Smart microfluidic mixing equipment and cartridges

Abstract

The present invention provides a "smart" device (100) for mixing, a microfluidic chip (50), and a system in which they are used to prepare formulations. [Solution] The microfluidic chip includes microchannels and programmable data components. This system enables even beginners to achieve optimal formulations of RNA, antisense, peptides, and small molecules.

Description

Technical Field

[0001] The field of the present invention is small volume mixers for research materials and formulations.

Background Art

[0002] Microfluidic mixing incorporates the physical properties of fluids flowing through fine channels to promote the self-assembly of nanoparticles that can efficiently encapsulate nucleic acids, small molecules, proteins and / or peptides while minimizing the loss of delicate and expensive materials. The resulting formulations are useful for academic research and medical treatments.

[0003] U.S. Patent Application Publication Nos. 20120276209 and 20140328759 by Cullis et al. describe methods using small volume mixing techniques and the novel formulations thereby induced. U.S. Patent Publication No. 20160022580 by Ramsay et al. describes recent advances using small volume mixing techniques and products.

[0004] In recent years, devices for biological microfluidic mixing have been designed. Precision NanoSystems Inc. in Vancouver, Canada manufactures and sells such devices under the brand name NanoAssemblr®. Disposable cartridges or microfluidic chips (hereinafter, "m-chips") are small laboratory mixing platforms that function within these devices and are small laboratory mixing platforms that function within these devices.

[0005] Currently, the control of the mixing process on the m-chip is performed by an operator through a mechanical control or manual operation mechanism. Under the instructions of an operator or "user", these dispense reagents at the inlet of the m-chip at an optimal rate to achieve optimal mixing.

[0006] The fluid elements to be mixed by researchers are becoming increasingly complex and valuable, including nucleic acids, peptides, and small molecule drugs. In the laboratory and in personalized medicine, for each drug and tissue target To better understand which lipid / surfactant / drug ratio and particle size are optimal, it is necessary to prepare and screen numerous formulations under specific conditions, each of which must be carefully tracked. Furthermore, because m-tips are so small, users cannot easily determine whether they are clean, uncontaminated, or whether their free flow is inhibited or blocked. [Overview of the project] [Problems that the invention aims to solve]

[0007] There is a need for a semi-automated, quality-controlled microfluidic mixing system that minimizes the loss of expensive materials and enables consistently high-quality formulations regardless of the user's experience level. [Means for solving the problem]

[0008] According to embodiments of the present invention, a mixing apparatus is provided having a motor, a pump, a microfluidic chip engagement tray incorporating a data transmitter / receiver, a microcontroller, and a user interface. In one embodiment, the data transmitter / receiver includes an RFID reader. In another embodiment, the transmitter / receiver detects the correct positioning of the microfluidic chip on the engagement tray.

[0009] In another embodiment, the device operates in conjunction with a microfluidic chip that includes data components.

[0010] In another embodiment of the present invention, the device and the microfluidic chip communicate with each other when the microfluidic chip engages with the device and the device is powered on.

[0011] According to one embodiment of the present invention, a programmable microfluidic chip is provided that includes an inlet, a microchannel, an outlet, and a data component.

[0012] In another embodiment of the present invention, a microfluidic chip according to claim 1 is disclosed, wherein the data component is a radio frequency identification tag ("RFID"). In another embodiment, the RFID has a defined readable range. In some embodiments, the range is 0 to 50 mm. In another embodiment, the range is 0 to 20 mm. In another embodiment, the range is 0 to 5 mm. In another embodiment of the present invention, the microfluidic chip comprises a removable mating manifold and a cover.

[0013] In another embodiment of the present invention, the data component is readable by a mixing instrument and includes stored data that indicates its behavior. In another embodiment of the present invention, the stored data includes a state indicator that includes historical data of the microfluidic chip.

[0014] In another embodiment of the present invention, the stored data includes the type or purpose of the microfluidic chip.

[0015] In another embodiment of the present invention, the data component is readable by the instrument for mixing, processed by a microcontroller within the instrument, and the corresponding message is communicated to the user via a user interface on the instrument.

