Microfluidic Systems, Apparatuses, and Cartridges Including Self-Aligning Optical Fiber Systems and Methods - Patent application

Abstract

The present invention is directed to microfluidic systems, instruments, and cartridges that include self-aligning fiber optic systems and methods of their use.

Description

[Technical field]

[0001] FIELD OF THE DISCLOSURE Generally, the presently disclosed subject matter relates to fiber optic interfaces, and more particularly, to microfluidic systems, devices, and cartridges that include self-aligning fiber optic systems and methods.

[0002] (Related Applications) The presently disclosed subject matter is related to and claims priority to U.S. Provisional Patent Application No. US63 / 193,944, filed May 27, 2021, and entitled "Microfluidics Instrument and Cartridge Including an Optical Fiber Alignment Mechanism," and U.S. Provisional Patent Application No. US63 / 237,868, filed August 27, 2021, and entitled "Microfluidics System, Instrument, and Cartridge Including Self-Aligning Optical Fiber System and Method," the entire disclosures of which are incorporated herein by reference. [Background technology]

[0003] In applications requiring an optical coupling between two systems, devices, and / or components, it can be difficult to achieve the optical coupling in a simple and automated manner. For example, a typical fiber optic coupler is a single connector that is manually operated or has screw terminals to make the connection.

[0004] In microfluidic applications, for example, optical coupling may be required between a microfluidic instrument and a microfluidic device (or cartridge). In this example, a limitation is that optical fibers may be manually connected to the microfluidic device (or cartridge) one at a time. Furthermore, the number of optical connections may be limited. Another limitation is that the mechanical complexity of the optical coupling may reside primarily on the microfluidic device (or cartridge) side of the system, with little or no complexity on the microfluidic instrument side of the system. Thus, new approaches are needed for optical coupling between two systems, devices, and / or components. Summary of the Invention

[0005] In some aspects, the present invention is directed to a microfluidic system comprising: (a) a microfluidic device, the microfluidic device including an optical detection system; (b) a microfluidic cartridge; and (c) a self-aligning optical fiber system optically coupling the microfluidic device and the microfluidic cartridge. In some embodiments, the optical detection system comprises an illumination source and an optical measurement device.

[0006] In some embodiments, the microfluidic system includes a self-aligning fiber optic system including an instrument fiber optic coupler and a cartridge fiber optic connector. In some embodiments, the self-aligning fiber optic system includes a plurality of optical detection channels, each of the plurality of optical detection channels including an instrument optical channel and a cartridge optical channel. In one embodiment, the self-aligning fiber optic system includes about 4 to about 16 optical detection channels. In one embodiment, each of the instrument optical channels optically connects each of the cartridge optical channels to an optical measurement device.

[0007] In some embodiments, the instrument fiber optic coupler includes a plurality of instrument ferrule assemblies each including a tip and an instrument optical fiber. In some embodiments, the cartridge optical fiber connector further includes a plurality of cartridge ferrule assemblies each including a receiving end capable of receiving an instrument ferrule assembly and each including a cartridge optical fiber.

[0008] In some embodiments, the microfluidic device further includes a movable slide mechanism operable to create an optical coupling between the microfluidic device and the microfluidic cartridge by engaging the instrument fiber optic coupler with the cartridge fiber optic connector. In other embodiments, the movable slide mechanism is operable to engage the instrument ferrule assembly with the cartridge ferrule assembly, thereby coupling the instrument optical fiber to the cartridge optical fiber. In yet other embodiments, the movable slide mechanism includes a slidable base plate attached to the rails, a backplate attached to an end of the slidable base plate, and a lead screw and associated motor operable to advance and / or retract the instrument optical fiber coupler relative to the cartridge optical fiber connector.

[0009] In one embodiment, the microfluidic cartridge further comprises (a) a bottom substrate, the bottom substrate comprising a droplet operations surface, and (b) a top substrate, the bottom substrate and the top substrate being separated by a droplet operations gap therebetween. In some embodiments, the microfluidic cartridge is a digital microfluidic cartridge (DMF). In some embodiments, the bottom substrate and / or the top substrate comprise a PCB substrate, a glass substrate, or a silicon substrate, the PCB substrate, the glass substrate, or the silicon substrate being optionally coated with a dielectric layer and one or more electrodes operable for droplet operations.

[0010] In some embodiments, the droplet operations gap between the bottom substrate and the top substrate is filled with a filler fluid, hi one embodiment, the filler fluid is a low viscosity oil or a halogenated oil.

[0011] In some embodiments, the optical detection system includes one or more surface plasmon resonance (SPR) sensors or one or more localized surface plasmon resonance (LSPR) sensors.

[0012] According to another aspect, the invention is directed to a method for performing an optical detection operation, the method including: (a) providing a microfluidic system including a microfluidic device, a microfluidic cartridge, and a plurality of optical detection channels, (i) the microfluidic device including an instrument fiber optic coupler, and (ii) the microfluidic cartridge including a cartridge fiber optic connector; (b) performing a first optical alignment step of aligning the instrument fiber optic coupler to the cartridge fiber optic connector; (c) performing a second optical alignment step of individually aligning each optical detection channel; and (d) performing an optical detection operation using the microfluidic system, the microfluidic device, and the microfluidic cartridge.

[0013] In one embodiment, the microfluidic device further includes a movable slide mechanism, and the first optical alignment step is performed by moving the movable slide mechanism until the fiber optic coupler engages the fiber optic connector. In one embodiment, the fiber optic coupler is moved toward the fixed fiber optic connector. In some embodiments, the first optical alignment step results in course alignment of each of the multiple optical detection channels.

[0014] In one embodiment, the second optical alignment step provides fine alignment of each of the multiple optical detection channels. In some embodiments, the second alignment step is performed by continuing to translate the movable slide mechanism toward the microfluidic cartridge until the fiber optic coupler fully engages the fiber optic connector, thereby individually aligning each of the optical detection channels.

[0015] In some embodiments, the fiber optic coupler further includes a plurality of instrument ferrule assemblies each including a tip and an instrument optical fiber, the fiber optic connector further includes a plurality of cartridge ferrule assemblies each including a receiving end capable of receiving an instrument ferrule assembly and each including a cartridge optical fiber, and the movable slide is moved until each of the instrument ferrule assemblies engages each of the cartridge ferrule assemblies, thereby connecting the instrument optical fiber with the cartridge optical fiber and generating a plurality of optical detection channels. In other embodiments, the instrument fiber optic coupler further includes a housing having one or more dowel pins, and the cartridge optical connector further includes a housing having one or more datum holes, the one or more datum holes receiving the one or more dowel pins during the first alignment step. In one embodiment, the dowel pins align the instrument fiber optic coupler to the cartridge optical fiber connector.

[0016] In one embodiment, the second alignment step provides Z-alignment between the fiber optic coupler and the fiber optic connector. In another embodiment, the second alignment step provides Z-alignment between each of the instrument ferrule assemblies and each of the cartridge ferrule assemblies to align the instrument optical fiber and the cartridge optical fiber in opposition with substantially no gap therebetween. In yet another embodiment, the instrument ferrule assemblies further include a spring, which aligns the instrument optical fiber and the cartridge optical fiber in opposition with substantially no gap therebetween.

[0017] In one embodiment, the instrument optical fiber is aligned to within about ±0.7 mm of the cartridge optical fiber. In another embodiment, the instrument optical fiber is aligned to within about ±50 μm of the cartridge optical fiber. In some embodiments, an optical gel is applied between the instrument optical fiber and the cartridge optical fiber.

[0018] In some embodiments, the microfluidic system further comprises an optical detection system including an illumination source and an optical measurement device. In other embodiments, the optical detection system comprises surface plasmon resonance (SPR) or localized surface plasmon resonance (LSPR), and the optical detection system comprises an SPR or LSPR illumination source and one or more SPR or LSPR optical measurement devices. In yet other embodiments, the microfluidic cartridge is a digital microfluidic cartridge (DMF). [Brief description of the drawings]

