Patent Publication Number: US-9901925-B2

Title: Micro-fluidic device

Description:
RELATED APPLICATIONS 
     This application is a Continuation of U.S. patent application Ser. No. 14/986,462 entitled MICRO-FLUIDIC DEVICE, filed Dec. 31, 2015, which is a Continuation of U.S. patent application Ser. No. 14/619,791 entitled MICRO-FLUIDIC DEVICE, filed Feb. 11, 2015, which is a Continuation of U.S. patent application Ser. No. 14/224,548 entitled MICRO-FLUIDIC DEVICE, filed Mar. 25, 2014, and issued as U.S. Pat. No. 8,980,199, on Mar. 17, 2015, which is a Continuation of U.S. patent application Ser. No. 13/858,678 entitled MICRO-FLUIDIC DEVICE, filed Apr. 8, 2013, and issued as U.S. Pat. No. 8,709,357 on Apr. 29, 2014, which is a Continuation of U.S. patent application Ser. No. 13/448,235 entitled MICRO-FLUIDIC DEVICE, filed Apr. 16, 2012 and issued as U.S. Pat. No. 8,414,849 on Apr. 9, 2013, which is a Continuation of U.S. patent application Ser. No. 12/541,797 entitled MICRO-FLUIDIC DEVICE, filed Aug. 14, 2009 and issued as U.S. Pat. No. 8,158,082 on Apr. 17, 2012, which claims the benefit of Provisional U.S. Patent Application No. 61/093,283, entitled MICRO-FLUIDIC DEVICE, filed Aug. 29, 2008; all of the aforementioned priority applications being hereby incorporated by reference in their respective entirety for all purposes. 
    
    
     BACKGROUND 
     Field of the Invention 
     Embodiments described herein relate to micro-fluidic devices. More specifically, embodiments relate to micro-fluidic devices having a bubble jet pump. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a perspective view illustrating an embodiment of a micro-fluidic device including a bubble jet based pump. 
         FIG. 2  is a schematic view illustrating an embodiment of a micro-fluidic circuit including a bubble jet based pump. 
         FIG. 3  is a schematic view illustrating another embodiment of a micro-fluidic circuit including a bubble jet based pump, controller and other components. 
         FIG. 4  is a schematic view illustrating another embodiment of a micro-fluidic circuit including a bubble jet based pump that is configured to be coupled to an external analytical device. 
     
    
    
     DETAILED DESCRIPTION 
     Embodiments described herein provide micro-fluidic systems and devices for use in performing various diagnostic tests. Many embodiments employ a bubble jet based pump as a mechanism for precisely controlling the flow of fluids within the device, including the introduction of fluids into one or more reaction chambers disposed within the device. Such embodiments allow for the precise control of: (i) the introduction of a sample fluid into a reaction chamber, and/or (ii) sequenced or timed introduction of one or more reactants for the sample fluid to allow for a chemical reaction to occur in the chamber. Such chemical reactions can be used to perform medical diagnostic tests or assays, including those used for colorometric assays and immunoassays including enzyme-linked immunosorbent assay (ELISA) and other immuno-based assays known in the art. 
     Embodiments described herein provide micro-fluidic systems and devices for use in performing various diagnostic tests. Embodiments of the device can include one or more chambers to enable receiving and reaction of fluid samples used in performing a diagnostic test. According to one embodiment, the micro-fluidic device includes a sample chamber for receiving a sample, and a reaction chamber for performing a chemical reaction. A bubble jet pump is structured on the device to control delivery of a fluid from the sample chamber to the reaction chamber. The pump is fluidically coupled to one or more chambers of the device using a fluidic channel such as a capillary. A valve may also be coupled to one or more chambers to control flow into and out of those chambers. Additionally, a sensor may be positioned in one or more of the chambers, such as the reactant chamber, for sensing a property of the fluid within the chamber as well as the presence of a chemical within the chamber. 
     Further details of these and other embodiments of micro-fluidic systems and devices are described more fully below with reference to the attached figures. 