[0016] In another embodiment of the present invention, data read from a data component instructs the device on what information to transmit to the user interface.

[0017] In another embodiment of the present invention, data is read from the data component of a microfluidic chip. The collected data is sent to the user interface and includes information that is displayed to the user as a set of instructions. In another embodiment, the information is displayed to the user as a set of options.

[0018] In another embodiment of the present invention, a data component can receive, store, and transmit data.

[0019] According to an embodiment of the present invention, there is provided a system for formulating a therapeutic agent for research use, including a pump, a microfluidic chip engagement tray incorporating a data transmitter / receiver, a microcontroller, a memory storage device, and a user interface, and a device having a replaceable microfluidic chip, wherein the therapeutic agent is selected from the group consisting of nucleic acids, peptides, proteins, or hydrophobic small molecules.

[0020] Other aspects and features of the present invention will become apparent to those skilled in the art upon consideration of the following description of specific embodiments of the present invention in conjunction with the accompanying drawings.

Brief Description of the Drawings

[0021] [Figure 1] A perspective view of a microfluidic mixing device according to an embodiment of the present invention. [Figure 2A] A perspective view of an embodiment of a microfluidic chip as used in a Spark® microfluidic mixing device. [Figure 2B] A perspective view of another embodiment of a microfluidic chip as used in a Spark® microfluidic mixing device. [Figure 2C] A perspective view of an embodiment of a microfluidic chip for use in a benchtop device. [Figure 3] A flowchart showing the direction of information traveling between a data transmission sensor tag and a data reader, and the resulting actions performed by the mixing device. The thick line indicates the process flow, and the thin line indicates the data flow (the arrows indicate the direction). [Figure 4A] A diagram showing the size ratio of an RFID tag on an M-chip and each data signal range regarding the reader. The range of the readable height and the signal height is indicated by a broken line, and the readable range of the underlying reader is shown as a long rectangle. [Figure 4B]FIG. Another embodiment of the arrangement of RFID tags with respect to a reader and data signals (RFID tags with respect to the reader and data signals). The range of the readable height and the signal height is indicated by a dashed line. [Figure 4C] FIG. Another embodiment of an RFID tag with respect to a reader and data signals (of an RFID tag with respect to the reader and data signals). The range of the readable height and the signal height is indicated by a dashed line, but in reality it is not rectangular but oval. [Figure 5A] FIG. Layout diagram of the main PCB, microcontroller, data transmitting sensor reader, and connectors within the range of the outer shape of an embodiment of a microfluidic mixing device as seen from the front of the device. [Figure 5B] FIG. An element identical to that shown in FIG. 5A, but a view seen from the right side of the device. [Figure 6] FIG. Electrical system block diagram showing the functional units inside a microfluidic mixing device. The components are shown by solid lines and the installation area of the device is shown by a dashed line. [Figure 7] A series of photographs of the graphical user interface displayed on a Spark (registered trademark) microfluidic mixing device depicting a greeting screen, a user control mode 1 screen, a mode 2 screen for a predetermined flow rate ratio kit, and a "completed" screen indicating that the formulation is complete.

DETAILED DESCRIPTION OF THE INVENTION

[0022] According to a first embodiment of the present invention, a microfluidic mixing device as schematically shown in FIG. 1 is provided. The microfluidic mixing device includes a rigid shell case 85 having a front surface 95, a graphical user interface such as a screen or a touch screen 90, a start button 87, an M-chip entry 82, and a platform 115 with a pressure sensor.

[0023] As best shown in the block diagram Figure 6, which illustrates the mechanical and electrical elements and their relationships, the device 100 houses a clamp motor 60 and a pump motor 62 connected to a main printed circuit board (main "PCB") via a cable 70. The main PCB 340 occupies space within a rigid shell case 85 near the rear of the device 100, behind the pump(s) 47.

[0024] The power switch and jack 64, as well as the power supply 65, are also connected to the PCB 340 via cable 70. One or more independent inlet pumps 47 (not shown) and m-tip engagement clamps, as well as a bite seal (not shown, but which descends to the m-tip at startup), are mechanically connected to motors 62 and 60.