[0019] The features and advantages of the present invention will be more clearly understood from the following description considered in conjunction with the accompanying drawings, which are not necessarily drawn to scale. [Figure 1] FIG. 1 shows a block diagram of a microfluidic system that includes one embodiment of the presently disclosed self-aligning optical fiber system for optically coupling a microfluidic instrument to a microfluidic device (or cartridge). [Figure 2A] FIG. 2A shows a perspective view of an exemplary instantiation of a microfluidic system including a microfluidic device optically coupled to a microfluidic device (or cartridge) using the presently disclosed self-aligning optical fiber system shown in FIG. [Figure 2B] FIG. 2B shows a perspective view of one embodiment of the microfluidic device portion of the microfluidic system shown in FIG. [Diagram 3] FIG. 3 illustrates a perspective view of one embodiment of the presently disclosed self-aligning fiber optic system shown in FIGS. 1 and 2 and including an instrument fiber optic coupler and a cartridge fiber optic connector. [Figure 4] FIG. 4 illustrates a perspective view of one embodiment of the presently disclosed self-aligning fiber optic system shown in FIGS. 1 and 2 and including an instrument fiber optic coupler and a cartridge fiber optic connector. [Diagram 5] FIG. 5 illustrates a perspective view of one embodiment of the presently disclosed self-aligning fiber optic system shown in FIGS. 1 and 2 and including an instrument fiber optic coupler and a cartridge fiber optic connector. [Figure 6] FIG. 6 illustrates a perspective view showing further details of the presently disclosed self-aligning optical fiber system shown in FIGS. 1-5. [Figure 7] 7A and 7B show perspective and exploded views, respectively, of one embodiment of an instrument ferrule assembly of the instrument fiber optic coupler shown in FIGS. [Figure 8] FIG. 8 shows various views illustrating further details of one embodiment of an instrument ferrule of the instrument ferrule assembly shown in FIG. 7A. [Figure 9] 9A and 9B show other perspective views of the instrument ferrule assembly shown in FIG. 7A. [Figure 10] FIG. 10 shows a side view of the instrument ferrule assembly shown in FIG. 7A. [Figure 11] 11A and 11B show front and rear views, respectively, of the instrument ferrule assembly shown in FIG. 7A. [Figure 12] FIG. 12 shows perspective views of the instrument ferrule shown in FIG. 7A in various assembly states. [Figure 13] FIG. 13 shows a perspective view and an exploded view, respectively, of one embodiment of an instrument fiber optic coupler for the presently disclosed self-aligning fiber optic system shown in FIGS. 1-6. [Figure 14] FIG. 14 shows a perspective view and an exploded view, respectively, of one embodiment of an instrument fiber optic coupler for the presently disclosed self-aligning fiber optic system shown in FIGS. 1-6. [Figure 15A] FIG. 15A illustrates a perspective view of one embodiment of a cartridge ferrule assembly of a cartridge fiber optic connector of the presently disclosed self-aligning fiber optic system shown in FIGS. 1-6. [Figure 15B] FIG. 15B shows a perspective cross-sectional view of the cartridge ferrule assembly shown in FIG. 15A. [Figure 16] 16A and 16B show top and side views, respectively, of the cartridge ferrule assembly shown in FIG. 15A. [Figure 17] 17A and 17B show front and rear views, respectively, of the cartridge ferrule assembly shown in FIG. 15A. [Figure 18] FIG. 18 shows an exploded view of the cartridge ferrule assembly shown in FIG. 15A. [Figure 19] FIG. 19 illustrates a cross-sectional view showing further details of one embodiment of a cartridge ferrule of the cartridge ferrule assembly shown in FIG. 15A. [Figure 20] FIG. 20 illustrates a cross-sectional view of a portion of the presently disclosed self-aligning fiber optic system shown in FIGS. 1-6, showing the instrument fiber optic coupler and the cartridge fiber optic connector fully engaged together. [Figure 21]FIG. 21 illustrates a cross-sectional view of a portion of the presently disclosed self-aligning fiber optic system shown in FIGS. 1-6, showing the instrument fiber optic coupler and the cartridge fiber optic connector fully engaged together. [Figure 22] FIG. 22 illustrates a top view of an instrument fiber optic coupler for the cartridge fiber optic connector of the presently disclosed self-aligning fiber optic system shown in FIGS. 1-6. [Figure 23] FIG. 23 illustrates a top view of an instrument fiber optic coupler for the cartridge fiber optic connector of the presently disclosed self-aligning fiber optic system shown in FIGS. 1-6. [Figure 24] FIG. 24 illustrates a bottom view of an instrument fiber optic coupler for the cartridge fiber optic connector of the presently disclosed self-aligning fiber optic system shown in FIGS. 1-6. [Diagram 25] FIG. 25 illustrates a bottom view of an instrument fiber optic coupler for the cartridge fiber optic connector of the presently disclosed self-aligning fiber optic system shown in FIGS. 1-6. [Figure 26] FIG. 26 shows a flow diagram of one embodiment of a method of use of the presently disclosed microfluidic system including the self-aligning fiber optic system shown in FIGS. 1-25.

[0020] (definition) With respect to one or more electrodes, "activate" means to affect a change in the electrical state of one or more electrodes in the presence of a droplet, resulting in droplet operations. Activation of the electrodes may be accomplished using alternating current (AC) or direct current (DC). Any suitable voltage may be used. For example, the electrodes may be activated using a voltage greater than about 5 V, or greater than about 20 V, or greater than about 40 V, or greater than about 100 V, or greater than about 200 V, or greater than about 300 V. The appropriate voltage is a function of the properties of the dielectric, such as thickness and dielectric constant, the properties of the liquid, such as viscosity, as well as many other factors. If an AC signal is used, any suitable frequency may be employed. For example, the electrodes may be activated using an AC signal having a frequency of about 1 Hz-about 10 MHz, or about 1 Hz-about 10 KHz, or about 10 Hz-about 240 Hz, or about 60 Hz.

[0021] "Droplet" refers to a volume of liquid on a droplet actuator. Typically, a droplet is at least partially surrounded by a filler fluid. For example, a droplet may be completely surrounded by a filler fluid, or may be surrounded by a filler fluid and one or more surfaces of the droplet actuator. As another example, a droplet may be surrounded by a filler fluid, one or more surfaces of the droplet actuator, and / or the atmosphere. As yet another example, a droplet may be surrounded by a filler fluid and the atmosphere. A droplet may be, for example, aqueous or non-aqueous, or may be a mixture or emulsion including aqueous and non-aqueous components.

[0022] "Droplet actuator" refers to a device for manipulating droplets. Microfluidic devices, microfluidic cartridges, digital microfluidic (DMF) devices, and DMF cartridges are examples of droplet actuators. A particular droplet actuator may include one or more substrates disposed with a droplet operations gap therebetween, and electrodes associated with (e.g., patterned, laminated, attached, and / or embedded in) the one or more substrates and arranged to perform one or more droplet operations. For example, a particular droplet actuator may include a base (or bottom) substrate, droplet operations electrodes associated with the substrates, one or more dielectric layers on the substrates and / or electrodes, and optionally one or more hydrophobic layers on the substrates, dielectric layers, and / or electrodes that form a droplet operations surface. A top substrate may also be provided that is separated from the droplet operations surface by a gap, commonly referred to as the droplet operations gap. A droplet actuator may include various electrode arrangements on the top and / or bottom substrates. During droplet operations, the droplets preferably remain in continuous or frequent contact with a ground or reference electrode. The ground or reference electrode may be associated with the top substrate facing the gap, the bottom substrate facing the gap, or within the gap itself. If electrodes are provided on both substrates, electrical contacts for coupling the electrodes to droplet actuator equipment for controlling or monitoring the electrodes may be associated with one or both plates. In some cases, the electrodes on one substrate are electrically coupled to the other substrate, and only one substrate is in contact with the droplet actuator. If multiple substrates are used, spacers may be provided between the substrates to determine the height of the gap between them and define the dispense reservoir on the actuator. The height of the spacer may be, for example, about 5 μm to about 1000 μm, or about 100 μm to about 400 μm, or about 200 μm to about 350 μm, or about 250 μm to about 300 μm, or about 275 μm. The spacers may be formed, for example, of features or layers protruding from the upper or lower substrate and / or material interposed between the upper and lower substrates. One or more openings may be provided in one or more of the substrates to form a fluid pathway through which liquid may be supplied to the droplet operations gap.

[0023] In some cases, the top and / or bottom substrate of the droplet actuator comprises a PCB substrate that is coated with a dielectric, such as a polyimide dielectric, and in some cases the PCB substrate may also be coated or otherwise treated to render the droplet operation surface hydrophobic. A variety of materials are also suitable for use as the dielectric component of the droplet actuator. In some cases, the top and / or bottom substrate of the droplet actuator comprises a glass or silicon substrate in which features have been patterned using process techniques borrowed from semiconductor device manufacturing, including the deposition and etching of thin layers of materials using microlithography. The top and / or bottom substrate may comprise a semiconductor backplane (i.e., a thin film transistor (TFT) active matrix controller) on which the droplet operation electrodes are formed.

[0024] Typically, the electrodes of the droplet actuator are controlled by a controller or processor, which itself is provided as part of a system and may include processing capabilities, as well as data and software storage, and input / output capabilities. Reagents may be provided on the droplet actuator in the droplet operations gap or in a reservoir fluidically coupled to the droplet operations gap. Reagents may be in liquid form, e.g., droplets, or may be provided in a reconstitutable form in the droplet operations gap or in a reservoir fluidically coupled to the droplet operations gap. Typically, reconstitutable reagents may be combined with a liquid for reconstitution.

