Microfluidic chips and electrical interfaces for microchip electrophoresis
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-03-10
- Publication Date
- 2026-03-16
AI Technical Summary
Current microchip electrophoresis interfaces are insufficient for various applications, as they often lack long separation channels, achieve lower resolution, and have limitations in isolation voltage and throughput.
The development of a microfluidic chip with multiple sample wells and a corresponding electrical interface that includes a shared power amplifier, independent power amplifiers, and a selector to output power signals to electrodes, allowing for improved resolution, higher isolation voltage, and increased throughput.
The proposed solution enables longer separation channels, higher resolution, higher isolation voltage, and increased throughput in microchip electrophoresis, addressing the limitations of current interfaces.
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Abstract
Description
[Technical field]
[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Patent Application No. 17 / 701,594, filed March 22, 2022, the entire contents of which of the above-identified applications are incorporated by reference as if set forth herein. [Background technology]
[0002] Microfluidic devices and systems are becoming increasingly accepted and important as analytical tools in research and development laboratories in both academia and industry. This has fueled rapid advances in this technology over the past few years. One particular area of focus and research in microfluidic devices and systems involves microchip electrophoresis.
[0003] Generally speaking, electrophoresis utilizes differences in the migration rates of charged species (e.g., particles, molecules) through a separation medium under the influence of an electric field. In this way, species can be separated and / or characterized according to physical properties, most typically size. In electrophoresis, a sample containing the species of interest is placed at one end of a separation channel and a voltage difference is applied across both channel ends until a desired migration endpoint is reached. The separated analyte molecules may then be detected by various means (e.g., optical detection, x-radiography, or band extraction).
[0004] Microchip electrophoresis offers several advantages over other forms of electrophoresis, such as capillary electrophoresis. Among these advantages are that it can result in relatively fast analysis and relatively low consumption of both sample and reagents. FIG. 1A illustrates an example of a microchip electrophoresis configuration 11. The microchip electrophoresis configuration 11 can include a sample packing microchannel 12 intersecting a separation microchannel 14. Each of the microchannels 12, 14 can be filled with an ion-containing buffer, and a sample can be received in a sample inlet 13. The sample is forced (e.g., electrophoretically forced or vacuum forced) into the sample packing microchannel 12. Secondly, an electric field can be applied to the separation microchannel 14, and a plug of sample (usually consisting of only a few nanoliters, or even picoliter level) is moved or dispensed from the sample packing microchannel 12 into the separation microchannel 14. The plug of sample may be moved along the separation microchannel 14 and separated into small bands spanning detection points 18 for recording and analysis.
[0005] 1B shows a top-view schematic of another microchip electrophoresis configuration. Microchip 20 may include a sample packing microchannel 22 (between inlet 23 and well 1), a separation microchannel 24 (between well 7 and well 10), and a cross-injection microchannel 26 (between well 3 and well 8) that intersects both sample packing microchannel 22 and separation microchannel 24. Sample packing microchannel 22 may be coupled to a sipper (not shown in FIG. 1B) that extends vertically below the major surface of microchip 20 and is located at or near inlet 23. The sipper can draw sample from a well plate (not shown in FIG. 1B) either vacuum or electrophoretically. As the sample traverses the sample packing microchannel 22 from the inlet 23 to the sample waste well (i.e., well 1), a cross-injection voltage is applied to the cross-injection channel 26 via electrodes coupled to wells 3, 8 (not shown in FIG. 1B ) to move the plug of sample from the sample packing microchannel 22 into alignment with the separation microchannel 24. A separation voltage is then applied via electrodes coupled to wells 7, 10 to perform electrophoresis in the separation microchannel 24. The plug of sample may be moved along the separation microchannel 24 and separated into small bands that cross the detection point 28 for recording and analysis. In some circumstances, the sample may be combined with a stain or marker (e.g., from a channel coupled to well 4) after being drawn into the microchip 20. In some circumstances, the sample plug in the separation microchannel 24 may be destained to remove a portion of the stain.
[0006] 1C shows another example of a microchip electrophoresis arrangement 30 in which electrodes 32 are in contact with conductive contact elements 34 in wells 35 of a chip 36. The chip 36 comprises a first glass substrate 37, a second glass substrate 38 bonded to the first glass substrate 37, and a carrier element 39 bonded to the second glass substrate 38. The conductive contact elements 34 extend only partially into the carrier element 39. The first glass substrate 37 is provided with a number of channels 40, and the second substrate 38 is provided with a number of through holes 41. An electric potential can be applied to the fluid in the wells 35 via the electrodes 32 and the contact elements 34, thereby generating an electric field in the channels 40 as well and transporting charged components of the fluid through the channels 40. Summary of the Invention
[0007] Some aspects of the present disclosure provide an electrophoresis device. For example, an electrophoresis device according to the present disclosure may include a plurality of electrodes each including a galvanic contact configured to contact a respective contact of a microfluidic chip, a shared power amplifier configured to output a selected first power signal, and a selector configured to receive the first power signal from the shared power amplifier and to output the received power signal to a selected one or more of the plurality of electrodes.
[0008] In some embodiments, the plurality of electrodes is a plurality of first electrodes, and the electrophoresis device can include at least one independent power amplifier configured to output a selected second power signal to at least one second electrode separate from the plurality of first electrodes.
[0009] In some embodiments, the shared power amplifier may be configured to output a selected one of a constant current power signal, a constant voltage power signal, or a pulsed power signal as the first power signal. In some embodiments, the plurality of electrodes may include a plurality of sample electrodes and a plurality of ladder electrodes, and the selector may include a number of outputs corresponding to the sum of the number of the plurality of sample electrodes and the number of the plurality of ladder electrodes.