[0025] Figures 5A and 5B are a front and side cross-sectional view and a side cross-sectional view of the device 100, showing the locations of the main PCB 340, microcontroller 300, and connector 112 in one embodiment. Figure 5B shows the locations of the leader 110 and secondary PCB 112.

[0026] The reader 110 and the secondary PCB 112 are connected to the main PCB 340 via the ribbon cable connector 68. The secondary PCB 112 operates the LED associated with the m-chip entry 82. The cartridge switch 67 and the start switch 66 are also connected to the secondary PCB 112. The cartridge switch 67 engages with the reader 110. The cartridge switch 66 engages with the start button 87.

[0027] The secondary PCB 112 is typically located at the bottom of the device 100, beneath the platform 115. Referring here to Figure 5a, the general positions of the components are shown only in relation to their positions relative to the outline of the device 100, as viewed from the front. The reader 110 is shown below the m-chip entry 82.

[0028] In a preferred embodiment, an on / off power switch is located at the rear of the device 100.

[0029] The data transmission sensor 20 interacts with the reader 110 of the device 100 to check whether a cartridge is to be used, and if not, notifies the user whether the cartridge is compatible with the device 100, loads a recipe, prompts the user for confirmation, executes the process if the user indicates "yes", indicates the result of success or error, and completes the process of recording usage data on a tag.

[0030] The microcontroller 300 (for example, a microcontroller such as the ATmega2560® microcontroller, available from any robot vendor including http: / / www.canadarobotix.com, www.BC-Robotics.com, and https: / / www.buyapi.ca) coordinates and controls commands and feedback between other components. In embodiments, the microcontroller 300 is a single-board microcontroller used to build digital devices and interactive objects that can sense and control real-world objects. The main PCB 340 receives and distributes commands and feedback between other components. The microcontroller 300 is typically located in front of the PCB 340 and behind the front of the device 95.

[0031] A preferred embodiment includes one or two motors, which are shown in block diagram form in Figure 6. Only the state is shown. The clamp motor 60 operates to lower an independent inlet pump 47 to the inlet 55 or the cover of the mounted m-tip 50. The pump motor 62 moves the pump plunger or piston at a predetermined speed. The pump mechanism(s) is, in a preferred embodiment, a direct pump, which pumps the propellant fluid under controlled pressure through the precisely sealed m-tip 50, as described below. The linear travel per step is the most important specification for the motors. The value for the clamp motor 60 is 0.0003125” / step (0.0079 mm / step), and the motor value for the pump motor 62 is 0.00125” / step (0.0317 mm / step).

[0032] Data Components According to a second embodiment of the present invention, an m-chip 50 according to the present invention is provided, as illustrated by the embodiments shown in Figures 2A, 2B, and 2C.

[0033] The M-tip 50 is made of a solid material such as rigid or semi-rigid plastic, metal, or glass, and is manufactured to have an inlet 55, a microchannel having a micromix shape, an outlet 45, and a data component 20. In some embodiments of a special lid that is placed on the M-tip 50 after the reagent has been added to the inlet 55, the M-tip 50 has a clamp that secures it in place and an inlet pump 47 (not shown) that has the strength and surface to seal the inlet 55. In some embodiments, the M-tip has side flanges 52 for stability and user operation. These are not necessary for the operation of the M-tip but are added for user convenience. When properly positioned within the instrument 100, the microchannel of the M-tip 50 is fluid pressure connected to the instrument's pump(s) 47 (shown, e.g., Figure 2A) that propels the flow of reagent from the inlet 55 to the microchannel via positive displacement or by controlled pressurization of an inlet reservoir 55 integrated inside the tip 55. In one embodiment, one syringe pump is used per inlet. In some embodiments, there are two inlets 55, and the reagents from each inlet 55 are engaged by separate pumps so that they are driven separately (for example, at different speeds).

[0034] As described above, the M tip 50 in Figures 4A, 4B, and 4C includes, in a preferred embodiment, an inlet 55 having two wells for dispensing fluid elements and at least one outlet 45. The fluid elements for mixing may be lipids, surfactants, water-soluble and water-insoluble materials for formulations, buffers, and excipients. The operator or equipment draws the resulting mixture from the outlet 45 into a suitable container.