     Referring now to  FIGS. 1-4 , an embodiment of a micro-fluidic device  10  can include one or more micro-fluidic features  11  for performing one or more functions on the device. Such features  11  can include fluidic channels  20 , ports  22 , a sample chamber  30  (which may containing a test sample  31 ), one or more reactant chambers  40  containing one or more reactants  41 ,  42 ,  43 , a pump  70  and a collection chamber  80  for collection of fluid  81 . Fluidic channels  20  provide a pathway on the micro-fluidic device  10  in which a fluid can flow between or among various chambers, pumps, ports and other features  11  on the micro-fluidic device  10 . One or more features  11  can be arranged to form a micro-fluidic circuit  15 .  FIG. 2  illustrates an embodiment of a micro-fluidic circuit  15 . Other arrangements or configurations for micro-fluidic circuits  15  may also be provided. 
     Micro-fluidic device  10 , including one or more features  11 , can be formed on a variety of substrates including silicon as well as polymer based substrates using etching and/or lithographic processes known in the art. Suitable polymers include elastomeric polymers such as silicone. Typically, micro-fluidic device  10  will comprise a micro-fluidic chip  10 C that is configured to engage or otherwise be coupled to one or more medical diagnostic or analytical instruments. However, other micro-fluidic devices are also contemplated. For example, micro-fluidic device  10  can comprise a micro-fluidic column or other separation device that mates with a medical diagnostic or analytical instrument. Alternatively, micro-fluidic device  10  can be a stand alone device such as a lab-on-a-chip that needs no external connections and can even include its own power source, such as a miniature lithium battery (e.g., a button battery) or other miniature battery. 
     Ports  22  are coupled to channels  20  and provide a pathway for the flow of fluid in and/or out of micro-fluidic device  10 . Typically, micro-fluidic device  10  will include at least one inlet and outlet port  22 , but can have one or the other, or none. Multiple inlet and outlet ports  22  are also contemplated to allow for the inflow and outflow of multiple fluids and/or parallel fluid flow of the same or different fluids. 
     In one embodiment, channels  20  can include one or more valves  50  to control the flow of fluid into and out of various chambers and other features  11  on the micro-fluidic device  10 , as well as the direction  21  of fluid flow. Valves  50  can also be positioned at or integral to chambers  30 ,  40 ,  60  and  80 , as well as pump  70 . They can also be positioned at ports  22 . In various embodiments, valves  50  can comprise one or more of an electronically, pneumatically, pressure or magnetically actuatable valve. Valves  50  can be one-way or two-way, and can be controlled electronically by means of a controller  90 , such as a microprocessor. In one embodiment, a valve  50  can comprise a pressure operated check valve. The cracking pressure of the valve  50  can be selected for the particular pressure generated by pump  70 . 
     In many embodiments, pump  70  comprises a bubble jet pump device  71 . In one embodiment, the bubble jet pump device  71  includes a heating element  72  that is used to controllably heat liquid within the pump chamber  73  to form a vapor bubble  74  which forces out a jet of a fixed volume of liquid  75 . Bubble jet pump device  71  can be similar to ink jet/bubble jet devices used in ink jet printers. However, according to one or more embodiments, bubble jet pump device  71  is adapted to function as a vacuum pump to controllably pull in a selected volume of fluid into reaction chamber  60  or other feature  11 , rather than eject or deposit fluid onto a surface. Heating element  72  can comprise a resistive/joulean heating element, but other heating elements are also contemplated including, RF, microwave, acoustic, infrared and gas elements. The ejected volume of liquid  75  (also known as drop size  75 ) creates vacuum pressure which pulls a fixed volume of fluid  76  from reaction chamber  60  and in turn, a fluid volume  77  drawn into the chamber from either sample chamber  30 , reactant chamber  40  or other feature  11 . The volume of drawn fluid  77  can be controlled by controlling the drop size  75 . The drop size  75  can be controlled by using various methods known in the bubble jet arts including controlling one or more of the power, duration and duty cycle of heating from heating element  72 . Other methods of controlling drop size  75  are also contemplated. For example, drop size  75  can be controlled through use of control valve  50  alone or in combination with other methods described above. 