[0010] In some embodiments, the electrodes may be arranged in a format corresponding to a Society for Biomolecular Screening (SBS) plate format, for example, a 96-well plate format or a 384-well plate format.
[0011] In some embodiments, the plurality of electrodes may include between 5 and 500 electrodes, such as between 6 and 300 electrodes, for example, 126 electrodes.
[0012] In some embodiments, the electrophoresis device may include an electromechanical assembly configured to move a plurality of electrodes into contact with respective contacts of the microfluidic chip.
[0013] In some embodiments, the electrodes are encapsulated within an insulator block that galvanically isolates the electrodes.
[0014] In some embodiments, the contacts of the microfluidic chip may include conductive eyelets, and the electrodes may be configured to contact at least a portion of each conductive eyelet.
[0015] In some embodiments, the contacts may be pogo pins, sliding contacts, wires, and / or probes.
[0016] Another example of an electrophoresis device according to the present disclosure includes a plurality of first electrodes each including a galvanic contact surface configured to contact a respective contact surface of a microfluidic chip; at least one second electrode separate from the plurality of first electrodes and including a galvanic contact surface configured to contact a respective contact surface of the microfluidic chip; a first power amplifier configured to output a selected one of a constant current power signal, a constant voltage power signal, or a pulsed power signal as the first power signal; a selector configured to receive the first power signal from the first power amplifier and configured to select at least one of the plurality of first electrodes and output the received first power signal thereto; and a second power amplifier configured to output the selected one of the constant current power signal, the constant voltage power signal, or the pulsed power signal, different from the output of the first power amplifier, as a second power signal to the at least one second electrode.
[0017] Another example of an electrophoresis device according to the present disclosure includes a plurality of electrodes arranged corresponding to a Society for Biomolecular Screening (SBS) plate format, each including a galvanic contact surface configured to contact a respective contact surface of a microfluidic chip having sample wells arranged in the SBS plate format, first and second power amplifiers each configured to output different ones of a constant current power signal, a constant voltage power signal, or a pulsed power signal, and a selector configured to receive a power signal from the first power amplifier and configured to select at least one of the plurality of electrodes and output the received power signal thereto.
[0018] Some aspects of the present disclosure can provide a microfluidic chip. For example, a microfluidic chip according to the present disclosure can include a non-conductive substrate having a microfluidic channel therein, and a plurality of sample wells each having a galvanic contact fluidically coupled to the microfluidic channel and having a first portion on a top surface of the sample well and a second portion extending into the non-conductive substrate.
[0019] In some embodiments, the top surface of each sample well can include an annular eyelet. For example, the first portion of the galvanic contact can include the entire portion of the annular eyelet. The second portion of the galvanic contact that extends into the non-conductive substrate can be a portion of an annulus.
[0020] In some embodiments, the sample wells of the microfluidic chip may be arranged in a format, such as a 96-well or 384-well plate format, that corresponds to the Society for Biomolecular Screening (SBS) plate format.
[0021] In some embodiments, each sample well of the microfluidic chip may be in a non-conductive caddy. The non-conductive caddy may comprise an injection molded plastic material. The non-conductive caddy may comprise acrylic, polyphenylene ether (PPE), polycarbonate, or acrylonitrile butadiene styrene (ABS).
[0022] In some embodiments, the non-conductive substrate of the microfluidic chip can include cyclic olefin copolymer (COC), cyclic olefin polymer (COP), quartz, or soda-lime glass.
[0023] In some embodiments, the galvanic contacts of each sample well can include an electrically conductive carbon-based material.
[0024] In some embodiments, each sample well is configured to receive a respective electrode from an electrophoresis device, such as the electrophoresis devices discussed above.
[0025] In some embodiments, the microfluidics chip can include at least one reference well.
[0026] In some embodiments, the microfluidics chip includes a carrier that surrounds and insulates the sample wells, for example, the top surface of the sample wells may be flush with the top surface of the carrier.
[0027] Another example of a microfluidic chip according to the present disclosure can include a non-conductive substrate having a microfluidics channel therein, and a non-conductive caddy including a plurality of wells each providing a microfluidic connection with the microfluidics channel, each well having an upper conductive contact portion on its upper surface, each well having a conductive lower portion extending below the upper surface of the non-conductive substrate.
[0028] Another example of a microfluidic chip according to the present disclosure can include a non-conductive substrate having a microfluidic channel and a plurality of sample wells arranged corresponding to a Society for Biomolecular Screening (SBS) plate format, at least a portion of the plurality of sample wells being commonly connected to the microfluidic channel. Each sample well can have a galvanic contact including a first portion on a top surface of the sample well and a second portion extending into the non-conductive substrate.
[0029] Some aspects of the present disclosure provide a microfluidic system. For example, the microfluidic system according to the present disclosure may include a microfluidic chip having a plurality of sample wells with respective galvanic contacts on a top surface thereof, a plurality of first electrodes each configured to contact a respective one of the galvanic contacts of the microfluidic chip, first and second power amplifiers each configured to output respective different first and second power signals, a selector configured to receive the first power signal from the first power amplifier and to output the received first power signal to at least one selected one of the plurality of first electrodes, and at least one second electrode separate from the plurality of first electrodes and configured to receive the second power signal from the second power amplifier.
[0030] In some embodiments, each of the first and second power amplifiers may be configured to output a selected one of a constant current power signal, a constant voltage power signal, or a pulsed power signal.
[0031] In some embodiments, the selector may include a number of outputs corresponding to the number of the plurality of first electrodes.
[0032] In some embodiments, the selector can include a number of outputs corresponding to the number of sample wells in the plurality.
[0033] In some embodiments, the first electrodes may be arranged in a format, such as a 96-well plate format or a 384-well plate format, that corresponds to the Society for Biomolecular Screening (SBS) plate format.