[0035] Hydraulics (or water pressure / fluid pressure / hydraulics) In one embodiment, one syringe pump is used for each inlet. In some embodiments, there are two inlets 55, which are engaged by separate pumps so that the reagents from each inlet 55 are driven separately (for example, at different speeds).

[0036] A microchannel is defined as a channel having a hydraulic diameter of less than 1 mm. “Mixed geometry” is known in the art and includes herringbone and other patterned microchannels, examples of which are disclosed in U.S. Patent Publication Nos. US20120276209A1, US20160214103A1, US20160235688A1, and PCT Publication WO2016138175A1. In some embodiments, the data component 20 is placed within a tag recess 25 in the m-chip 50 to reduce the risk of tampering or corruption. “Mixed” means any action in which two or more materials are combined.

[0037] Data transmission sensor The data transmission sensor 20 is embedded in or bonded to the m-chip 50, has a sensitivity range 80, and interacts with the data receiver 110. The source of information for the data transmission sensor is optional. It is an online electronics vendor. The tag 20 is programmed using a simple computer language and, in some embodiments, is manually installed on the m-chip 50. In an alternative embodiment, the tag 20 is fabricated on the m-chip and programmed after fabrication. In another embodiment, the tag 20 is pre-programmed and then fabricated on the m-chip.

[0038] In a preferred embodiment, the data transmission sensor 20 is an RFID tag.

[0039] Generally, RFID tags or radio frequency identification tags are embedded together with a transmitter and receiver. An RFID component according to an embodiment of tag 20 has a chip for storing and processing information and an antenna for transmitting and receiving signals. The tag may encode a unique serial number of a particular m-chip 50 and have certain characteristics programmed into it.

[0040] In some embodiments of the present invention, the RFID tags 20 are passive in that they use the reader's radio energy to relay the data they store back to the reader 110. In other embodiments, a small battery for information relay is embedded in the powered tag.

[0041] The interaction between the tag 20 and the microfluidic mixing device is integrated within the operating device 100, as is generally shown in Figures 4A, 4B, and 4C regarding the external shape of the reader 110. The range 80 of each tag 20 is customized for the operating device 100. The area that the data-emitting sensor tag must be positioned to be successfully read is indicated by the dashed line representing 80, i.e., the signal range. The 4.5 mm vertical distance between the reader and the tag is not evident from Figure 4A, but this distance works well with the 7.5 mm size tag shown and affects the signal range 80. This embodiment is useful for the smallest device 100.

[0042] Figure 4B shows a corresponding 7.5 mm RFID tag (with label) and an RFID reader module 110 that can be integrated into the operating device. In this example, the readable area is reduced by increasing the vertical distance between the reader and the task to 6.7 mm.

[0043] The interaction between the tag 20 and the microfluidic mixing device, as generally shown in Figures 4A, 4B, and 4C, is integrated within the operating device 100. The area where the data-transmitting sensor tag must be positioned for successful reading is indicated by a dashed line representing the signal range 80. The 4.5 mm vertical distance between the reader and the tag, not evident from Figure 4A, works for the 7.5 mm size tag shown and affects the signal range 80. This embodiment is useful for the smallest device 100.

[0044] Figure 4B shows a corresponding 7.5 mm RFID tag (with label) and an RFID reader module 110 that can be integrated into the operating device. In this example, the readable area is reduced by increasing the vertical distance between the reader and the task to 6.7 mm.

[0045] Figure 4C shows an embodiment of the m-chip 50 used in a higher-capacity device (NanoAssemblr® desktop) than the m-chip shown in Figures 4A and 4B, which is designed for Spark®, a small-capacity mixer. The main functions are identical in the three embodiments 4A, 4B, and 4C shown. Since the desktop reader 110 has a different receiving area, the tag 20 is larger in the embodiment shown in Figure 2C, as is also reflected in Figure 4C.

