Patent Application
20060023039
The present invention relates generally to microfluidic cartridges, and more particularly to microfluidic cartridges that include one or more reservoirs for storing one or more substances such as reagents for a period of time.
There has been a growing interest in the manufacture and use of microfluidic systems for the acquisition of chemical and biological information. Microfluidic systems include devices with features having dimensions on the order of nanometers to 100s of microns, which cooperate to perform various desired functions. For example, micro fluidic devices can be adapted to perform material analysis and manipulation functions, such as chemical, biological and/or physical analyses. Many microfluidic systems have the advantages of increased response time, smaller required sample volumes, and lower reagent consumption. When hazardous materials are used or generated, performing reactions in microfluidic volumes may also enhance safety and reduces disposal quantities.
In some cases, microfluidic cartridges are used in conjunction with a cartridge reader. The cartridge reader may, for example, provide support functions to the microfluidic cartridge. In some cases, for example, the cartridge reader may provide electrical control signals, light beams and/or light detectors, pneumatic control flows, electric flow drive fields, signal processing, and/or other support functions.
In some microfluidic cartridges, on board reservoirs are provided for storing reagents or the like that are used to perform the desired material analysis and/or manipulation functions, such as chemical, biological and/or physical analyses. In many cases, these reservoirs are not adapted to store reagents or the like for an extended period of time. As such, the reagents or the like must be loaded into the reservoirs just prior to use of the cartridge to ensure accurate results. In many applications, however, it would be desirable to load the reagents or the like into at least some of the reservoirs well before the microfluidic cartridge is actually used. This may, for example, allow more precise control over the quality and quantity of the reagents in the reservoirs, as well as an increase in the ease of use of the microfluidic cartridge in the field.
The present invention is directed toward a microfluidic cartridge that includes at least one reservoir for storing a reagent or the like for an extended period of time. In one illustrative embodiment, at least part of a wall of the reservoir includes a hydrophobic material, such as a polymonochlorotrifluoroethylene (PCTFE) homopolymer and/or copolymer, as desired. The hydrophobic material may help reduce leaching, evaporation, diffusion and/or other transfer of the reagent or one of its components from the reservoir. When the reagent or the like is lyophilized, the hydrophobic material may help keep water, water vapor and/or other gases or liquids from entering the reservoir prior to use of the microfluidic cartridge.
Other objects of the present invention and many of the attendant advantages of the present invention will be readily appreciated as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawings, in which like reference numerals designate like parts throughout the figures thereof and wherein:
The illustrative microfluidic cartridge 10 includes three reservoirs 12a, 12b, and 12c. At least one of the reservoirs 12a, 12b and 12c is adapted to accept and store a substance or material, such as a sample, a reagent, or the like, depending on the application. The sample may be, for example, a blood sample. The reagent may be, for example, a lysing agent, a sheath fluid or any other suitable reagent or substance in liquid, gas or solid form, as desired.
In some illustrative embodiments, one or more of the reservoirs 12a, 12b and 12c may store a fluid, such as a buffer fluid, a reagent fluid, a lyse fluid, a sphering fluid, a diluent, a sheathing fluid, a fluorescent dye, a cytochemical stain, a detergent, a monoclonal antibody, a monoclonal antibody with an attached fluorescent dye, a phosphate buffered saline, an electrolyte solution, an enzymatic cleanser and/or a sample fluid to be analyzed.
In some cases, the sphering fluid may be, for example, a sphering reagent that is adapted to sphere red blood cells. The detergent fluid may be, for example, a detergent III and/or a detergent IIIA, which may be a balanced electrolyte solution for use as a rinsing and hemoglobin blanking diluent. The diluent may be, for example, a balanced electrolyte solution for use as a diluent for blood cell counting and/or sizing. The lyse fluid may be, for example, a fluid that can help make a simultaneous quantitative determination of hemoglobin and white blood cells. The lyse fluid may also be, for example, a hemoglobin/lyse for the quantitative determination of hemoglobin. The enzymatic cleanser may be, for example, a concentrated enzymatic cleanser manufactured for automated and semi-automated hematology instruments. The electrolyte solution may be, for example, a balanced electrolyte solution for use as a diluent for blood cell counting and/or sizing. These are just some example fluids 10 that are suitable for use with the present invention.
