reservoir and the outlet, the method comprising:

providing a variable-volume fluid chamber located between the reservoir and the outlet for performing a function and in fluidic communication with the microfluidic flowpath,

wherein the variable-volume fluid chamber comprises a total volume comprising a working volume and a dead volume, wherein the working volume comprises a volume necessary for the variable-volume fluid chamber to perform the function and the dead volume comprises a volume unnecessary for the variable-volume fluid chamber to perform the function; and

configuring the variable-volume fluid chamber to reduce the dead volume, such that the working volume is substantially the same as the total volume.

2. The method ofclaim 1, wherein the configuring step results in the total volume being substantially the same as the working volume.

3. The method ofclaim 1, wherein the variable-volume fluid chamber comprises a base surface, an inlet, and a separate outlet, and wherein the configuring step comprises:

providing a flexible membrane wherein the base surface and the membrane define a first volume when the membrane is proximate the base surface, wherein the base surface and the membrane define a second volume when the membrane is displaced by a fluid pressure away from the base surface, and wherein the membrane is biased towards the base surface.

4. A low-dead volume variable-volume fluid chamber manufactured in accordance with the method ofclaim 3.

5. The low-dead volume variable-volume fluid chamber ofclaim 4, wherein the working volume comprises about 5% of the total volume.

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