[0046] In some embodiments, the interaction between the tag 20 and the reader 110 is unidirectional, or in preferred embodiments, bidirectional. Figure 3 is a flowchart showing the queries and communications between the data-transmitting sensor 20 on the m-chip 50 and the reader 110, and what information is conveyed to the graphical user interface 90. The rightmost column of the flowchart shows the characteristics of the data-transmitting sensor 20. In particular, the control and adjustment in the middle column of the operation in Figure 3 is performed by a microcontroller 300 that commands the main PCB 340. The microcontroller 300 communicates with and adjusts the graphical user interface (GUI) 90, and receives feedback from the GUI on the platform 115, as well as from the pressure sensor 115, the start button 87, and the motors 60 and 62.

[0047] In one embodiment, the data transmission sensor 20 may include data in the form of an integer count, binary flag, defined character, string, or equivalent indicating whether it has been used before, and if so, how many times it has been used, or how many uses remain. Such applications are useful when the number of uses, including disposable use of the m-chip 50, must be implemented for regulatory or licensing reasons. Particularly in microfluidics, the presence of tiny channels that are not easily visible can lead to a situation where the m-chip 50 appears "uncontaminated" and usable by the operator, but in reality contains substances (such as nucleic acids, salts, proteins, or other molecules) that exhibit cross-contamination between runs. In addition, using the m-chip 50 can cause microscopic damage invisible to the operator, impairing subsequent experiments performed on the device 50.

[0048] In one embodiment, the m-chip 50 may include means for storing a set of instructions for the instrument to execute on the inserted m-chip 50. This may include instrument settings such as temperature, delay time, pressure value, or any other parameters that can be incorporated into an electromechanical instrument. In one embodiment, after the m-chip 50 is inserted into the instrument, the recipe will be read and executed (with or without user prompts or warnings). Such a configuration would be appealing in many scenarios. In some situations, a manufacturer may supply the m-chip 50 as part of a larger kit in which different kits may use the same m-chip to perform different tasks. In this situation, the stored recipes would allow the manufacturer to produce only one type of m-chip 50, but load different recipes depending on which kit it is bundled with. This approach reduces the possibility of errors compared to an approach in which the operator must input or select a recipe on the instrument. In addition, this approach allows the manufacturer to update recipes or release new recipes without having to perform updates for the instruments deployed in the field. In further embodiments, the m-chip 50 may include multiple recipes, each having a corresponding feature recognized by the device, and thus the m-chip 50 is backward compatible and interoperable with devices containing different software or hardware versions.

[0049] Therefore, in the embodiment, recording of usage data can be achieved using a writable RFID tag 20 which includes a defined storage area of ​​memory having a flag that the device 100 can switch on to indicate that the m-chip 50 has been used. If reuse is permitted a certain number of times under certain licensing or regulatory conditions, the memory block is used to store how many more times the m-chip 50 will be used or how many uses remain.

[0050] In embodiments of the present invention, the RFID tag 20 includes a memory for storing a set of instructions for the device to execute on the inserted m-chip 50. This may include device settings such as temperature, delay time, pressure value, flow rate, actuator travel speed, travel distance, or other parameters that can be incorporated into an electromechanical device. In one embodiment, the m-chip After the P50 is inserted into the microfluidic mixing instrument, the recipe will be read and executed with or without further user intervention. In such embodiments, to avoid errors and simplify the operator's workflow, one or more embedded or pre-loaded reagents may be provided in the cartridge, in which the corresponding recipe can be programmed.

[0051] This approach reduces the possibility of user error. In addition, the system of the present invention allows manufacturers to update recipes or release new recipes without having to perform updates on equipment deployed in the field. In a further embodiment, the m-chip 50 may contain multiple recipes, each having corresponding features recognized by the equipment 100, and may even be backward compatible or interoperable with equipment containing different versions of software or hardware.

[0052] In one embodiment, the device 100 records data on the m-chip 50. In one embodiment, if a malfunction occurs during operation, the device records items such as an error code, device settings, and sensor readings on the m-chip. Thus, when the m-chip 50 is presented to the manufacturer or its agent, the information is read to diagnose the malfunction.