[0025] "Droplet operations" refers to any manipulation of droplets on a droplet actuator. Droplet operations may include, for example, loading a droplet onto a droplet actuator; dispensing one or more droplets from a source droplet; splitting, separating, or dividing a droplet into two or more droplets; transporting a droplet from one location to another in any direction; merging or combining two or more droplets into a single droplet; thinning a droplet; mixing a droplet; agitating a droplet; deforming a droplet; holding a droplet in place; incubating a droplet; heating a droplet; evaporating a droplet; cooling a droplet; disposing of a droplet; transporting a droplet off of a droplet actuator; other droplet operations described herein; and / or any combination of the foregoing. The terms "merge," "merging," "combining," "combining," and the like are used to describe the generation of one droplet from two or more droplets. When such terms are used in connection with two or more droplets, it should be understood that any combination of droplet operations sufficient to result in the combination of the two or more droplets into one droplet may be used. For example, "merging droplet A with droplet B" may be accomplished by transporting droplet A in contact with immobilized droplet B, transporting droplet B in contact with immobilized droplet A, or transporting droplets A and B in contact with each other. The terms "separating," "separating," and "dividing" are not intended to imply any particular outcome with respect to the volume of the resulting droplets (i.e., the volume of the resulting droplets may be the same or different) or the number of resulting droplets (the number of resulting droplets may be 2, 3, 4, 5, or more). The term "mixing" refers to a droplet operation that results in a more uniform distribution of one or more components within the droplets. Examples of "loading" droplet operations include microdialysis loading, pressure assisted loading, robotic loading, passive loading, and pipette loading.Droplet operations may be electrode-mediated. In some cases, droplet operations are further facilitated by the use of hydrophilic and / or hydrophobic regions on the surface and / or by physical obstacles. For examples of droplet operations, see the patents and patent applications cited above under the definition of "droplet actuator." Sometimes, impedance and / or capacitance sensing and / or imaging techniques may be used to determine or confirm the results of droplet operations. Generally, sensing or imaging techniques may be used to confirm the presence or absence of a droplet at a particular electrode. For example, after a droplet dispensing operation, the presence of a dispensed droplet at a destination electrode confirms that the droplet dispensing operation was valid. Similarly, at an appropriate step in the assay protocol, the presence of a droplet at a detection spot may confirm that a previous series of droplet operations successfully produced a droplet for detection. Droplet transport times may be very fast. For example, in various embodiments, the transport of a droplet from one electrode to the next may be completed within about 1 second, or about 0.1 seconds, or about 0.01 seconds, or about 0.001 seconds. In one embodiment, the electrodes are operated in AC mode, but switched to DC mode for imaging. A droplet footprint area that is similar to or larger than the electrowetting area is useful for performing droplet operations. In other words, 1x-, 2x-, and 3x-droplets can be usefully controlled and / or manipulated using one, two, and three electrodes, respectively. If the droplet footprint is larger than the number of electrodes available to perform droplet operations at a given time, typically the difference between the droplet size and the number of electrodes should not be greater than one. In other words, 2x droplets are usefully controlled using one electrode, and 3x droplets are usefully controlled using two electrodes. When the droplets contain beads, it is useful for the droplet size to be equal to the number of electrodes that control the droplet, for example transporting the droplet.

[0026] "Filler fluid" means a fluid associated with a droplet operations substrate of a droplet actuator, the fluid being sufficiently immiscible with the droplet phase to subject the droplet phase to electrode-mediated droplet operations. For example, typically, the droplet operations gap of a droplet actuator is filled with a filler fluid. The filler fluid may be or include a low viscosity oil, such as, for example, silicone oil or hexadecane. The filler fluid may be or include a halogenated oil, such as a fluorinated oil or a perfluorinated oil. The filler fluid may fill the entire gap of the droplet actuator, or may only coat one or more surfaces of the droplet actuator. The filler fluid may be selected to improve droplet operations and / or reduce loss of reagents or target materials from droplets, reduce formation of unwanted microdroplets, reduce cross-contamination between droplets, reduce contamination of droplet actuator surfaces, reduce degradation of droplet actuator materials, reduce evaporation of droplets, etc. For example, the filler fluid may be selected for compatibility with the droplet actuator materials. As an example, fluorinated filler fluids may be usefully employed with fluorinated surface coatings. Fluorinated filler fluids are useful for reducing loss of lipophilic compounds, such as umbelliferone substrates, such as 6-hexadecanoylamido-4-methylumbelliferone substrate (e.g., for use in Krabbe, Niemann-Pick, or other assays). The filler fluid may be doped, for example, with surfactants or other additives. For example, additives may be selected to improve droplet manipulation and / or reduce loss of reagents or target substances from droplets, formation of microdroplets, cross-contamination between droplets, contamination of droplet actuator surfaces, degradation of droplet actuator materials, and the like. The composition of the filler fluid, including surfactant doping, may be selected for performance with reagents or samples used in a particular assay protocol, and effective interaction or non-interaction with the droplet actuator materials.For example, in some cases, the fluorinated oil may be doped with fluorinated surfactants, such as Zonyl FSO-100 (Sigma-Aldrich) and / or others.

[0027] The terms "top," "bottom," "over," "under," and "on" are used throughout the specification with reference to the relative positions of components of a droplet actuator, such as the relative positions of the top and bottom substrates of the droplet actuator. It will be understood that in many cases, the droplet actuator is functional regardless of its orientation in space.

[0028] When any form of liquid (e.g., droplet or continuum, moving or stationary) is described as being "on," "at," or "over" an electrode, array, matrix, or surface, such liquid may either be in direct contact with the electrode / array / matrix / surface, or may be in contact with one or more layers or membranes interposed between the liquid and the electrode / array / matrix / surface. In one embodiment, the filler fluid may be considered as a dynamic film between such liquid and the electrode / array / matrix / surface.

[0029] When a droplet is described as being "on" or "loaded on" a droplet actuator, it should be understood that the droplet is positioned on the droplet actuator in a manner that facilitates performing one or more droplet operations on the droplet using the droplet actuator, the droplet is positioned on the droplet actuator in a manner that facilitates sensing of a characteristic of or a signal from the droplet, and / or the droplet has undergone a droplet operation on the droplet actuator. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0030] The presently disclosed subject matter may now be more fully described below with reference to the accompanying drawings, in which some, but not all, embodiments of the presently disclosed subject matter are shown. Like numbers refer to like elements throughout. The presently disclosed subject matter may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein, but rather, these embodiments are provided so that this disclosure can satisfy applicable legal requirements. Indeed, many modifications and other embodiments of the presently disclosed subject matter described herein will come to mind to one skilled in the art to which the presently disclosed subject matter pertains having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. Therefore, it should be understood that the presently disclosed subject matter is not limited to the specific embodiments disclosed, and that modifications and other embodiments are intended to be included within the scope of the appended claims.

[0031] In some embodiments, the presently disclosed subject matter provides microfluidic systems, instruments, and cartridges that include self-aligning fiber optic systems and methods.

[0032] In some embodiments, the presently disclosed microfluidic systems, instruments, and cartridges, including self-aligning fiber optic systems and methods, provide a mechanism that enables interfacing between the microfluidic instrument and a disposable microfluidic device (or cartridge) that contains an embedded fiber optic sensor.

[0033] In some embodiments, the presently disclosed microfluidic systems, instruments, and cartridges, including self-aligning fiber optic systems and methods, provide an instrument fiber optic coupler on the microfluidic instrument side of the microfluidic system and a cartridge fiber optic connector on the microfluidic device (or cartridge) side of the microfluidic system.

[0034] In some embodiments, the presently disclosed microfluidic systems, instruments, and cartridges, including self-aligning fiber optic systems and methods, provide an instrument fiber optic coupler on the microfluidic instrument side of a microfluidic system and a cartridge fiber optic connector on the microfluidic device (or cartridge) side of the microfluidic system, ensuring a good optical fit (spacing less than about 10 um, concentricity tolerance less than about 100 um) therebetween.

[0035] In some embodiments, the presently disclosed microfluidic systems, instruments, and cartridges, including self-aligning fiber optic systems and methods, provide an instrument fiber optic coupler on the microfluidic instrument side of a microfluidic system and a cartridge fiber optic connector on the microfluidic device (or cartridge) side of the microfluidic system, ensuring a good optical fit between them, allowing for easy manufacturing tolerances of disposable microfluidic devices over significant distances, and enabling high volume manufacturing.

[0036] In some embodiments, the presently disclosed microfluidic systems, devices, and cartridges, including the self-aligning fiber optic systems and methods, provide a device fiber optic coupler on the microfluidic device side of the microfluidic system and a cartridge fiber optic connector on the microfluidic device (or cartridge) side of the microfluidic system, and the self-aligning fiber optic system may support any number of optical detection channels, such as, but not limited to, sixteen (16) optical detection channels. In general, any number of optical detection channels may be used. For example, in some embodiments, the self-aligning fiber optic system may include about four (4) to about sixteen (16), about four (4) to about fourteen (14), or about six (6) to about twelve (12) optical detection channels. In other embodiments, the self-aligning fiber optic system may include 4, 6, 8, 10, 12, 14, or 16 optical detection channels.

[0037] In some embodiments, the presently disclosed microfluidic systems, instruments, and cartridges, including self-aligning fiber optic systems and methods, provide an instrument fiber optic coupler on the microfluidic instrument side of a microfluidic system and a cartridge fiber optic connector on the microfluidic device (or cartridge) side of the microfluidic system, which engage and align in one or two stages: (1) a course alignment stage that aligns the instrument fiber optic coupler to the cartridge fiber optic connector, and / or (2) a fine alignment stage that individually aligns each optical channel of the instrument fiber optic coupler and the cartridge fiber optic connector.