[0034] In some embodiments, the plurality of electrodes of the microfluidics system may include between 5 and 500 electrodes, such as between 6 and 300 electrodes, for example, 126 electrodes.
[0035] In some embodiments, the microfluidics system may include an electromechanical assembly configured to move a plurality of first electrodes into contact with respective galvanic contacts of the microfluidic chip.
[0036] In some embodiments, the first electrode of the microfluidics system may be encapsulated in an insulator block that galvanically isolates the electrode.
[0037] In some embodiments, the galvanic contacts of the microfluidic chip of the microfluidics system may include conductive eyelets, and the electrodes may be configured to contact at least a portion of each conductive eyelet.
[0038] In some embodiments, the first electrode of the microfluidics system may include one of more of a pogo pin, a sliding contact, a wire, and / or a probe.
[0039] Another example of a microfluidic system according to the present disclosure may include a microfluidic chip having a non-conductive substrate and sample wells arranged on the non-conductive substrate according to a Society for Biomolecular Screening (SBS) plate format, each sample well having a galvanic contact including a first portion on a top surface of the sample well and a second portion extending into the non-conductive substrate, a plurality of first electrodes each configured to contact the respective galvanic contacts of the microfluidic chip, and at least one second electrode separate from the plurality of first electrodes arranged corresponding to the SBS plate format, first and second power amplifiers each configured to output a different one of a constant current power signal, a constant voltage power signal, or a pulsed power signal, and a selector configured to receive a power signal from the first power amplifier and configured to select at least one of the plurality of first electrodes and output the received power signal thereto. The at least one second electrode may be configured to receive an output of the second power amplifier.
[0040] Another example of a microfluidic system according to the present disclosure may include a microfluidic chip having a non-conductive substrate and sample wells commonly connected to microfluidic channels in the non-conductive substrate, each sample well having a galvanic contact including a first portion on a top surface of the sample well and a second portion extending into the non-conductive substrate, a plurality of electrodes each configured to contact a respective galvanic contact of the microfluidic chip, an electromechanical assembly configured to move the plurality of electrodes into contact with the respective galvanic contact of the microfluidic chip, and a selector configured to receive a power signal from a respective first power amplifier and configured to select at least one of the plurality of electrodes and output the received power signal thereto.
[0041] The present disclosure is not limited to the above examples and aspects, and many other examples and embodiments are provided herein. [Brief description of the drawings]
[0042] [Figure 1A] 1A-1D show various aspects of a microchip electrophoresis configuration in the prior art. [Figure 1B] 1A-1D show various aspects of a microchip electrophoresis configuration in the prior art. [Figure 1C] 1A-1D show various aspects of a microchip electrophoresis configuration in the prior art. [Figure 2A] FIG. 1 is a side view of an electrical interface for microchip electrophoresis according to an embodiment of the present disclosure. [Figure 2B] FIG. 2 is a bottom view of the electrical interface. [Diagram 3] FIG. 3 is a block diagram of components of the electrical interface of FIGS. 2A-B according to an embodiment of the present disclosure. [Figure 4A]4 is a side view illustrating an embodiment of an insulator according to an embodiment of the present disclosure that may be used with the electrical interface of FIGS. 2A-B and 3. FIG. [Figure 4B] 4 is a bottom view showing an embodiment of an insulator according to an embodiment of the present disclosure that may be used with the electrical interface of FIGS. 2A-B and 3. FIG. [Figure 4C] 4A-4C are cross-sectional views illustrating embodiments of insulators according to embodiments of the present disclosure that may be used with the electrical interfaces of FIGS. 2A-B and 3. FIG. [Figure 5A] FIG. 4 is a perspective view of an example of a microfluidics chip according to an embodiment of the present disclosure that may be used in conjunction with the microfluidics chip interface of FIGS. 2A, 2B, and 3. [Figure 5B] FIG. 5B is a cross-sectional view of the microfluidics chip of FIG. 5A. [Figure 5C] FIG. 5C is a perspective view of a conductive islet of the microfluidics chip of FIGS. 5A and 5B. [Figure 5D] FIG. 4 is a perspective view of another example of a microfluidics chip that can be used with the electrical interface of FIGS. 2A-B and 3. [Figure 6A-6B] FIG. 6A is a side view of an electrophoresis device according to an embodiment of the present disclosure including the components of FIGS. 2A-5C in an open or disconnected state, and FIG. 6B is a corresponding side view of the electrophoresis device in a closed or physically connected state. [Figure 6C-6D] FIG. 6C is a side view showing an open or disconnected state of an electrophoresis device according to an embodiment of the disclosure including the microfluidics chip of FIG. 5D, and FIG. 6D is a corresponding side view showing a closed or physically connected state of the electrophoresis device of FIG. 6C. [Figure 7A] FIG. 5 is a side view showing the galvanic contacts of the electrical interface of FIGS. 2A, 2B, and 3 with the microfluidics chip of FIGS. 4A-C, with insulators not shown. [Figure 7B] FIG. 4A-C are side views showing the galvanic contacts of the electrical interface of FIGS. 2A, 2B, and 3 with the microfluidics chip of FIGS. 4A-C. [Figure 8]FIG. 4B is a perspective view of the microfluidics chip of FIGS. 4A-C with a plate holder. [Figure 9] FIG. 9 is a perspective view showing a structure including the components of FIGS. 2A to 5C and 8. [Figure 10] FIG. 13 is a bottom view of an electrical interface according to an aspect of the present disclosure. [Figure 11] 11 is a perspective view of an example of multiple microfluidics chips (or a single larger microfluidics chip) according to an embodiment of the present disclosure that may be used in conjunction with the microfluidics chip interface of FIG. [Figure 12] FIG. 12 is a perspective view showing an arrangement including the components of FIGS. 10 and 11. [Figure 13] FIG. 11 is a block diagram of components of the electrical interface of FIG. 10 according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0043] This disclosure is based in part on the recognition that current microchip electrophoresis interfaces, such as those used in conjunction with the configurations of Figures 1A-1C, may be inadequate for various applications. For example, some current microchip electrophoresis interfaces may not allow for sufficiently long separation channels and may not provide the desired higher resolution, higher separation voltage, and higher throughput sample analysis.