[0053] In one embodiment, a specially programmed m-chip 50 contains data for updating settings, parameters, or other information on the instrument. In such an embodiment, once the m-chip 50 is read, the data on the instrument will be updated with new values ​​for subsequent use with a standard microfluidic cartridge.

[0054] In one embodiment, the device may adapt its operation based on information read from the m-chip 50. Different recipes or settings present on the m-chip 50 may require different interfaces, options, parameters, indicators, etc., to be presented to the operator. In a further embodiment, the chip may generate steps for the operator to follow (e.g., how much volume to load onto the chip) and include data to guide the operator through the steps of the recipe when the operator taps the chip on the device, or data used for that purpose.

[0055] In some embodiments, the reader 110 is a bidirectional wireless transceiver whose position within the device is shown as 110 in Figure 1. Its function is to work with the tag 20 to evaluate whether the positioning of the m-chip 50 is correct, the m-chip usage, and finally the m-chip programming. The reader 110 can write to and read from the data transmission sensor 20.

[0056] For example, when the device is switched on (the power switch at the rear of the machine), and when the m-chip 50 is inserted into the chip entry 82 along the platform 115, the pressure sensor on the platform 115 sends a signal to the cartridge switch 67, instructing the reader 110 to use the built-in antenna to transmit a signal to the tag 110.

[0057] The correct placement and orientation of the m-chip 50 is primarily guided by a pressure sensor, and then by the interaction of the tag 20 with the reader 110 for fine-tuning, which depends on a specific range of the data signal range 80, as shown in Figures 4A to 4C as areas enclosed by dashed lines. The signal range 80 is selected according to the shape and profile of the m-chip and how the m-chip interacts with the instrument to be positioned and identified. Depending on the size of the mixed instrument 100, the readable range 80 is 0 to 50 mm, or 0 to 20 mm, or 0 to 5 mm.

[0058] Tag 20 responds to the reader 110 with information written to the memory of tag 20. The logic patterns embodied in the m-chip and device of the present invention, and their interactions, are shown in the form of a flowchart in Figure 3. The reader 110 transmits the reading result to the microcontroller 300 in the device 100. The microcontroller 300 communicates with the main PCB 340 via the ribbon cable connector 68, and the main PCB 340 responds by causing the GUI 90 to transmit a pre-recorded image such as the following example:

[0059] "Cartridge detected! Neuro9(registered trademark)siRNA" Total volume: 248 μL Press the button below to start the preparation. If the m-chip is not detected on platform 115: "Please insert the following new cartridge." Alternatively, if the m-chip is detected on platform 115 but not properly positioned: "No cartridge found. Please insert a cartridge below." The user can select a mode from the menu screen. "Mode: Kit formulation auto-purge" If the m-chip is not of the correct type for the mode selected by the user on GUI90, "The cartridge is incorrect. This cartridge is for kit mode." or "The cartridge is incorrect. This cartridge is for formulation mode." If the m-chip is already in use "The cartridge has already been used!"

[0060] The exact wording can be updated with each chip manufacturing. Note that this represents a significant advance over the use of prior art equipment and microfluidic chips, for which information regarding the success or failure of the chip and its formulation was not available to the user.

[0061] Figure 7 illustrates four different screenshots from the graphical user interface 90 showing what information is read from the m-chip 50. In this example, a prototype NanoAssemblr® Spark® small-volume mixer instrument (Precision NanoSystems Inc., Vancouver, BC) displays a menu screen, which then displays one of two different screens depending on which mode of m-chip is inserted. In the formulation mode on the left, the user is prompted to enter their formulation volume. In mode 2, the parameters are not variable and the operator is simply prompted to start a given recipe procedure, so on the right, the GUI simply indicates that the chip has been detected and prompts the user to press the start button 87 when ready (see Figure 1 for the overall diagram). The bottom screen displays "Done" and prompts the user to remove the m-chip and use the formulation.

[0062] The device 100 selects appropriate information to display on its GUI 90 based on the data from the data transmission sensor 20.