In the illustrative embodiment, each reservoir 12a, 12b and 12c includes a channel 14a, 14b and 14c, respectively. The channels 14a, 14b and 14c may be used to deliver the sample, reagent, and/or any other suitable substance from the corresponding reservoirs 12a, 12b and 12c to a fluidic circuit (not explicitly shown) on the microfluidic cartridge 10. The fluidic circuit may be used to perform, for example, desired material analysis and/or manipulation functions, such as chemical, biological and/or physical analyses, including in some cases, cytometry. In some cases, and as shown in the illustrative embodiment of
In accordance with the illustrative embodiment, one or more of the reservoirs 12a, 12b and 12c may be adapted to store a reagent or other substance for an extended period of time. This may help increase the shelf life of the microfluidic cartridge. In one illustrative embodiment, at least part of a wall of at least one of the reservoirs 12a, 12b and 12c includes a hydrophobic material, such as a polymonochlorotrifluoroethylene (PCTFE) homopolymer and/or copolymer. The hydrophobic material may help reduce leaching, evaporation, diffusion and/or other transfer of the reagent or other substance, one of its components, from the reservoir. When the reagent or other substance is lyophilized, the hydrophobic material may help keep water, water vapor and/or other gases or liquids from entering the reservoir prior to use of the microfluidic cartridge. The lyophilized substance may be hydrated prior to use by, for example, providing a hydrating fluid into the reservoir via a channel or the like. The hydrating fluid may be stored in another reservoir, if desired. In some cases, the lyophilized substance and hydrating fluid may be mixed once the hydrating fluid is transported to the reservoir that includes the lyophilized substance. In some cases, the lyophilized substance and hydrating fluid may be mixed in-situ using a micro-pump, a vibrator, a moving paddle, or any other suitable mixer, as desired.
In the illustrative embodiment, the first layer 22 has inner surfaces 28a, 28b, and 28c facing the reservoirs 12a″, 12b″ and 12c″, respectively. In some embodiments, at least one of the inner surfaces 28a, 28b, and 28c includes a hydrophobic material, such as a Polymonochlorotrifluoroethylene (PCTFE) homopolymer and/or copolymer. In some embodiments, the entire first layer 22 is formed from a hydrophobic material, while in other embodiments, at least one of the inner surfaces 28a, 28b, and 28c is coated with hydrophobic material. This may help reduce leaching, evaporation, diffusion and/or other transfer of the reagent or one of its components from the corresponding reservoir. When the reagent or the like is lyophilized, the hydrophobic material may help keep water, water vapor and/or other gases or liquids from entering the corresponding reservoir prior to use of the microfluidic cartridge 10″.
Likewise, and in the illustrative embodiment, the second layer 24 has inner surfaces 30a, 30b, and 30c facing the reservoirs 12a″, 12b″ and 12c″, respectively. Like above, and in some embodiments, at least one of the inner surfaces 30a, 30b, and 30c includes a hydrophobic material, such as a Polymonochlorotrifluoroethylene (PCTFE) homopolymer and/or copolymer. In some embodiments, the entire second layer 24 is formed from a hydrophobic material, while in other embodiments, at least one of the inner surfaces 30a, 30b, and 30c is coated with hydrophobic material. Again, this may further help reduce leaching, evaporation, diffusion and/or other transfer of the reagent or one of its components from the corresponding reservoir. When the reagent or the like is lyophilized, the hydrophobic material may help keep water, water vapor and/or other gases or liquids from entering the corresponding reservoir prior to use of the microfluidic cartridge 10″.
As noted above, and in the illustrative embodiment, the one or more intermediate layers 26 each include three apertures extending therethrough, which define the side walls of the reservoirs 12a″, 12b″ and 12c″. It is contemplated that, in some embodiments, at least some of the side walls 32a, 32b and 32c may includes a hydrophobic material, such as a Polymonochlorotrifluoroethylene (PCTFE) homopolymer and/or copolymer. In some embodiments, each of the one or more intermediate layers 26 is formed from a hydrophobic material, while in other embodiments, at least some of the side walls 32a, 32b and 32c are merely coated with hydrophobic material. The use of a hydrophobic material may further help reduce leaching, evaporation, diffusion and/or other transfer of the reagent or one of its components from the corresponding reservoir. When the reagent or the like is lyophilized, the hydrophobic material may also help keep water, water vapor and/or other gases or liquids from entering the corresponding reservoir prior to use of the microfluidic cartridge 10″.
In other embodiments, the hydrophobic material 40a, 40b and 40c may be provided in the form of an insert that is inserted into each of at least selected reservoirs 12a′″, 12b′″, and 12c′″. The inserts maybe adapted to store one or more reagent and/or other substances, and may be formed from, or coated with, a hydrophobic material such as a Polymonochlorotrifluoroethylene (PCTFE) homopolymer and/or copolymer.