[0044] Thus, the present disclosure provides microchip electrophoresis devices and systems as well as related methods. According to some aspects of the present disclosure, a microfluidic chip having a plurality of sample wells is provided. Additional wells (e.g., reagent wells, waste wells, ladder wells) may also be provided in the microfluidic chip. Each well may be coupled to a microfluidic chip channel in a substrate (e.g., a glass substrate) in the microfluidic chip. Each well of the microfluidic chip may have a respective conductive eyelet. In some embodiments, the conductive eyelet may have a substantially ring shape. Part or all of the top surface of the conductive eyelet may be used as an electrical contact. The conductive eyelet may form all or a portion of the sidewall of the well. The conductive eyelet may receive biological and / or chemical fluids used for electrophoresis therein. A portion of the conductive eyelet may extend into the glass substrate and couple with the microfluidic chip channel therein. The microfluidic chip is configured such that its sample wells may be configured in rows. For example, the arrangement of sample wells may correspond to a Biomolecular Screening Society (SBS) plate format (e.g., a 96-well SBS plate format or a 384-well SBS plate format) for compatibility with standard liquid handling equipment and robotics. Examples of microfluidics chips according to the present disclosure are described in more detail with reference to Figures 5A-5D.
[0045] Some embodiments of the present disclosure provide electrical interfaces that can be used with the microfluidic chips described herein. Embodiments of the electrical interface will now be described with reference to Figures 2A and 2B, which are side and bottom views, respectively, of an electrical interface 100, and Figure 3, which is a block diagram of some of the electrical components of the electrical interface 100.
[0046] The electrical interface 100 may include a controller 102, at least one shared power signal generator 104, at least one independent power signal generator 106, a plurality of electrodes 114, 116, and 118, and at least one selector 110 coupled to the shared power signal generator 104 and between the at least one selector 110 and a portion of the plurality of electrodes 114, 116. In some embodiments, the controller 102, the shared power signal generator 104, the independent power signal generator 106, and the selector 110 may be within a housing 112, although in some embodiments, one or more of these components may be external to the housing 112.
[0047] A plurality of electrodes 114, 116, 118 may be provided. The plurality of electrodes may include sample electrodes 114, each of which may correspond to a sample well of the microfluidics chip. For example, there may be 32 sample wells in the microfluidics chip, and there may be a set of 32 sample electrodes 114, respectively. The plurality of electrodes may include ladder (reference) electrodes 116, each of which may correspond to a ladder well of the microfluidics chip. For example, there may be two ladder wells in the microfluidics chip, and there may be a set of two sample electrodes 116, respectively. Other wells (e.g., reagent wells, wells coupled to separation channels, or waste wells, etc.) may be present in the microfluidics chip, and the plurality of electrodes may have other electrodes 118, each of which may correspond to the other wells. Each of the plurality of electrodes 114, 116, 118 may have a galvanic contact surface configured to contact an electrical contact of the microfluidics chip. In some embodiments, the plurality of electrodes 114, 116, 118 includes pogo pins. In some embodiments, the plurality of electrodes 114, 116, 118 include sliding contacts. In some embodiments, the plurality of electrodes 114, 116, 118 include wires. In some embodiments, the plurality of electrodes 114, 116, 118 include probes. The plurality of electrodes 114, 116, and 118 may be grouped into a first electrode group including the sample electrode 114 and the ladder electrode 116, and a second electrode group including the other electrodes 118, although the disclosure is not limited thereto.
[0048] The plurality of electrodes 114, 116, and 118 may be arranged in a format corresponding to a Society for Biomolecular Screening (SBS) plate format, for example, in a 96-well or 384-well plate format. In other words, the plurality of electrodes 114, 116, 118 may be arranged and spaced apart such that the wells are aligned according to the SBS plate format.
[0049] In some embodiments, the plurality of electrodes 114, 116, 118 can have between 5 and 500 electrodes. In some embodiments, the plurality of electrodes 114, 116, 118 can have between 6 and 300 electrodes. In some embodiments, the plurality of electrodes 114, 116, and 118 can have 42 electrodes or a multiple of 42 (e.g., 126 electrodes).
[0050] As best seen in FIGS. 2A and 2B, in some embodiments, the plurality of electrodes 114, 116, 118 may include extensions that contact the respective contact surfaces of the microfluidics chip. The extensions may be offset and / or non-uniformly arranged. For example, each of the first row 114(1)-114(8) of sample electrodes 114 may be aligned to contact a first portion of the respective contact surface of the microfluidics chip, and each of the second row 114(25)-114(32) of sample electrodes 114 may be aligned to contact a second and different portion of the respective contact surface of the microfluidics chip. In some embodiments, each of the plurality of electrodes 114, 116, and 118 may each contact the same portion of the respective contact surface of the microfluidics chip.
[0051] The shared power amplifier 104 may be a power signal generator, may be controlled by the controller 102, and may be configured to output one or more different power signals. For example, the shared power amplifier 104 may be configured to output a selected one of a constant current power signal having a selected constant current, a constant voltage power signal having a selected constant voltage, or a pulsed power signal having a selected voltage and / or current, a selected duration, and a selected frequency, etc.