[0063] Therefore, this disclosure relates to a disposable cartridge comprising an m-chip 50 for storing data and an embedded data-transmitting component such as an RFID tag 20. By using this cartridge together with accompanying scientific instruments that are considered a system, information can be transferred bidirectionally (read from the m-chip 50 to the instrument at the tag 20, or written to the m-chip 50 by the instrument), particularly facilitating ease of use, software updates, troubleshooting, and end-user licensing. Various embodiments, used individually or in combination to form further embodiments, are described below.

[0064] Example 1: Manufacturing of M-chips RFID 20 is used as a means of storing and reading data on the m-chip 50. In one such example, an RFID reader 110 was embedded inside a NanoAssembrl® Spark® laboratory research instrument 100. In this particular case, a DLP-RFID2 (DLP Design, Allen, Texas) reader (#+1) was mounted on the underside of the instrument's microfluidic cartridge storage tray 115. This reader successfully read a 7.5 mm RFID tag placed on the Spark® m-chip 50 (meeting ISO / IEC 15693 (Verigenics, Southampton, Pennsylvania) specification) when it was correctly inserted and positioned inside the Spark. The RFID reader 110 was directly connected to the instrument's internal microcontroller (#+2) to communicate using industry-standard protocols.

[0065] During the manufacturing of the m-chip 50, the RF chip 20 was attached to the recess 25 on the underside of the front m-chip 50 using a double-sided adhesive film. The RFID 20 was programmed using standard techniques for programming such tags (the method may differ, but the vendor provides standard instruction manuals or software). In this example, a simple handheld programming device was used to program the tag.

[0066] Example 2: Identifying information of the data transmission sensor memory block The m-chip 50 was programmed to execute a specific set of parameters required to formulate 2 nanomoles of siRNA into lipid nanoparticles for delivery to neurons in vitro.

[0067] The data to be stored in the RFID tags was loaded into the host computer in the form of a .csv file. The host computer divided this data into 8-byte blocks, which were to be written to the RFID tags one at a time. The host computer sent a Write Block command along with one block of data to the RFID reader / writer module via an RS-232 serial connection. The RFID reader / writer module generated an electromagnetic field to power and communicate with the RFID tags, in accordance with the ISO-15693 standard.

[0068] The module sent a Write Block command. If the RFID tag is within range of the module's antenna, the tag saves the data block to its non-volatile internal memory and responds to the RFID module with a success code. The RFID module waits for the tag's response and then reports to the host computer whether the write was successful.

[0069] Steps 4-7 were repeated until all data had been transmitted to and stored in the RFID tag.

[0070] The pass / fail scenario programmed into the chip simply presented the following error code: ST01: No chip inserted. ST02: Used chip inserted. ST03: The wrong chip is being used for the current mode. This is a kit chip for formulation mode. ST04: The wrong chip is being used for the current mode. This is a formulation chip for kit mode. ST05: Chip inserted during purging. ST06: Chip cannot be read. RFID header is missing. ST07: Chip cannot be read. Incorrect checksum.

[0071] Example 3: Nucleic acid formulation

[0072] To formulate using the Spark® mixing instrument, the operator used an m-chip as shown in Figure 2A. Formulation buffer was dispensed as an aqueous solution into the exit well, siRNA (Integrated DNA Technologies, Coralville, Iowa) (Neuro9 Spark Kit®, Precision NanoSystems Inc., Vancouver, British Columbia) into one well of the m-chip's inlet, and a lipid nanoparticle solution in ethanol (see Ramsay et al. above) into the second inlet. The manifold and cover were placed on the m-chip, and the covered m-chip was then inserted into the Spark® micromixer. After insertion, the instrument read the RFID tag information to confirm compatibility and unused status, and the instrument screen displayed confirmation to the operator of the type of formulation programmed into the m-chip, instructing them to press "Start" when ready to proceed.

[0073] The device then executed the formulation according to the parameters stored in the RFID tag. After the formulation process was successfully completed, the data on the tag was updated by a Spark® reader to indicate that an m-chip had been used.

[0074] After formulation, the operator removed the m-tip from the instrument, removed the cap and manifold, and pipetted the resulting formulation from the exit well. The m-tip 50 (along with the corresponding tag) was then disposed of in accordance with local regulations.