     In various embodiments, heating element  72  can include an overlying hydrogel or other water containing polymer layer such that the vapor bubble  74  is derived from a phase change of water contained in the hydrogel layer rather than from fluid within chamber  73 . In this way, fluid within chamber  73  is thermally shielded from direct contact with heating element  72  while still allowing for the ejection of fluid from pump chamber  73  and pump  71 . The hydrogel layer can be configured to have a sufficient amount of trapped water or an aqueous based solution to allow for multiple firings of pump  71 . 
     In the embodiment shown in  FIG. 2 , a single bubble jet pump  71  is shown to be coupled with reaction chamber  60 . However in various embodiments, multiple bubble jet pumps  71  may be used. For example, each reactant chamber  40  can have its own bubble jet pump  71  in order to simultaneously (or close to simultaneously) enable or cause mixing of test sample  31  and reactants  41  in the reaction chamber  60 . Other combination for connecting bubble jet pumps  71  to one or more features  11  are also contemplated. For example, bubble jet pump  71  can be coupled to an inlet port  22  to pull a sample fluid  31  into micro-fluidic device  10  from an external source. 
     In many embodiments, bubble jet pump(s)  71  including heating element  72  are electronically coupled to a controller  90 , which can either be a device resident controller  91  or an external controller  92  or both. Heating element  72  and/or controller  91  can also be configured to enable wireless communication capabilities with an external controller or monitoring device  92 , including RF communications, such as provided by standards such as BLUE TOOTH or WIRELESS USB. Controller  90  can comprise a microprocessor, a state device or analog control circuit. Controller  90  can also be coupled to one or more control valves  50  to control the sequence and timing of fluid delivery from sample chamber  30  and reactant chambers  40 . 
     In particular embodiments, bubble jet pump  71  is configured to pull a controlled volume of fluid  77  into reaction chamber  60  from one or more of sample chamber  30 , reactant chamber(s)  40  or other device feature  11 . The amount of fluid drawn is selectable using techniques described above or other techniques known in the art. In various embodiments, the volume of drawn fluid  76  can be controlled using controller  90 . Different controlled volumes  77  can be selected from sample chamber  30  and each reactant chamber  40 . Controller  90  can contain one or more algorithms  93  which include a group and sequence of selected volumes  77  that are pulled from chambers  30  and  40  or other feature  11  depending on an analytical test to be performed within reaction chamber  60 . Algorithms  93  can also include a sequence of valve operations for opening and closing control valves  50  to control the sequence of fluid delivered from chambers  30 ,  40  or other feature  11 . Algorithms  93  can be preprogrammed on controller  90  or can also be signaled to controller  90  from an external controller using RF or other signaling method. In various embodiments, resident controller  91  can incorporate an RF ID tag or like device  94  for communication with external controller  92 . RF ID tag  94  can also be a separate device that is positioned at selectable location on device  10 . 
     In one embodiment, reaction chamber  60  is configured to allow for the mixing of sample  31  with one or more chemical reactants  41  so as to have a chemical reaction take place in the chamber to produce a product solution  61 . Product solution  61  can have a particular property, such as a color, pH, etc., which allows for the detection and/or quantification of a particular analyte  32  in sample  30  (for example, a serum antibody such as the HIV antibody, or an analyte such as blood glucose, cholesterol (e.g., HDL, LDL), lipids, or a particular drug). In another embodiment, reactants  41  and reaction chamber  60  can be configured for performing a hematocrit or blood iron concentration test using analytical methods known in the art (e.g., a serum ferritin test as known in the art). Accordingly, in various embodiments, reaction chamber  60  can include one or more sensors  100  to allow for the detection/quantification of product solution  61 , including solutions for measuring hematocrit and/or blood iron. The sensor  100  can be an optical sensor including a detector and emitter for doing various spectrometric measurements of solution  61 . The emitter can use wavelengths configured to produce fluorescence in solution  61  (for example, to allow for the detection of an antibody containing a fluorescent compound or the presence of the heme molecule in blood). The emitter and detector can also be configured for performing various reflectance and absorbance measurements known in the art for detecting colorometric reactions in solution  61 , such as those used for the detection of blood glucose. In such embodiments, the emitter and detector can be offset a selectable distance and angle to allow for reflectance and/or absorbance measurement. In other embodiments, sensor  100  can be a pH sensor, temperature sensor, gas (e.g., O 2 ) sensor, flow sensor or other sensor known in the sensor art. Multiple sensors  100  can also be employed and placed in multiple locations in reaction chamber  60 , reactant chamber  40  or in other features  11  to allow for multiple measurements in multiple locations on device  10 . Embodiments having multiple sensors  100  can allow for improved real time control of the tests performed by device  10 . 