[0052] The shared power amplifier 104 may be coupled to a selector 110, which may also be controlled by the controller 102. The selector 110 may have a number of outputs corresponding to the sum of the number of sample electrodes 114 and the number of ladder electrodes 116, although the disclosure is not limited thereto. The selector 110 may receive at its first input (e.g., a power input) a power signal output by the shared power amplifier 104 and at its second input (e.g., a selection input) a selection signal from the controller 102. Based on the selection signal, the selector 110 may select one of the outputs of the selector 110 and communicate the power signal thereto. In some embodiments, the selector 110 may be a multiplexer or a demultiplexer.
[0053] In some embodiments, there may be two or more shared power amplifiers 104 and two or more selectors 110. Each of the multiple selectors 110 may be configured to receive a power signal from a respective one of the multiple power amplifiers and may be configured to output the received power signal to at least a selected one of the multiple electrodes 114, 116.
[0054] Each of the independent power amplifiers 106 may be a power signal generator, may be controlled by the controller 102, and may be configured to output one or more different power signals. For example, each independent power amplifier 106 may be configured to output a selected one of a constant current power signal having a selected constant current, a constant voltage power signal having a selected constant voltage, or a pulsed power signal having a selected voltage and / or current, a selected duration, and a selected frequency, etc. Each independent power amplifier 106 may be coupled (e.g., directly coupled) to one or more electrodes 118 (e.g., one or more other electrodes). Each independent power amplifier 106 may further be controlled by the controller 102. Thus, each of the one or more other electrodes 118 may receive the power signal output by the independent power amplifier 106. In some embodiments, two or more independent power amplifiers 106 may be provided, each driving a different number of electrodes 118.
[0055] With the understanding that the disclosure is not limited thereto, the power amplifiers 104 and 106 may be grouped into a first group including the shared power amplifier 104 and a second group including the independent power amplifier(s) 106.
[0056] Power amplifiers 104 and 106 can output high voltage signals (e.g., on the order of -4000 volts to 4000 volts) and can achieve electrokinetic separation for each sample by creating different constant voltage, constant current, and / or pulsed power signals.
[0057] The controller 102 may include one or more devices configured to perform computational processing. For example, the controller 102 may include one or more processors (e.g., a microprocessor, an ASIC, a microcontroller, or a programmable logic device, etc.). The controller 102 may further include one or more memory devices for storing data and / or instructions to be acted upon by the processor. For example, the memory devices may include dynamic random access memory (DRAM), static random access memory (SRAM), and / or other types of memory. In some embodiments, the instructions stored in the memory of the controller 102 may include one or more program modules or sets of instructions that may be executed by the processor of the controller 102. The controller 102 (and more specifically the processor and its memory) may be configured to control the shared power amplifier 104, the independent power amplifier 106, and the selector 110 to generate one or more power signals and provide the generated power signals to one or more electrodes 114, 116, and 118 of the electrical interface 100.
[0058] 4A, 4B, and 4C are side, bottom, and cross-sectional views, respectively, illustrating an embodiment of an insulator 120. The insulator 120 may be used with the electrical interface 100 and may be on the same side of the housing 112 as the electrodes 114, 116, and 118. The insulator 120 may encapsulate the electrodes 114, 116, and 118 therein, thereby galvanically isolating the electrodes 114, 116, and 118 from one another. As can be seen in FIG. 4C, when the extensions of the electrodes are offset from one another and / or are non-uniform in arrangement, the portions of the insulator 120 that receive the electrodes 114, 116, and 118 may be non-uniform accordingly.
[0059] As discussed above, the electrical interface 100 may be used with microfluidic chips according to some embodiments of the present disclosure. Figure 5A is a perspective view of an example microfluidic chip according to an embodiment of the present disclosure that may be used in conjunction with the microfluidic chip interfaces of Figures 2A, 2B, and 3. Figure 5B is a cross-sectional view of the microfluidic chip of Figure 5A. Figure 5C is a perspective view of a conductive eyelet of the microfluidic chip of Figures 5A and 5B.
[0060] The microfluidics chip 150 may include a non-conductive caddy 151 at least partially surrounding a non-conductive substrate 161 having one or more microfluidics channels 162 therein. The non-conductive substrate 161 may include one or more layers and in some embodiments may include one or more of a cyclic olefin copolymer (COC), a cyclic olefin polymer (COP), quartz, or soda lime glass. In some embodiments, the non-conductive caddy 161 may include, by way of example, acrylic, polyphenylene ether (PPE), polycarbonate, or acrylonitrile butadiene styrene (ABS). In some embodiments, the non-conductive caddy 161 includes an injection molded plastic material.
[0061] The plurality of wells 154, 156, and 158 may extend from a top surface of the non-conductive substrate 161 and each may be fluidly coupled to at least one of the microfluidics channels 162. The plurality of wells 154, 156, and 158 may include sample wells 154 that may each correspond to a sample electrode 114 of the electrical interface 100. For example, there may be 32 sample wells in the microfluidics chip 150, and there may be a set of 32 sample electrodes 114 respectively. The plurality of electrodes may include ladder (reference) wells 156 that may each correspond to a ladder electrode 116 of the electrical interface 100. For example, there may be two ladder wells 156 in the microfluidics chip 150, and there may be a set of two ladder electrodes 116 respectively. Other wells 158 (e.g., reagent wells, wells coupled to separation channels, or waste wells, etc.) may be present in the microfluidics chip 150, and the plurality of electrodes may have other electrodes 118 that each correspond to the other wells 158, as discussed above. Similar to the plurality of electrodes 114, 116, and 118, the plurality of wells 154, 156, and 158 may be grouped into a first well including sample well 154 and ladder well 156 and a second well including other wells 158, although the disclosure is not limited thereto.