In some embodiments, the inserts 40a, 40b and 40c are formed separately from the remainder of the fluidic cartridge 10′″, and provided in the appropriate reservoirs 12a′″, 12b′″, and 12c′″ before the first layer 22 is assembled with the second layer 24 and the one or more intermediate layers 26. The inserts 40a, 40b and 40c may include the desired reagent or other substance before they are inserted into the corresponding reservoirs 12a′″, 12b′″, and 12c′″. Alternatively, the inserts 40a, 40b and 40c may be filled after they are inserted into the corresponding reservoirs 12a′″, 12b′″, and 12c′″. In some cases, the inserts 40a, 40b and 40c are heated so they accept the shape of the corresponding reservoirs 12a′″, 12b′″, and 12c′″. The inserts may include an access channel or opening that, when opened, is in fluid communication with the corresponding channel 14a, 14b and 14c, as desired.
Like above, the illustrative microfluidic cartridge 50 includes three reservoirs 52a, 52b, and 52c. At least one of the reservoirs 52a, 52b and 52c may be adapted to accept and store a substance or material, such as a sample, a reagent, or any other suitable substance, for an extended period of time. The sample may be, for example, a blood sample. The reagent may be, for example, a lysing agent, a sheath fluid or any other suitable reagent or substance in liquid, gas or solid form, as desired.
In the illustrative embodiment, each reservoir 52a, 52b and 52c includes a channel 54a, 54b and 54c, respectively. The channels 54a, 54b and 54c may be used to deliver the sample, reagent, and/or any other suitable substance from the corresponding reservoirs 52a, 52b and 52c to a fluidic circuit or the like on the microfluidic cartridge 50. In the illustrative embodiment, the channels 54a, 54b and 54c are fluidly connected to downward extending ports 55a, 55b, and 55c, respectively, which delivery the fluid down to one or more micro channels in a fluidic circuit formed in or on one or more thin laminated layers (see below).
The fluidic circuit may be used to perform, for example, desired material analysis and/or manipulation functions, such as chemical, biological and/or physical analyses, including in some cases, cytometry. In some cases, and as shown in the illustrative embodiment of
In accordance with the illustrative embodiment, one or more of the reservoirs 52a, 52b and 52c may be adapted to store a reagent or other substance for an extended period of time, thus increasing the shelf life of the microfluidic cartridge 50. In one illustrative embodiment, this may be accomplished by making at least part of a wall of at least one of the reservoirs 52a, 52b and 52c from a hydrophobic material, such as a polymonochlorotrifluoroethylene (PCTFE) homopolymer and/or copolymer. The hydrophobic material may help reduce leaching, evaporation, diffusion and/or other transfer of the reagent or other substance, or one of its components, from the reservoir. When the reagent or other substance is lyophilized, the hydrophobic material may help keep water, water vapor and/or other gases or liquids from entering the reservoir prior to use of the microfluidic cartridge 50.
In some systems, such as flow cytometry systems, a fluid driving system drives a sample fluid and a number of supporting fluids or reagents from one or more of the reservoirs 52a, 52b and 52c into the fluidic circuit. The fluidic circuit may, for example, arrange the particles into single file, typically using hydrodynamic focusing. In accordance therewith, the illustrative microfluidic cartridge 50 shown in
In the illustrative embodiment, a thicker layer, with a less precise thickness is used to form the reservoirs 52a, 52b and 52c. In the illustrative embodiment, a reservoir forming layer 65 with a thickness of 3-4 mils is provided, and is adhered to the thin laminated layers 63. The reservoirs 52a′, 52b′ and 52c′ may be molded, laser cut, or formed in any other suitable manner in the reservoir forming layer 65, as desired.
In this illustrative embodiment, the reservoir forming layer 65, or at least the portion that includes the reservoirs 52a′, 52b′ and 52c′, is formed from a hydrophobic material 20 such as a polymonochlorotrifluoroethylene (PCTFE) homopolymer and/or copolymer. While PCTFE is believed to outperform many other materials, other illustrative materials may include, for example, a Poly-Vinylidene Dichloride (PVdC) homopolymer and/or copolymer, an ethylene chlorotrifluoroethylene copolymer, an ethylene tetrafluoroethylene copolymer, a fluorinated ethylene-propylene copolymer (FEP), a perfluoroalkoxy polymer (PFA), a polyvinylidene fluoride, a polyvinyl fluoride, a polyvinylidene chloride, a tetrafluoroethylene homopolymer and/or copolymer, a hexafluoropropylene homopolymer and/or copolymer, a vinylidene fluoride homopolymer and/or copolymer, or any other suitable hydrophilic material.