     In one embodiment, sensor  100  is configured to send a signal or input  110  to controller  90  (e.g., either controller  91  or  92 ), which can be used for detection and/or quantification of analyte  32 . In addition, Signal  110  can be used for monitoring the progress of the chemical reaction in reaction chamber  60 . Signal  110  can also be used by controller  90  to control the sequence of the introduction of sample, reactant and other fluids into and out of reaction chamber  60  or other features  11 . In particular embodiments, signal  110  is used to control the actuation of bubble jet pump(s)  71 . 
     In other embodiments, micro-fluidic device  10  can be configured to be coupled to an external analytical device  120 , such as a spectrophotometer, which generates a detection peak or waveform characteristic  130  of a particular analyte  32 . Coupling the external device  120  to device  10  can be achieved through the use of port  22  and/or valve  50 . 
     Embodiments of the micro-fluidic device  10  can be used in conjunction with a variety of systems. These systems can include a variety of micro-fluidic systems including, without limitation, micro-fluidic chips, micro-fluidic lab-on-chip devices, ELISA devices, electrophoresis devices, chromatography devices, micro-arrays, micro-fluidic columns and other like devices. 
     In various embodiments of methods of using device  10 , one or more of sample chamber  30 , reaction chamber  60  and connecting channels  20  can initially contain air. Also, reactant chambers  40  can be pre-primed with reactants  41 , or reactants  41  can be added to the reactant chambers  40  (e.g., by using an automated device). The user can also add sample  31  to sample chamber  30  by using a pipette or a similar device, or enable sample  31  to be added to the sample chamber  30  by using an automated device. When pump  71  is first actuated, it serves to evacuate all of the air from the connecting channel  20  and reaction chamber  60 , and draw in a fixed amount of fluid sample  31  from the sample chamber  30 . This allows reaction chamber  60  to be kept in a dry condition (in such embodiments, reaction chamber  60  may contain one or more dry reactants  40 ). A control valve  50  connecting the reaction chamber  60  with the sample chamber  30  can then be closed, and another control valve  50  can be opened to connect the reaction chamber  60  to a reactant chamber  40  that contains a reservoir of chemical reactant  41  (such as an antibody or enzyme). The pump  70  is then actuated again, thereby drawing in a fixed amount of reactant  41 . This process can then be continued with one or more other reactant reservoir chambers with the volume and time sequence of each added reactant being controlled via the bubble jet pump and a signal from the controller. Different volumes can be selected for different reactants with a fixed time interval between additions to allow for mixing and subsequent chemical reaction in the reaction chamber. 
     The reaction chamber  60  can be configured to perform various diagnostic tests such as ELISA (or other antibody based test) or a blood iron concentration test, such as a serum ferritin test. Also, the reaction chamber  60  can include various optical emitters and detectors (such a photomultiplier tube) to detect the presence of one or more products from the chemical reaction using spectro-photometric methods known in the art. 
     The foregoing description of various embodiments of the invention has been presented for purposes of illustration and description. It is not intended to limit the invention to the precise forms disclosed. Many modifications, variations and refinements will be apparent to practitioners skilled in the art. For example, the micro-fluidic device can have multiple reaction chambers with multiple bubble jet pumps allowing for the performance of multiple tests one device. Also, the micro-fluidic device can be constructed in a modular fashion to allow particular features to be selected and assembled by the user. 
     Elements, characteristics, or acts from one embodiment can be readily recombined or substituted with one or more elements, characteristics or acts from other embodiments to form numerous additional embodiments within the scope of the invention. Moreover, elements that are shown or described as being combined with other elements, can, in various embodiments, exist as standalone elements. Hence, the scope of the present invention is not limited to the specifics of the described embodiments, but is instead limited solely by the appended claims.