[0062] Each of wells 154, 156, and 158 may have a galvanic contact on its top surface. For example, non-conductive caddy 151 may be formed such that non-conductive outer wells 152 are formed, each outer well 152 may have a conductive eyelet 163 therein having sidewalls 165, as best seen in FIG. 5C. In some embodiments, the conductive eyelets may be fused to outer wells 152. Conductive eyelets 163 may have a ring shape in some embodiments, although the disclosure is not limited thereto. Conductive eyelets 163 may have a first galvanic contact portion at the top surface of the corresponding well and a second galvanic contact portion 167 that extends into the non-conductive substrate. In some embodiments, the first portion of the galvanic contact includes the entire portion of the annular eyelet. In some embodiments, the second galvanic contact portion 167 that extends into the non-conductive substrate 161 is a portion of the annular body. In some embodiments, the conductive eyelet 163 and / or its galvanic contacts comprise a conductive carbon-based material.
[0063] Figure 5D is a perspective view of another example of a microfluidics chip 150' that can be used with the electrical interfaces of Figures 2A-B and 3. As can be seen in Figure 5D, the microfluidics chip 150' can include a carrier 155 that surrounds and insulates the wells 154, 156, and 158. In some embodiments, the top surfaces of the wells 154, 156, and 158 can be flush with the top surface of the carrier 155.
[0064] According to some aspects of the present disclosure, a microfluidic chip 150 is provided having a plurality of sample wells 154. Additional wells 156 and 158 (e.g., reagent wells, waste wells, ladder wells) may also be provided in the microfluidic chip 150. Each well may be coupled to a microfluidic chip channel 162 in a non-conductive substrate 161 (e.g., a glass substrate) in the microfluidic chip 150. Each well of the microfluidic chip may have a respective conductive eyelet 163. In some embodiments, the conductive eyelet 163 may have a substantially ring shape. Part or all of the top surface of the conductive eyelet 163 may be used as an electrical contact. The conductive eyelet 163 may form all or a portion of the sidewall 165 of the well.
[0065] The conductive eyelet 163 may receive therein biological and / or chemical fluids used for electrophoresis. A portion 167 of the conductive eyelet 163 extends into the non-conductive substrate 161 and may interface therewithin with a microfluidic chip channel 162.
[0066] As discussed above, in some embodiments, microfluidic chip 150 may be configured such that its wells 154, 156, and 158 may be arranged in rows. For example, the arrangement of wells 154 may correspond to a Society for Biomolecular Screening (SBS) plate format (e.g., a 96-well SBS plate format or a 384-well SBS plate format). In some embodiments, microfluidic chip 150 may conform to ANSI SLAS 1-2004 (R2012) dimensions and / or ANSI SLAS 4-2004 (R2012) dimensions.
[0067] Figure 6A is a side view of an electrophoresis device or system according to an embodiment of the disclosure including the components of Figures 2A-5C in an open or disconnected state, and Figure 6B is a corresponding side view of the electrophoresis system in a closed or physically connected state. Figures 7A and 7B are side views of the galvanic contacts of the electrical interface of Figures 2A, 2B, and 3 with the microfluidics chip of Figures 4A-C in a closed or connected state (e.g., as in Figure 6B), with insulator 120 not shown in Figure 7A.
[0068] In view of the above, and with reference to FIGS. 6A-7B, an embodiment of the present disclosure provides a microfluidic system 130 having a microfluidic chip 150 having a plurality of wells (e.g., sample well 154, ladder well 156, and other wells 158) with respective galvanic contacts 163 on an upper surface thereof. A plurality of electrodes (e.g., sample electrode 114, ladder electrode 116, and other electrodes 118) may be provided as part of the electrical interface 100. Each electrode may be configured to contact a respective one of the galvanic contacts of the microfluidic chip 150. One or more shared power amplifiers 104 and independent power amplifiers 106 may be provided as part of the electrical interface, each of the one or more shared power amplifiers 104 and independent power amplifiers 106 configured to output a respective power signal. A selector 110 that is part of the electrical interface 100 may be configured to receive a power signal from the shared power amplifier 104 and to output the received power signal to at least one selected electrode of the plurality of electrodes. At least one other electrode may be configured to receive the power signal output by the independent power amplifier 106 .
[0069] Each of the one or more shared power amplifiers 104 and independent power amplifiers 106 may be configured to output a selected one of a constant current power signal, a constant voltage power signal, or a pulsed power signal. The power amplifiers 104 and 106 may output high voltage signals (e.g., on the order of -4000 volts to 4000 volts) and may accomplish electrokinetic separation for each sample by producing different constant voltage, constant current, and / or pulsed power signals.
[0070] In some embodiments, the microfluidic system 130 may include an electromechanical assembly 180 configured to move the electrodes into contact with respective contacts of the microfluidic chip. For example, the microfluidics chip 150 may be raised into contact with the electrodes of the electrical interface 100, or the electrical interface 100 and insulator 120 may be lowered into contact.
[0071] 6A-7B show the microfluidics chip 150 of FIG. 5A, it should be understood that the microfluidics chip 150' of FIG. 5D may also be used in a microfluidics system 130' including an electromechanical assembly 180 configured to move a plurality of electrodes into contact with respective contacts of the microfluidics chip 150', as seen in FIGS. 6C and 6D. In some embodiments, the insulator 120 used with the microfluidics chip 150' may be different than the insulator 120 used with the microfluidics chip 150 of FIG. 5A. For example, the insulator 120 used with the microfluidics chip 150' may compress and / or abut against a top surface of the microfluidics chip 150' of FIG. 5D. The insulator 120 used with the microfluidics chip 150 of FIG. 5A may have a bottom surface that extends below a top surface of the microfluidics chip 150 (e.g., to cover a portion of the vertical height of each of the sample wells of the microfluidics chip 150).