[0038] In some embodiments, the presently disclosed microfluidic systems, devices, and cartridges, including the self-aligning fiber optic systems and methods, provide an instrument optical fiber coupler on the microfluidic device side of a microfluidic system that may include a line or arrangement of a plurality (e.g., 16) of instrument ferrule assemblies, each of which may include a commercially available ferrule. Generally, any number of instrument ferrule assemblies may be used. For example, in some embodiments, the microfluidic system may include a line or arrangement of about four (4) to about sixteen (16), about four (4) to about fourteen (14), about (6) to about twelve (12) instrument ferrule assemblies. In other embodiments, the microfluidic system may include 4, 6, 8, 10, 12, 14, or 16 instrument ferrule assemblies. Additionally, in some embodiments, each of the instrument ferrule assemblies includes an instrument optical fiber.

[0039] In some embodiments, the presently disclosed microfluidic systems, instruments, and cartridges, including the self-aligning optical fiber systems and methods, provide a cartridge optical fiber connector on the microfluidic device (or cartridge) side of a microfluidic system that may include a line or arrangement of a plurality (e.g., 16) of cartridge ferrule assemblies, each of which may include a cup-shaped custom ferrule designed to accept a commercially available ferrule of the instrument ferrule assembly and implement fine alignment of the optical fiber. Generally, any number of cartridge ferrule assemblies may be used. For example, in some embodiments, the microfluidic system may include a line or arrangement of about four (4) to about sixteen (16), about four (4) to about fourteen (14), about (6) to about twelve (12) cartridge ferrule assemblies. In still other embodiments, the microfluidic system may include 4, 6, 8, 10, 12, 14, or 16 cartridge ferrule assemblies. Additionally, in some embodiments, each of the cartridge ferrule assemblies includes a cartridge optical fiber.

[0040] In some embodiments, the presently disclosed microfluidic systems, instruments, and cartridges, including self-aligning fiber optic systems and methods, provide an instrument fiber optic coupler on the microfluidic instrument side of the microfluidic system and a cartridge fiber optic connector on the microfluidic device (or cartridge) side of the microfluidic system to simultaneously align a set of optical fibers (e.g., 16) in the cartridge fiber optic connector onto a like number of optical fibers (e.g., 16) in the instrument fiber optic coupler and simultaneously transmit optical results via established optical channels for diagnostics within the microfluidic system and / or instrument.

[0041] In some embodiments, the presently disclosed microfluidic systems, devices, and cartridges and methods can provide a self-aligning fiber optic system in which the tolerances for aligning multiple fiber optic lines over some distance are substantially entirely present in each individual mating of one instrument ferrule assembly to one cartridge ferrule assembly, rather than in a collective arrangement of, for example, 16 instrument ferrule assemblies mated to 16 cartridge ferrule assemblies over some distance (although other arrangements are contemplated herein). Although the presently disclosed self-aligning fiber optic system may be described herein with respect to microfluidic systems, devices, and cartridges, the presently disclosed self-aligning fiber optic system is not limited to only microfluidic applications. This is merely exemplary. The presently disclosed self-aligning fiber optic system may be used in any application requiring an optical coupling and / or interface between two systems, devices, and / or components.

[0042] Additionally, although the presently disclosed self-aligning fiber optic systems may be described herein with respect to supporting sixteen (16) optical detection channels in microfluidic systems, instruments, and cartridges, the presently disclosed self-aligning fiber optic systems are not limited to supporting only sixteen (16) optical detection channels. This is by way of example only. The presently disclosed self-aligning fiber optic systems may be provided to support any number of optical detection channels, as described elsewhere herein.

[0043] 1, there is shown a block diagram of a microfluidic system 100 including one embodiment of the presently disclosed self-aligning fiber optic system for optically coupling a microfluidic instrument to a microfluidic device (or cartridge). In this embodiment, the microfluidic system 100 may include a self-aligning fiber optic system 110. The self-aligning fiber optic system 110 further includes an instrument fiber optic coupler 112 on the instrument side of the microfluidic system 100 and a cartridge fiber optic connector 114 on the microfluidic cartridge side of the microfluidic system 100.

[0044] For example, microfluidic system 100 includes a microfluidic device 160 and a microfluidic cartridge 170, which may be optically coupled using self-aligning fiber optic system 110. In this embodiment, the device fiber optic coupler 112 of self-aligning fiber optic system 110 may be provided in microfluidic device 160. Additionally, the cartridge fiber optic connector 114 of self-aligning fiber optic system 110 may be provided in microfluidic cartridge 170.

[0045] The microfluidic device 160 may further include an optical detection system 162 and a movable slide mechanism 164. The instrument fiber optic coupler 112 in the microfluidic device 160 may include an arrangement of optical fibers 154, such as sixteen optical fibers 154. The sixteen optical fibers 154 may run from the instrument fiber optic coupler 112 to the optical detection system 162 via a fiber optic bundle 166.

[0046] The light detection system 162 of the microfluidic device 160 may be, for example, a light measurement system including an illumination source (not shown) and a light measurement device (not shown). For example, the light detection system 162 may be a fluorometer that provides both excitation and detection. In this example, the illumination source (e.g., a light source in the visible range (400-800 nm)) and the light measurement device (e.g., a charge-coupled device, a photodetector, a spectrometer, a photodiode array) may be disposed with respect to the microfluidic cartridge 170. Furthermore, the microfluidic system 100 is not limited to only one light detection system 162 (e.g., only one illumination source and one light measurement device). The microfluidic system 100 may include multiple light detection systems 162 (e.g., multiple illumination sources and / or multiple light measurement devices) to support multiple detection spots 178 of the microfluidic cartridge 170.

[0047] The movable slide mechanism 164 of the microfluidic device 160 can be any mechanism for sliding the microfluidic device 160 towards the fixed microfluidic cartridge 170 disposed in the same plane. The sliding action of the movable slide mechanism 164 is used to engage the device optical fiber coupler 112 in the microfluidic device 160 with the cartridge optical fiber connector 114 in the microfluidic cartridge 170. In this manner, optical coupling is created between the microfluidic device 160 and the microfluidic cartridge 170. That is, an optical path or channel is provided from the detection spot 178 of the microfluidic cartridge 170 to the optical detection system 162 of the microfluidic device 160. One embodiment of the movable slide mechanism 164 is shown in FIG. 2A.

[0048] Microfluidic cartridge 170 may be, for example, any disposable or non-disposable digital microfluidic (DMF) device (or cartridge), droplet actuator device (or cartridge), droplet manipulation device (or cartridge), etc. Cartridge fiber optic connector 114 may include an arrangement of optical fibers 146, such as 16 optical fibers 146. The 16 optical fibers 146 may run from cartridge fiber optic connector 114 to 16 respective sensors 176 and / or 16 respective detection spots 178 of microfluidic cartridge 170.

[0049] In one embodiment, the sensors 176 may be surface plasmon resonance (SPR) sensors supporting detection spots 178 (i.e., detection channels) on the microfluidic cartridge 170. In this embodiment, each SPR sensor 176 may be a functionalized SPR sensor 176 (i.e., a ligand immobilized on a surface).

[0050] In another embodiment, the sensors 176 may be localized surface plasmon resonance (LSPR) sensors. In this embodiment, each LSPR sensor 176 may be functionalized to (1) detect, for example, specific molecules (e.g., target analytes) and / or chemicals in a sample, and (2) analyze the analytes, i.e., measure binding events in real time and extract on-rate, off-rate, and / or affinity information.

[0051] In one embodiment, the detection spot 178 of the microfluidic cartridge 170 may be a specific droplet operation electrode (i.e., an electrowetting electrode, not shown) dedicated to optical detection operations of the microfluidic system 100. Further details of the sensor 176 and the detection spot 178 of the microfluidic cartridge 170 are shown and described below with reference to FIG.

[0052] In the self-aligning fiber optic system 110, the optical fibers 154 of the instrument fiber optic coupler 112 align and optically couple with the respective optical fibers 146 of the cartridge fiber optic connector 114. Further details of the optical coupling mechanism of the self-aligning fiber optic system 110 are shown and described below with reference to Figures 2A-26.

[0053] Additionally, the self-aligning fiber optic system 110 may not be limited to supporting only 16 optical detection channels, such as the 16 optical fibers 154 of the instrument fiber optic coupler 112 optically coupled to the 16 optical fibers 146 of the cartridge fiber optic connector 114. The self-aligning fiber optic system 110, including the instrument fiber optic coupler 112 and the cartridge fiber optic connector 114, may be designed to support any number of optical detection channels.

[0054] Referring now to FIG. 2A, this is a perspective view of an exemplary instantiation of a microfluidic system 100 shown in FIG. 1 and including a microfluidic device 160 optically coupled to a microfluidic cartridge 170 using the presently disclosed self-aligning optical fiber system 110.

[0055] In this embodiment, the movable slide mechanism 164 may include a slidable base plate 210 attached to a rail 212 and a back plate 214 attached to the end of the slidable base plate 210 furthest from the microfluidic cartridge 170. Additionally, the movable slide mechanism 164 may include a motor 216 that remains fixed relative to the slidable base plate 210 and the back plate 214. A lead screw 218 of the motor 216 may be threaded through a threaded hole in the back plate 214. In general, the motor 216 may be used to advance and / or retract the device fiber optic coupler 112 in the microfluidic device 160 relative to the cartridge fiber optic connector 114 in the microfluidic cartridge 170.