In the illustrative embodiment of
In the illustrative embodiment, the first layer 62 has inner surfaces 68a, 68b, and 68c facing reservoirs 52a″, 52b″ and 52c″, respectively. In some embodiments, at least one of the inner surfaces 68a, 68b, and 68c includes a hydrophobic material, such as a Polymonochlorotrifluoroethylene (PCTFE) homopolymer and/or copolymer. In some embodiments, the entire first layer 62 is formed from a hydrophobic material, while in other embodiments, at least one of the inner surfaces 68a, 68b, and 68c is coated with hydrophobic material. This may help reduce leaching, evaporation, diffusion and/or other transfer of the reagent or one of its components from the corresponding reservoir. When the reagent or the like is lyophilized, the hydrophobic material may help keep water, water vapor and/or other gases or liquids from entering the corresponding reservoir prior to use of the microfluidic cartridge 50″.
Likewise, the second layer 64 may have inner surfaces 70a, 70b, and 70c facing reservoirs 52a″, 52b″ and 52c″, respectively. Like above, and in some embodiments, at least one of the inner surfaces 70a, 70b, and 70c includes a hydrophobic material, such as a Polymonochlorotrifluoroethylene (PCTFE) homopolymer and/or copolymer. In some embodiments, the entire second layer 64 is formed from a hydrophobic material, while in other embodiments, at least one of the inner surfaces 70a, 70b, and 70c is coated with hydrophobic material. Again, this may further help reduce leaching, evaporation, diffusion and/or other transfer of the reagent or one of its components from the corresponding reservoir. When the reagent or the like is lyophilized, the hydrophobic material may help keep water, water vapor and/or other gases or liquids from entering the corresponding reservoir prior to use of the microfluidic cartridge 50″.
As noted above, and in the illustrative embodiment, the one or more intermediate layers 66 include three apertures extending therethrough, which define the side walls of the reservoirs 52a″, 52b″ and 52c″. It is contemplated that, in some embodiments, at least some of the side walls 72a, 72b and 72c include a hydrophobic material, such as a Polymonochlorotrifluoroethylene (PCTFE) homopolymer and/or copolymer. In some embodiments, each of the one or more intermediate layers 66 is formed from a hydrophobic material, while in other embodiments, at least part of the side walls 72a, 72b and 72c is coated with hydrophobic material. This may further help reduce leaching, evaporation, diffusion and/or other transfer of the reagent or one of its components from the corresponding reservoir. When the reagent or the like is lyophilized, the hydrophobic material may also help keep water, water vapor and/or other gases or liquids from entering the corresponding reservoir prior to use of the microfluidic cartridge 50″.
In other embodiments, the hydrophobic material 80a, 80b and 80c may be provided in the form of inserts that are inserted into at least selected reservoirs 52a′″, 52b′″, and 52c′″. The inserts may be adapted to store one or more reagent and/or other substances, and may be formed from, or coated with, a hydrophobic material such as a Polymonochlorotrifluoroethylene (PCTFE) homopolymer and/or copolymer.
In some embodiments, the inserts 80a, 80b and 80c are formed separately from the remainder of the fluidic cartridge 50′″, and provided in the appropriate reservoirs 52a′″, 52b′″, and 52c′″ before the first layer 62 is assembled with the second layer 64 and the one or more intermediate layers 66. The inserts 80a, 80b and 80c may include the desired reagent or other substance before they are inserted into the corresponding reservoirs 52a′″, 52b′″, and 52c′″. Alternatively, the inserts 80a, 80b and 80c may be filled after they are provided in the corresponding reservoirs 52a′″, 52b′″, and 52c′″. In some cases, the inserts 80a, 80b and 80c are heated so they accept the shape of the corresponding reservoirs 52a′″, 52b′″, and 52c′″, and/or may be in the form of blister packs. The inserts may include or be adapted to include an access channel or opening that, when opened, is in fluid communication with the corresponding channel 54a, 54b and 54c, if desired.
As shown in
A light source and associated optics generally shown at 94 may be positioned adjacent to the one or more thin laminated layers 63″, as shown. Because the one or more thin laminated layers 63 may have relatively controlled thicknesses, the vertical position of the focusing channel 59 to the light source 94 can be controlled. This may help the light source and associated optics 94 focus the light onto the focusing channel 59, if desired. In the illustrative embodiment, one or more light detectors (and sometimes associated optics) may be positioned above the focusing channel 59 to receive light signals, sometimes including light scatter, through the focusing channel 59. This may help identify certain characteristics of the material flowing through the focusing channel 59.
Having thus described the preferred embodiments of the present invention, those of skill in the art will readily appreciate that the teachings found herein may be applied to yet other embodiments within the scope of the claims hereto attached.