[0072] FIG. 8 shows a perspective view of the microfluidics chip of FIGS. 4A-C with a plate holder 170. The plate holder 170 can include a slot or groove 171 therein configured to receive the microfluidics chip 150. In some embodiments, the microfluidics chip 150 can be integral with the plate holder 170. The plate holder 170 can further provide compatibility with standard liquid handling equipment and robotics. Although not shown, it should be understood that the plate holder 170 can also be used with the microfluidics chip 150' of FIG. 5D.
[0073] 9 is a perspective view showing an arrangement including the components of FIGS. 2A-5C and 8. In some embodiments, the electromechanical assembly 180 may be configured to move a plurality of electrodes into contact with respective contacts of a microfluidic chip 150 mounted within a plate holder 170. As discussed above, the plate holder 170 with the microfluidics chip 150 mounted therein may be raised into contact with the electrodes of the electrical interface 100, or the electrical interface 100 and insulator 120 may be lowered into contact.
[0074] For example, it should be understood that the configurations of Figures 2A and 2B are merely examples and that further parallel processing of samples may be provided in accordance with embodiments of the present disclosure. For example, Figure 10 is a bottom view of an electrical interface 200 according to an embodiment of the present disclosure. Figure 11 is a perspective view of an example of multiple microfluidics chips (or a single larger microfluidics chip) according to an embodiment of the present disclosure that may be used in conjunction with the microfluidics chip interface of Figure 10. Figure 12 is a perspective view showing a microfluidic system 230 including the components of Figures 10 and 11. Figure 13 is a block diagram of the components of the electrical interface 200 of Figures 10 and 120 according to an embodiment of the present disclosure. Although not shown, the embodiments of Figures 10-13 may be used in conjunction with the microfluidics chip 150' of Figure 5D.
[0075] The electrical interface 200 can include multiple sets of electrodes (designated A, B, and C in FIGS. 10 and 13), each set corresponding to FIGS. 2A and 2B, and thus each set corresponding to multiple wells of the microfluidics chip 150. Although three sets are depicted in FIGS. 10 and 13, other numbers of sets may be provided in accordance with the inventive concepts disclosed herein.
[0076] Each set of electrodes may include a plurality of electrodes 214, 216, 218. The plurality of electrodes may include sample electrodes 214, each of which may correspond to a sample well of the microfluidics chip. For example, there may be 96 sample wells (each grouped into three sets of 32 sample wells) in the microfluidics chip, and there may be respective sets of 96 sample electrodes 214. The plurality of electrodes may include ladder (reference) electrodes 216, each of which may correspond to ladder wells of the microfluidics chip. For example, there may be 6 ladder wells (each grouped into three sets of 2 ladder wells) in the microfluidics chip, and there may be respective sets of 6 ladder electrodes 216. Other wells (e.g., reagent wells, wells coupled to separation channels, or waste wells, etc.) may be present in the microfluidics chip, and the plurality of electrodes may have other electrodes 218, each of which may correspond to other wells. As discussed above, each of the plurality of electrodes 214, 216, 218 can have a galvanic contact surface configured to contact electrical contacts of the microfluidic chip. In some embodiments, the plurality of electrodes 214, 216, 218 can include one or more of pogo pins, sliding contacts, wires, and / or probes. The plurality of electrodes 214, 216, and 218 can be grouped into a first set of electrodes including the sample electrode 214 and the ladder electrode 216, and a second set of electrodes including the other electrodes 218, although the disclosure is not limited thereto.
[0077] The arrangement of electrodes 214, 216, and 218 of Figure 10 may be used in conjunction with multiple microfluidics chips 150 (or a single larger microfluidics chip 250), as can be seen in Figure 11. A plate holder 270 may include multiple grooves or slots 271 therein, each groove or slot 271 configured to receive a respective microfluidics chip 150. In some embodiments, the microfluidics chip 150 (or the single larger microfluidics chip 250) may be integrated into the plate holder 270.
[0078] 13, electrical interface 200 may be similar to electrical interface 100 previously described and may include a controller 202, at least one shared power signal generator 204, at least one independent power signal generator 206, a plurality of electrodes 214, 216, and 218, and at least one selector 210 coupled to shared power signal generator 204 and between the at least one selector 210 and a portion of the plurality of electrodes 214, 216. In some embodiments, controller 202, shared power signal generator 204, independent power signal generator 206, and selector 210 may be within housing 212, although in some embodiments, one or more of these components may be external to housing 112.
[0079] The microfluidic system 230 may have a plurality of microfluidic chips 150 having a plurality of wells (e.g., sample well 154, ladder well 156, and other wells 158) with respective galvanic contacts 163 on their upper surfaces. A plurality of electrodes (e.g., sample electrode 114, ladder electrode 116, and other electrodes 118) may be provided as part of the electrical interface 200. Each electrode may be configured to contact a respective one of the galvanic contacts of the microfluidic chip 150. One or more shared power amplifiers 204 and independent power amplifiers 206 may be provided as part of the electrical interface, and each of the one or more shared power amplifiers 204 and independent power amplifiers 206 may be configured to output a respective power signal. A selector 210 that is part of the electrical interface 100 may be configured to receive a power signal from the shared power amplifier 104 and to output the received power signal to at least one selected electrode of the plurality of electrodes. In some embodiments, the received power signal may be output to a plurality of electrodes, each corresponding to a respective microfluidic chip 150. At least one other electrode for at least one of the microfluidics chips 150 may be configured to receive the power signal output by the independent power amplifier 206 .
[0080] Power amplifiers 204 and 206 can output high voltage signals (e.g., on the order of -4000 volts to 4000 volts) and can achieve electrokinetic separation for each sample by creating different constant voltage, constant current, and / or pulsed power signals.