[0056] Additionally, the instrument fiber optic coupler 112 of the self-aligning fiber optic system 110 is disposed at the end of the slidable base plate 210 opposite the back plate 214. The instrument fiber optic coupler 112 may be held at the end of the slidable base plate 210 using a screw or fastener 220 and a spring 222 on each side of the slidable base plate 210 to engage each end of the instrument fiber optic coupler 112. In this arrangement, the screw or fastener 220 floats on the spring 222. The screw or fastener 220 is not used to pull and engage the instrument fiber optic coupler 112 to the movable slide mechanism 164. Rather, the screw or fastener 220 provides a slide guide, and the threading action of the motor 216 and lead screw 218 may be used to translate the slidable base plate 210 in the same plane as the microfluidic cartridge 170. In doing so, the entire movable slide mechanism 164 of the microfluidic device 160, the device fiber optic coupler 112, and the cartridge fiber optic connector 114 are pulled together and engaged.

[0057] FIG. 2A also shows that the instrument fiber optic coupler 112 may include a coupler housing 116 having dowel pins 118 on each side. In one embodiment, the dowel pins 118 may be 1.6 mm diameter dowel pins. Furthermore, the cartridge fiber optic connector 114 may include a connector housing 132 having cartridge datum holes 134. The two cartridge datum holes 134 in the connector housing 132 of the cartridge fiber optic connector 114 are designed to receive the two dowel pins 118 in the coupler housing 116 of the instrument fiber optic coupler 112. Furthermore, FIG. 2B shows a perspective view of one embodiment of the microfluidic device portion of the microfluidic system 100 shown in FIG. 1. For example, FIG. 2B shows further details of a cable 211 for providing the fiber optic bundle 166 to the instrument fiber optic coupler 112.

[0058] Further details of the alignment of the instrument fiber optic coupler 112 and the cartridge fiber optic connector 114 are shown and described below with reference to Figures 3-25.

[0059] In the microfluidic system 100, the instrument fiber optic coupler 112 of the microfluidic device 160 and the cartridge fiber optic connector 114 of the microfluidic device 160 may engage and align in two stages: (1) a course alignment stage in which the instrument fiber optic coupler 112 is aligned with the cartridge fiber optic connector 114, and (2) a fine alignment stage in which each optical channel of the instrument fiber optic coupler 112 and the cartridge fiber optic connector 114 is individually aligned. A process using a movable slide mechanism 164 may be used to perform the first of the two stages, which is the course alignment stage in which the dowel pins 118 are used to align the instrument fiber optic coupler 112 with the cartridge fiber optic connector 114. In this course alignment stage, the optical fibers 154 (not visible) of the instrument fiber optic coupler 112 may be aligned (end-to-end or face-to-face) to within about ±0.7 mm of the optical fibers 146 (not visible) of the cartridge fiber optic connector 114.

[0060] 3, 4, and 5, which are perspective views of one embodiment of the presently disclosed self-aligning fiber optic system 110 shown in FIGS. 1 and 2A and including an instrument fiber optic coupler 112 and a cartridge fiber optic connector 114. Additionally, FIGS. 3, 4, and 5 show the instrument fiber optic coupler 112 in relation to the cartridge fiber optic connector 114, but not yet mechanically and / or optically coupled. Additionally, FIGS. 3, 4, and 5 more clearly show the two dowel pins 118 in the coupler housing 116 of the instrument fiber optic coupler 112 in relation to the two cartridge datum holes 134 in the connector housing 132 of the cartridge fiber optic connector 114. Additionally, FIGS. 3 and 4 show fastener holes 122 in the ends of the coupler housing 116 (e.g., one on each end of the coupler housing 116) for receiving screws or fasteners 220 of the slidable base plate 210.

[0061] In this example, the coupler housing 116 of the instrument fiber optic coupler 112 may hold an arrangement of instrument ferrule assemblies 124 including optical fibers 154 (not visible). In this example, the coupler housing 116 holds sixteen instrument ferrule assemblies 124 arranged in a row for holding the optical fibers 154. Similarly, the connector housing 132 of the cartridge fiber optic connector 114 may hold an arrangement of cartridge ferrule assemblies 136 including optical fibers 146 (not visible). In this example, the connector housing 132 holds sixteen cartridge ferrule assemblies 136 for holding the optical fibers 146 arranged in a row.

[0062] Additionally, the microfluidic cartridge 170 may include a bottom substrate 172 and a top substrate 174 separated by a droplet operations gap (not shown). In one embodiment, the bottom substrate 172 may be a printed circuit board (PCB) and the top substrate 174 may be a substantially transparent glass or plastic substrate. Additionally, the connector housing 132 of the cartridge fiber optic connector 114 may be integrated into the top substrate 174 of the microfluidic cartridge 170. For example, the connector housing 132 and the top substrate 174 may be a one-piece molded plastic design. Additionally, the bottom substrate 172 may include any arrangement of droplet operations electrodes (i.e., electrowetting electrodes, not shown) for performing droplet operations on a droplet operations surface.

[0063]

[0033] Referring now to Figure 6, a perspective view shows further details of the presently disclosed self-aligning fiber optic system 110 shown in Figures 1-5. For example, Figure 6 shows only the arrangement of the instrument ferrule assembly 124 of the instrument fiber optic coupler 112. Further details of the instrument fiber optic coupler 112 and the instrument ferrule assembly 124 are shown and described below with reference to Figures 7A-14.

[0064] 6 further illustrates the microfluidic cartridge 170 lacking the top substrate 174, and shows further details of the cartridge ferrule assembly 136. For example, each cartridge ferrule assembly 136 may include a cartridge ferrule 138 that holds an optical fiber 146. The distal end 150 of the optical fiber 146 may include a sensor 176 (e.g., an SPR sensor 176 and / or an LSPR sensor 176). Furthermore, the distal end 150 of the optical fiber 146 with the sensor 176 may be positioned at a particular detection spot 178 that is a particular detection channel of the microfluidic cartridge 170. In another embodiment, the distal end 150 of the optical fiber 146 may lack the sensor 176, and instead, the sensor 176 may be provided at the detection spot 178 as part of the microfluidic cartridge 170 and / or droplet operations. Further details of the cartridge ferrule assembly 136 are shown and described below with reference to FIGS. 15A-19.

[0065] 7A and 7B, which are perspective and exploded views, respectively, of one embodiment of an instrument ferrule assembly 124 of the instrument fiber optic coupler 112 shown in Figures 13 and 14. In this embodiment, each instrument ferrule assembly 124 of the instrument fiber optic coupler 112 may include an instrument ferrule 152 having a tip 153, an optical fiber 154 encased in a cable cladding 155, a flat washer 156, and a spring 158.

[0066] In one embodiment, the instrument ferrule 152 may be a commercially available ferrule, such as a ferrule available from Precision Fiber Products, Inc. (PFP) (Chula Vista, Calif.) in the family of part numbers: MM-FER2007CF-XXXX. FIG. 8 shows various views of one embodiment of a PFP instrument ferrule 152 that may be used in the instrument ferrule assembly 124. In this embodiment, the instrument ferrule 152 may have an overall length of about 11.80 mm. The outer diameter (OD) of the tip 153 may be about 1.25 mm. The end face of the tip 153 may be conical. The bore diameter of the instrument ferrule 152 for receiving the optical fiber 154 may be, for example, about 80 μm to about 126 μm. Furthermore, in the instrument ferrule 152, the ferrule material may be, for example, ceramic zirconia (ZrO2) and the flange material may be, for example, nickel-plated brass.

[0067] In the instrument ferrule assembly 124, the OD of the optical fiber 154 may be, for example, about 100 μm to about 125 μm. The OD of the cable cladding 155 surrounding the optical fiber 154 may be, for example, about 0.125+0 / −0.008 mm.

[0068] In the instrument ferrule assembly 124, the flat washer 156 may be, for example, an M2 poly slider washer that is about 0.4 mm to about 0.5 mm thick with an OD of about 3.5 mm.

[0069] In the instrument ferrule assembly 124, the spring 158 may be a coiled wire type spring having a ground end.

[0070] In the instrument ferrule assembly 124, still referring to FIGS. 7A and 7B, a flat washer 156 may be placed against the back of the flange portion of the instrument ferrule 152. A spring 158 may then be placed against the back of the flat washer 156. An exposed portion of the optical fiber 154 may then be inserted into the instrument ferrule 152 and advanced to the tip 153 of the instrument ferrule 152. Some length of the cable cladding 155 may then engage inside the rear portion of the instrument ferrule 152. When the instrument ferrule assembly 124 is fully assembled, an end face of the optical fiber 154 may be exposed at an opening in front of the tip 153 of the instrument ferrule 152. Thus, the optical fiber 154 of the instrument ferrule assembly 124 may be optically coupled to a corresponding optical fiber 146 of a corresponding cartridge ferrule assembly 136. An example thereof is shown as follows with reference to FIGS. 20 and 21.