[0075] Example 4: Programming an advanced smart M-chip

[0076] The m-chip is prepared in the same manner as in Examples 1 and 2, but the error codes include the following: ST08: Flow error ST09: Pressure Error

[0077] If an error occurs during the formulation process, such as pressure loss, the corresponding error code or message will be displayed to the operator and written to the RFID tag.

[0078] Enhanced feedback from the device to the tag, and vice versa, includes pressure loss, unexpected resistance, or unexpected lack of resistance. This enhanced data is included in GUI readouts that notify the user of further exceptions. These exceptions help diagnose mechanical problems with the device and aid in device repair.

[0079] Although specific embodiments of the present invention have been described and illustrated, such embodiments are merely illustrative and should not be considered to limit the invention to the extent that it is interpreted in accordance with the claims.

[0080] The present invention may further include the following embodiments. [Section 1] A mixing apparatus comprising a motor, pump, microfluidic chip engagement tray with integrated data transmitter / receiver, microcontroller, and user interface. [Section 2] The apparatus described in item 1, wherein the data transmitter / receiver includes an RFID reader. [Section 3] The apparatus according to item 1, wherein the transmitter / receiver detects the correct positioning of the microfluidic chip on the engagement tray. [Section 4] The apparatus described in Section 1 for use in conjunction with a microfluidic chip containing data components. [Section 5] The apparatus according to any one of claims 1 to 4, wherein the microfluidic chip is engaged with the apparatus and the apparatus and the microfluidic chip communicate with each other when the apparatus is powered on. [Section 6] A programmable microfluidic chip including inlet, microchannel, outlet, and data components. [Section 7] The microfluidic chip according to item 6, wherein the data component is a radio frequency identification tag ("RFID"). [Section 8] The microfluidic chip according to item 7, wherein the RFID has a defined readable range. [Section 9] The microfluidic chip according to item 7 or 8, wherein the RFID has a defined readable range of 0 to 5 mm. [Section 10] The microfluidic chip according to item 7 or 8, wherein the RFID has a defined readable range of 0 to 20 mm. [Section 11] The microfluidic chip according to item 7 or 8, wherein the RFID has a defined readable range of 0 to 50 mm. [Section 12] The microfluidic chip according to any one of claims 6 to 11, wherein the microfluidic chip includes a manifold and cover to which are detachably attached. [Section 13] The data component is a microfluidic chip according to any one of claims 6 to 12, wherein the data component is readable by the instrument and contains stored data that instructs the operation of the instrument. [Section 14] The microfluidic chip according to item 13, wherein the stored data includes a state indicator containing the history data of the microfluidic chip. [Section 15] The stored data includes the type or purpose of the microfluidic chip as described in item 13. [Section 16] The data component is read by the device described in item 1, processed by a microcontroller within the device, and the corresponding message is transmitted to the user interface on the device. A microfluidic chip as described in item 6, which communicates with the user via a face. [Section 17] The microfluidic chip according to paragraph 16, wherein the data read from the data component determines what information the device transmits to the user interface. [Section 18] The microfluidic chip according to paragraph 15, wherein the data read from the data component includes information transmitted to the user interface and presented to the user as a set of instructions. [Section 19] The microfluidic chip according to paragraph 15, wherein the data read from the data component is transmitted to the user interface described above and includes information presented to the user as a set of options. [Section 20] The microfluidic chip according to any one of claims 6 to 19, wherein the data component can receive, store, and transmit data. [Section 21] A system for formulating therapeutic drugs for research use, comprising a device having a pump, a microfluidic chip engagement tray incorporating a data transmitter / receiver, a microcontroller, a memory storage device, and a graphic display, and a replaceable microfluidic chip, wherein the therapeutic drug is selected from the group consisting of nucleic acids, peptides, proteins, and hydrophobic small molecules.

Claims

[Claim 1] A mixing apparatus comprising a motor, pump, microfluidic chip engagement tray incorporating a data transmitter / receiver, a microcontroller, and a user interface.

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