[0081] The inventive concepts have been described above with reference to the accompanying drawings. The inventive concepts are not limited to the illustrated embodiments, but rather, these embodiments are intended to fully and completely disclose the inventive concepts to those skilled in the art. In the drawings, like numbers refer to like elements throughout. Thicknesses and dimensions of some elements may not be drawn to scale.
[0082] Spatially relative terms such as "below," "below," "down," "on," "above," "on top," and "at the bottom of" may be used herein to facilitate description to describe the relationship of one element or feature to another element(s) or feature(s) as shown in the drawings. It will be understood that the spatially relative terms are intended to encompass different orientations of the device during use or operation in addition to the orientation depicted in the drawings. For example, if a device in the drawings is inverted, an element described as "below" or "directly below" another element or feature would be oriented "above" the other element or feature. Thus, the exemplary term "below" can encompass both an orientation above and below. The device may be oriented in another direction (rotated 90 degrees or in another orientation) and the spatially relative descriptors used herein interpreted accordingly.
[0083] Well-known functions or structures may not be described in detail for brevity and / or clarity. As used herein, the expression "and / or" includes all combinations of one or more of the associated listed items.
[0084] It will be appreciated that aspects of all of the embodiments disclosed herein may be combined in different ways to provide numerous further embodiments. Thus, it will be appreciated that elements discussed above with respect to one particular embodiment may be incorporated, alone or in combination, in any of the other embodiments.
[0085] It will be understood that terms such as first, second, etc. may be used herein to describe various elements, and that these elements should not be limited by these terms. These terms are used only to distinguish one element from another. For example, a first element may be referred to as a second element, and similarly, a second element may be referred to as a first element, without departing from the scope of the inventive concept.
Claims
1. Multiple electrodes, each including a galvanic contact surface configured to contact each contact portion of the microfluidic chip, A shared power amplifier configured to output a selected first power signal, A selector configured to receive the first power signal from the shared power amplifier and to output the received power signal to one or more selected electrodes from the plurality of electrodes, An electrophoretic device equipped with [a specific feature].
2. The electrophoretic device according to claim 1, wherein the plurality of electrodes are a plurality of first electrodes, and the electrophoretic device further comprises at least one independent power amplifier configured to output a selected second power signal to at least one second electrode separate from the plurality of first electrodes.
3. The electrophoretic device according to claim 1, wherein the shared power amplifier is configured to output one selected from a constant current power signal, a constant voltage power signal, or a pulsed power signal as the first power signal.
4. The electrophoresis device according to claim 1, wherein the plurality of electrodes include a plurality of sample electrodes and a plurality of ladder electrodes, and the selector includes a number of outputs corresponding to the sum of the number of sample electrodes and the number of ladder electrodes.
5. The electrophoretic device according to claim 1, wherein the electrodes are arranged in a format corresponding to the plate format of the Society for Biomolecular Screening (SBS).
6. The electrophoresis device according to claim 5, wherein the plate format of the SBS is a 96-well plate format.
7. The electrophoresis device according to claim 5, wherein the plate format of the SBS is a 384-well plate format.
8. The electrophoretic device according to claim 1, wherein the plurality of electrodes have between 5 and 500 electrodes.
9. The electrophoretic device according to claim 8, wherein the plurality of electrodes have between 6 and 300 electrodes.
10. The electrophoretic device according to claim 9, wherein the plurality of electrodes have 126 electrodes.
11. The electrophoretic device according to claim 1, further comprising an electromechanical assembly configured to move the plurality of electrodes so as to contact the respective contact portions of the microfluidic chip.
12. The electrophoretic device according to claim 1, wherein the electrode is enclosed within an insulating block that galvanically insulates the electrode.
13. The electrophoretic device according to claim 1, wherein the contact portion of the microfluidic chip includes a conductive eyelet, and the electrode is configured to contact at least a portion of each of the conductive eyelets.
14. The electrophoretic device according to claim 1, wherein the electrode includes a pogo pin.
15. The electrophoretic device according to claim 1, wherein the electrode includes a sliding contact portion.
16. The electrophoretic device according to claim 1, wherein the electrode includes a wire.
17. The electrophoretic device according to claim 1, wherein the electrode includes a probe.
18. A plurality of first electrodes, each including a galvanic contact surface configured to contact each contact surface of a microfluidic chip, Separate from the plurality of first electrodes, at least one second electrode includes a galvanic contact surface configured to contact each of the contact surfaces of the microfluidic chip, A first power amplifier configured to output one selected from a constant current power signal, a constant voltage power signal, or a pulsed power signal as a first power signal, A selector configured to receive the first power signal from the first power amplifier, to select at least one of the plurality of first electrodes, and to output the received first power signal to it, A second power amplifier is configured to output to at least one second electrode a second power signal, which is selected from a constant current power signal, a constant voltage power signal, or a pulsed power signal, and is different from the output of the first power amplifier. An electrophoretic device equipped with [a specific feature].
19. The electrophoretic device according to claim 18, wherein the selector includes a number of outputs corresponding to the number of the plurality of first electrodes.
20. A plurality of electrodes arranged in accordance with the plate format of the Society for Biomolecular Screening (SBS), each electrode including a galvanic contact surface configured to contact each contact surface of a microfluidic chip having sample wells arranged in the SBS plate format, First and second power amplifiers, each configured to output one different signal from a constant current power signal, a constant voltage power signal, or a pulsed power signal, A selector configured to receive a power signal from the first power amplifier, and to select at least one of the plurality of electrodes and output the received power signal to it, An electrophoretic device equipped with [a specific feature].
21. The electrophoresis device according to claim 20, wherein the plate format is a 96-well or 384-well plate format.
22. The electrophoretic device according to claim 20, further comprising an electromechanical assembly configured to move the plurality of electrodes so as to contact the respective contact surfaces of the microfluidic chip.