[0071] 9A and 9B, which are other perspective views of the instrument ferrule assembly 124 shown in FIG. 7A. Additionally, FIG. 10 shows a side view of the instrument ferrule assembly 124. Additionally, FIGS. 11A and 11B show front and rear views, respectively, of the instrument ferrule assembly 124. FIGS. 9A-11B show that the instrument ferrule assembly 124 may further include a shoulder washer 128 against a tip face of the flange portion of the instrument ferrule 152. That is, the shoulder washer 128 may be provided on the tip 153 of the instrument ferrule 152. The shoulder washer 128 may be, for example, an M2 shoulder countersunk washer.

[0072] 12, which is a perspective view of the instrument ferrule assembly 124 shown in FIG. 7A in various states of assembly. For example, the instrument ferrule assembly 124 is shown lacking the spring 158. The flat washer 156 is shown alone with respect to the optical fiber 154. The shoulder washer 128 is shown alone with respect to the optical fiber 154. The instrument ferrule 152 is shown alone with respect to the optical fiber 154. The spring 158 is shown alone with respect to the optical fiber 154. The optical fiber 154 is shown alone. The instrument ferrule assembly 124 is then shown fully assembled.

[0073] 13 and 14, which are perspective and exploded views, respectively, of one embodiment of an instrument fiber optic coupler 112 of the presently disclosed self-aligning fiber optic system 110 shown in FIGURES 1-6. FIGURES 13 and 14 illustrate that the instrument fiber optic coupler 112 may further include a coupler clamping plate 120 for holding a plurality of instrument ferrule assemblies 124 secured to the coupler housing 116. Additionally, the coupler clamping plate 120 may be secured to the coupler housing 116 via a plurality of screws 126.

[0074] 1-6 , is a perspective view of one embodiment of a cartridge ferrule assembly 136 of the cartridge fiber optic connector 114 of the presently disclosed self-aligning fiber optic system 110. In this embodiment, the cartridge ferrule assembly 136 may include a cartridge ferrule 138 and an optical fiber 146. The cartridge ferrule 138 may further include a receiving end 140 and a fiber holder end 142. The receiving end 140 of the cartridge ferrule 138 may be cup-shaped and sized to receive a tip 153 of an instrument ferrule 152 of the instrument ferrule assembly 124.

[0075] In the cartridge ferrule assembly 136, the OD of the optical fiber 146 may be, for example, about 200 μm to about 230 μm. The OD of the cable cladding (not shown) surrounding the optical fiber 146 may be, for example, about 0.23+0 / −0.008 mm.

[0076] The optical fiber 146 may have a proximal end 148 and a distal end 150. The proximal end 148 of the optical fiber 146 may be received in a fiber centering channel 144 in the receiving end 140 of the cartridge ferrule 138, as shown in Figure 15B, which is a cross-sectional view of the cartridge ferrule assembly 136 taken along line AA in Figure 15A. A length of the optical fiber 146 runs through the fiber holder end 142 of the cartridge ferrule 138, and a distal end 150 of the optical fiber 146 extends outwardly away from the fiber holder end 142.

[0077] Additionally, Figures 16A and 16B respectively show top and side views of the cartridge ferrule assembly 136. Additionally, Figures 17A and 17B respectively show front and rear views of the cartridge ferrule assembly 136. Additionally, Figure 18 shows an exploded view of the cartridge ferrule assembly 136.

[0078] 19, a cross-sectional view showing further details of one embodiment of the cartridge ferrule 138 of the cartridge ferrule assembly 136 shown in FIG. 15A. In this embodiment, the overall length of the cartridge ferrule 138 may be about 7.4 mm. The overall diameter of the receiving end 140 of the cartridge ferrule 138 may be about 3.1 mm. The ID (inner diameter) of the receiving end 140 of the cartridge ferrule 138 may be about 1.25 mm. The overall cross-section of the fiber holder end 142 of the cartridge ferrule 138 may be about 1.6 mm. The ID of the fiber holder end 142 of the cartridge ferrule 138 may be about 2 mm. The ID of the fiber centering channel 144 leading to the receiving end 140 of the cartridge ferrule 138 may be about 0.23 mm.

[0079] Additionally, a lead-in bevel or chamfer may be provided at the openings of both the receiving end 140 and the fiber holder end 142 of the cartridge ferrule 138. The lead-in bevel or chamfer may be used to provide an extra lead-in, for example, about 0.8 mm to about 0.9 mm, during mating between the tip 153 of the instrument ferrule 152 and the receiving end 140 of the cartridge ferrule 138 during alignment.

[0080] The fiber centering channel 144 is designed to hold a proximal end 148 of an optical fiber 146. When the instrument ferrule assembly 124 is fully assembled, an end face of the optical fiber 146 may be exposed at the bottom opening of the receiving end 140 of the cartridge ferrule 138. Thus, the optical fiber 146 of the cartridge ferrule assembly 136 may be optically coupled to a corresponding optical fiber 154 of the corresponding instrument ferrule assembly 124. That is, the optical fiber 146 of the cartridge ferrule assembly 136 and the optical fiber 154 of the instrument ferrule assembly 124 may face each other or be end-to-end inside the cup-shaped receiving end 140 of the cartridge ferrule 138. One embodiment thereof is shown as follows with reference to FIGS. 20 and 21.

[0081] 20 and 21, which are cross-sectional views of a portion of the presently disclosed self-aligning fiber optic system 110 shown in FIGS. 1-6 and showing the instrument fiber optic coupler 112 and the cartridge fiber optic connector 114 fully engaged together.

[0082] In the self-aligning fiber optic system 110, the OD of the optical fiber 146 of the cartridge ferrule assembly 136 may be larger than the OD of the optical fiber 154 of the instrument ferrule assembly 124. For example, the OD of the optical fiber 146 may be about 200 μm to about 230 μm, and the OD of the optical fiber 154 may be about 100 μm to about 125 μm. This allows for a certain tolerance that the end of the optical fiber 154 of the instrument ferrule assembly 124 aligns and matches with the end of the optical fiber 146 of the cartridge ferrule assembly 136. In the self-aligning fiber optic system 110, this configuration for the optical fibers 146 and 154 provides an alignment tolerance of better than about ±50 μm.

[0083] Again, in the microfluidic system 100, the instrument fiber optic coupler 112 of the microfluidic device 160 and the cartridge fiber optic connector 114 of the microfluidic device 160 may engage and align in two stages: (1) a course alignment stage that aligns the instrument fiber optic coupler 112 to the cartridge fiber optic connector 114, and (2) a fine alignment stage that individually aligns each optical channel of the instrument fiber optic coupler 112 and the cartridge fiber optic connector 114. As previously mentioned, the dowel pins 118 of the align instrument fiber optic coupler 112 may be used to perform the course alignment stage of the instrument fiber optic coupler 112 to the cartridge fiber optic connector 114, which is the first of the two stages.

[0084] 20 and 21, the process of engaging the tip 153 carrying the optical fiber 154 of the instrument ferrule 152 of the instrument ferrule assembly 124 with the receiving end 140 of the cartridge ferrule 138 of the cartridge ferrule assembly 136 may be used to perform the second of two stages, a fine alignment stage of the instrument fiber optic coupler 112 to the cartridge fiber optic connector 114. In this fine alignment stage, the optical fiber 154 of the instrument fiber optic coupler 112 may be aligned (end-to-end or face-to-face) to within about ±50 μm of the optical fiber 146 of the cartridge fiber optic connector 114.

[0085] 20 and 21 show the Z-alignment and coupling region 180. Additionally, alignment of the optical fibers 154 of the instrument fiber optic coupler 112 to the optical fibers 146 of the cartridge fiber optic connector 114 in the Z-alignment and coupling region 180 forms an optical channel 182 of the microfluidic system 100. Additionally, the spring-loaded compression of the springs 158 of the instrument ferrule assembly 124 of the instrument fiber optic coupler 112 allows the instrument ferrule 152 and the cartridge ferrule 138 to overlap in the Z-direction, allowing the fiber ends to mate against each other without leaving a substantial gap between them.

[0086] Additionally, the cartridge ferrule 138 may be clamped down using a plate with a screw stop, and the instrument ferrule 152 may be allowed to float by leaving a gap 184 between the coupler clamp plate 120 and the instrument ferrule 152. The coupler clamp plate 120 allows attachment of the instrument ferrule 152, prevents the instrument ferrule 152 from falling off during shipping, and limits float play. The floating instrument ferrule 152 creates a compliance system that allows for individual self-aligning ferrules between the microfluidic cartridge 170 and the microfluidic device 160.

[0087] In some embodiments, optical gel may be applied onto the ferrule interface between the ends of the two mating optical fibers 146 and 154. This, combined with the z-direction overlap with the spring-loaded compression of the spring 158, may be used to ensure the quality of the optical transmission. A recessed ring (not shown) and vent holes around the mating face of the cartridge ferrule 138 may allow the optical gel and trapped air to escape during the mating operation.

[0088] 22 and 23, which are top views of the equipment fiber optic coupler 112 for the cartridge fiber optic connector 114 of the presently disclosed self-aligning fiber optic system 110 shown in Figures 1-6. Additionally, Figures 24 and 25 are bottom views of the equipment fiber optic coupler 112 for the cartridge fiber optic connector 114 of the presently disclosed self-aligning fiber optic system 110.

[0089] 26, there is shown a flow diagram of one embodiment of a method 300 of use of the presently disclosed microfluidic system 100 including the self-aligning fiber optic system 110 shown in FIGS. 1-25. The method 300 may include, but is not limited to, the following steps:

[0090] At step 310, a microfluidic system, microfluidic device, and / or microfluidic cartridge including the presently disclosed self-aligning optical fiber system is provided. For example, a microfluidic system 100 including a microfluidic device 160, a microfluidic cartridge 170, and including the presently disclosed self-aligning optical fiber system 110 as shown and described above with reference to Figures 1-25 may be provided.

[0091] In step 315, an instrument fiber optic coupler in the microfluidic device is provided with respect to a cartridge fiber optic connector in the microfluidic cartridge. For example, in the self-aligning fiber optic system 110, an instrument fiber optic coupler 112 in the microfluidic device 160 is provided with respect to a cartridge fiber optic connector 114 in the microfluidic cartridge 170.

[0092] In step 320, a first, or course optical alignment step of the instrument fiber optic coupler in the microfluidic device to the cartridge fiber optic connector in the microfluidic cartridge is performed. For example, a fine optical alignment step of the instrument fiber optic coupler 112 in the microfluidic device 160 to the cartridge fiber optic connector 114 in the microfluidic cartridge 170 is performed. For example, the movable slide mechanism 164 of the microfluidic device 160 may be used to translate the instrument fiber optic coupler 112 towards the fixed cartridge fiber optic connector 114 in the microfluidic cartridge 170. In doing so, the course alignment step uses the dowel pins 118 for initial engagement and alignment of the instrument fiber optic coupler 112 to the cartridge fiber optic connector 114. In this course alignment step, the optical fibers 154 of the instrument fiber optic coupler 112 may be aligned (end-to-end or face-to-face) to within about ±0.7 mm of the optical fibers 146 of the cartridge fiber optic connector 114.

[0093] In step 325, a second or fine optical alignment step of the instrument optical fiber coupler in the microfluidic device to the cartridge optical fiber connector in the microfluidic cartridge is performed. For example, the movable slide mechanism 164 of the microfluidic device 160 may be used to continue translating the instrument optical fiber coupler 112 toward the fixed cartridge optical fiber connector 114 in the microfluidic cartridge 170. In doing so, the fine optical alignment step may be accomplished by fully engaging the instrument ferrule 152 (with optical fiber 154) of the instrument ferrule assembly 124 with the cartridge ferrule 138 (with optical fiber 146) of the cartridge ferrule assembly 136. In this fine alignment step, the optical fiber 154 of the instrument optical fiber coupler 112 may be aligned (end-to-end or face-to-face) to within about ±50 μm of the optical fiber 146 of the cartridge optical fiber connector 114.

[0094] In step 330, optical detection operations of the microfluidic system, microfluidic device, and / or microfluidic cartridge are performed using the presently disclosed self-aligning optical fiber system. For example, optical detection operations of the microfluidic system 100, microfluidic device 160, and / or microfluidic cartridge 170 may be performed using the presently disclosed self-aligning optical fiber system 110. For example, the microfluidic cartridge 170 may be used to perform DMF operations (or droplet operations) for processing biological materials. In these processes, optical detection operations may occur, with the self-aligning optical fiber system 110 providing an optical path or channel from a detection spot 178 of the microfluidic cartridge 170 to an optical detection system 162 of the microfluidic device 160.

[0095] 1-26, the presently disclosed microfluidic system 100, microfluidic device 160, microfluidic cartridge 170, and method 300 can provide a self-aligning optical fiber system 110 that can include an instrument optical fiber coupler 112 on the microfluidic device side of the microfluidic system 100 and a cartridge optical fiber connector 114 on the microfluidic cartridge side of the microfluidic system 100.

[0096] 1-26, the presently disclosed microfluidic system 100, microfluidic device 160, microfluidic cartridge 170, and method 300 can provide a self-aligning optical fiber system 110 that ensures a good optical fit (spacing of less than about 10 um, concentricity tolerance of less than about 100 um) between the device optical fiber coupler 112 on the microfluidic device side of the microfluidic system 100 and the cartridge optical fiber connector 114 on the microfluidic cartridge side of the microfluidic system 100.

[0097] 1-26, the presently disclosed microfluidic system 100, microfluidic device 160, microfluidic cartridge 170, and method 300 can provide a self-aligning optical fiber system 110 in which the device optical fiber coupler 112 on the microfluidic device side of the microfluidic system 100 and the cartridge optical fiber connector 114 on the microfluidic cartridge side of the microfluidic system 100 can support any number of optical detection channels, such as, but not limited to, sixteen (16) optical detection channels.

[0098] Referring again to Figures 1-26, the presently disclosed microfluidic system 100, microfluidic device 160, microfluidic cartridge 170, and method 300 can provide a self-aligning optical fiber system 110 in which an instrument optical fiber coupler 112 on the microfluidic device side of the microfluidic system 100 and a cartridge optical fiber connector 114 on the microfluidic cartridge side of the microfluidic system 100 engage and align in two stages: (1) a course alignment stage in which the instrument optical fiber coupler 112 is aligning with the cartridge optical fiber connector 114, and (2) a fine alignment stage in which each optical channel of the instrument optical fiber coupler 112 and the cartridge optical fiber connector 114 is individually aligned.

[0099] 1-26, the presently disclosed microfluidic system 100, microfluidic device 160, microfluidic cartridge 170, and method 300 can provide a self-aligning optical fiber system 110 in which the instrument fiber optic coupler 112 on the microfluidic device side of the microfluidic system 100 and the cartridge optical fiber connector 114 on the microfluidic cartridge side of the microfluidic system 100 can include a line or arrangement of multiple (e.g., 16) instrument ferrule assemblies 124, each of which can include a commercially available ferrule.

[0100] 1-26, the presently disclosed microfluidic system 100, microfluidic device 160, microfluidic cartridge 170, and method 300 can provide a self-aligning optical fiber system in which the device optical fiber coupler 112 on the microfluidic device side of the microfluidic system 100 and the cartridge optical fiber connector 114 on the microfluidic cartridge side of the microfluidic system 100 can include a line or arrangement of multiple (e.g., 16) cartridge ferrule assemblies 136, each of which can include a cup-shaped custom cartridge ferrule 138 designed to accept a commercially available ferrule of the device ferrule assembly 124 and implement fine alignment of the optical fiber.

[0101] 1-26, the presently disclosed microfluidic system 100, microfluidic device 160, microfluidic cartridge 170, and method 300 can provide a self-aligning optical fiber system 110 in which the tolerances for aligning multiple optical fiber lines over some distance are substantially entirely present in each individual mating of one instrument ferrule assembly 124 to one cartridge ferrule assembly 136, rather than in the collective arrangement of, for example, sixteen instrument ferrule assemblies 124 mating to sixteen cartridge ferrule assemblies 136 over some distance.

[0102] 1-26, the presently disclosed microfluidic system 100, microfluidic device 160, microfluidic cartridge 170, and method 300 can provide a self-aligning optical fiber system 110 in which an instrument optical fiber coupler 112 on the microfluidic device side of the microfluidic system 100 and a cartridge optical fiber connector 114 on the microfluidic cartridge side of the microfluidic system 100 can simultaneously align a set of optical fibers (e.g., 16) in the cartridge optical fiber connector 114 onto a like number of optical fibers (e.g., 16) in the instrument ferrule assembly 124, which can be used to simultaneously transmit optical results via established optical channels for diagnostics in the microfluidic system 100 and / or the microfluidic device 160.

[0103] 1-26, the presently disclosed microfluidic system 100 and method 300 including the self-aligning optical fiber system 110 can provide a simple and cost-effective way to automate the alignment of multiple fibers in the microfluidic cartridge 170 and microfluidic device 160 and establish various channels for optical transmission. This innovation places only a single low-cost injection molded polymer part on the disposable cartridge side and retains all the mechanics on the device side.

[0104] 1-26, the presently disclosed microfluidic system 100 including self-aligning fiber optic system 110 and method 300 can provide a mechanism whereby each individual cartridge ferrule assembly 136 of a microfluidic cartridge 170 can be independently processed prior to cartridge integration without affecting the mechanism alignment. This is possible because each fiber optic channel can be individually aligned and therefore part-to-part variations can not affect it. Independent processing is advantageous because it allows new chemistries to be applied to each individual sensor 176 of its corresponding cartridge ferrule assembly 136.

[0105] Following long-standing patent law convention, the terms "a," "an," and "the" refer to "one or more" when used in this application, including the claims. Thus, for example, a reference to "an object" includes a plurality of objects unless the context clearly indicates to the contrary (e.g., a plurality of objects), etc.

[0106] The terms "comprise," "comprises," "comprising," "include," "includes," and "including" are intended to be open-ended, and the recitation of items in a list is not the exclusion of other similar items that may be substituted for or added to the listed items.

[0107] Terms such as "preferably," "commonly," and "typically" are not used herein to limit the scope of the claimed embodiments or to imply that particular features are essential or required to the structure or function of the claimed embodiments. These terms are intended to highlight alternative or additional features that may or may not be utilized in a particular embodiment of the present disclosure.

[0108] The term "substantially" is utilized herein to represent the inherent degree of uncertainty that may result from any quantitative comparison, value, measurement, or other representation, and to represent the degree to which a quantitative representation may vary from the stated recitation without resulting in a change in the basic functionality of the subject matter at hand.

[0109] Various modifications and variations of the disclosed methods, compositions, and uses of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been disclosed in connection with specific preferred aspects or embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific aspects or embodiments.

[0110] For purposes of this specification and the appended claims, unless otherwise specified, all numbers expressing amounts, sizes, dimensions, proportions, shapes, formulations, parameters, percentages, quantities, properties, and other numerical values ​​used in the specification and claims are to be understood as being modified in all instances by the term "about," even if the term "about" does not explicitly appear with a value, amount, or range. Thus, unless specified to the contrary, the numerical parameters set forth in the following specification and the appended claims are not and need not be precise, but may be approximate and / or larger or smaller, as desired, to reflect tolerances, conversion factors, rounding off, measurement errors and the like, as well as other factors known to those of ordinary skill in the art depending upon the desired properties sought to be obtained by the presently disclosed subject matter. For example, the term "about" when referring to a value can be meant to encompass, in some embodiments, ±100%, in some embodiments, ±50%, in some embodiments, ±20%, in some embodiments, ±10%, in some embodiments, ±5%, in some embodiments, ±1%, in some embodiments, ±0.5%, and in some embodiments, ±0.1% variation from the particular amount, as variation is appropriate for performing the disclosed methods or employing the disclosed compositions.

[0111] Furthermore, the term "about," when used in connection with one or more numbers or numerical ranges, should be understood to refer to all such numbers, including every number in the range, and to modify that range by extending the boundaries above and below the numerical values ​​set forth. The recitation of numerical ranges by endpoints includes all numbers subsumed within that range, for example, integers including fractions thereof (e.g., recitation of 1-5 includes 1, 2, 3, 4, and 5, as well as fractions thereof, e.g., 1.5, 2.25, 3.75, 4.1, etc.), and any range within that range.

[0112] Although the foregoing subject matter has been described in some detail by way of examples and embodiments, for purposes of clarity of understanding, it will be understood by those skilled in the art that certain changes and modifications may be practiced within the scope of the appended claims.

[0113] Although the foregoing subject matter has been described in some detail by way of examples and embodiments, for purposes of clarity of understanding, it will be understood by those skilled in the art that certain changes and modifications may be practiced within the scope of the appended claims.

Claims

Claim 1 (a) A microfluidic device, including an optical detection system, said microfluidic device, and (b) a microfluidic cartridge, and (c) a self-aligning optical fiber system comprising said self-aligning optical fiber system optically couples said microfluidic device and said microfluidic cartridge, a microfluidic system. Claim 2 The self-aligning optical fiber system includes a device optical fiber coupler and a cartridge optical fiber connector, the microfluidic system according to claim 1. Claim 3 The optical detection system includes an illumination source and a light measurement device, the microfluidic system according to claim 1. Claim 4 The self-aligning optical fiber system includes a plurality of optical detection channels, each of said plurality of optical detection channels includes a device optical channel and a cartridge optical channel, the microfluidic system according to claim 1. Claim 5 Each of said device optical channels optically connects each of said cartridge optical channels to a light measurement device, the microfluidic system according to claim 4. Claim 6 The self-aligning optical fiber system includes about 4 - about 16 optical detection channels, the microfluidic system according to claim 4. Claim 7 The device optical fiber coupler includes a plurality of device ferrule assemblies each including a tip and a device optical fiber, the microfluidic system according to claim 2. Claim 8 The cartridge optical fiber connector further includes a receiving end that can receive each device ferrule assembly, and a plurality of cartridge ferrule assemblies each including a cartridge optical fiber, the microfluidic system according to claim 2. Claim 9 The microfluidic device further includes a movable slide mechanism, said movable slide mechanism is operable to generate an optical coupling between said microfluidic device and said microfluidic cartridge by engaging a device optical fiber coupler with a cartridge optical fiber connector, the microfluidic system according to claim 2. Claim 10 The movable slide mechanism is operable to engage a device ferrule assembly with a cartridge ferrule assembly, thereby coupling a device optical fiber to a cartridge optical fiber, the microfluidic system according to claim 9. Claim 11 The movable slide mechanism includes a slidable base plate attached to the rail, a back plate attached to an end of the slidable base plate, and a lead screw and an associated motor operable to advance and / or retract the device optical fiber coupler with respect to the cartridge optical fiber connector. The microfluidic system according to claim 9.

12. The microfluidic cartridge (a) a bottom substrate including a droplet operation surface, the bottom substrate, (b) an upper substrate further includes, The bottom substrate and the upper substrate are separated by a droplet operation gap therebetween. The microfluidic system according to claim 1.

13. The bottom substrate and / or the upper substrate includes a PCB substrate, a glass substrate, or a silicon substrate, and the PCB substrate, the glass substrate, or the silicon substrate is optionally coated with a dielectric layer and one or more electrodes operable for droplet operation. The microfluidic system according to claim 12.

14. The droplet operation gap between the bottom substrate and the upper substrate is filled with a filler fluid. The microfluidic system according to claim 12.

15. The filler fluid is a low-viscosity oil or a halogenated oil. The microfluidic system according to claim 14.

16. The microfluidic cartridge is a digital microfluidic cartridge (DMF). The microfluidic system according to claim 1.

17. The optical detection system includes one or more surface plasmon resonance (SPR) sensors, or one or more localized surface plasmon resonance (LSPR) sensors. The microfluidic system according to any one of claims 3 to 16.

18. A method for performing an optical detection operation, (a) providing a microfluidic system, the microfluidic system including a microfluidic device, a microfluidic cartridge, and a plurality of optical detection channels, (i) the microfluidic device includes a device optical fiber coupler, (ii) the microfluidic cartridge includes a cartridge optical fiber connector, the providing, (b) performing a first optical alignment step of aligning the device optical fiber coupler with the cartridge optical fiber connector (c) performing a second optical alignment step of individually aligning each of the optical detection channels; (d) performing an optical detection operation using the microfluidic system, the microfluidic device, and the microfluidic cartridge A method comprising:

19. The method according to claim 18, wherein the microfluidic device further includes a movable slide mechanism, and the first optical alignment step is performed by moving the movable slide mechanism until the optical fiber coupler engages with the optical fiber connector.

20. The method according to claim 19, wherein the optical fiber coupler is moved toward a fixed optical fiber connector.

21. The method according to claim 18, wherein the first optical alignment step provides a coarse alignment of each of the plurality of optical detection channels.

22. The second alignment step is performed by continuously translating the movable slide mechanism toward the microfluidic cartridge until the optical fiber coupler is fully engaged with the optical fiber connector, thereby individually aligning each of the optical detection channels. The method according to claim 19.

23. The method according to claim 22, wherein the second optical alignment step provides a fine alignment of each of the plurality of optical detection channels.

24. The optical fiber coupler further includes a plurality of device ferrule assemblies each including a tip and a device optical fiber, the optical fiber connector includes a receiving end capable of receiving each of the device ferrule assemblies, and further includes a plurality of cartridge ferrule assemblies each including a cartridge optical fiber. The movable slide is moved until each of the device ferrule assemblies engages with each of the cartridge ferrule assemblies, thereby connecting the device optical fiber to the cartridge optical fiber and generating the plurality of optical detection channels. The method according to claim 19.

25. The optical fiber coupler of the apparatus further includes a housing having one or more dowel pins, the cartridge optical connector further includes a housing having one or more datum holes, and the one or more datum holes receive the one or more dowel pins during the first alignment step, the method according to claim 19.

26. The method according to claim 25, wherein the dowel pin aligns the optical fiber coupler of the apparatus with the cartridge optical fiber connector.

27. The method according to claim 25, wherein the optical fiber of the apparatus is aligned within about ±0.7 mm of the cartridge optical fiber.

28. The second alignment step provides a z-direction alignment between the optical fiber coupler and the optical fiber connector, the method according to claim 19.

29. The second alignment step provides an alignment in direction between each of the device ferrule assemblies and each of the cartridge ferrule assemblies, and aligns the device optical fiber and the cartridge optical fiber facing each other with substantially no gap therebetween, the method according to claim 24.

30. The method according to claim 29, wherein the device ferrule assembly further includes a spring, and the spring aligns the device optical fiber and the cartridge optical fiber facing each other with substantially no gap therebetween.

31. The method according to claim 29, wherein the optical fiber of the apparatus is aligned within about ±50 μm of the cartridge optical fiber.

32. The method according to claim 24, wherein an optical gel is applied between the device optical fiber and the cartridge optical fiber.

33. The method according to claim 18, wherein the microfluidic system further includes an optical detection system including an illumination source and an optical measurement device.

34. The optical detection system includes surface plasmon resonance (SPR) or localized surface plasmon resonance (LSPR), and the optical detection system includes an SPR or LSPR illumination source and one or more SPR or LSPR optical measurement devices, the method according to claim 33.

35. The method according to any one of claims 18 to 34, wherein the microfluidic cartridge is a digital microfluidic cartridge (DMF).

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