Multi-well test plates, also called micro-titer plates or simply titer plates, are used for assays involving biological or biochemical materials. A titer plate is a plate-shaped structure that includes multiple reaction chambers. The reaction chambers, also called cavities, cups, or wells, are arranged in rows and columns to form a multi-cellular or honeycomb structure. A small amount of a liquid sample is placed in each reaction chamber. During testing, a reaction (e.g., a chemical or biological reaction) takes place, which may be accompanied by a coloration or discoloration of the liquid samples. The color change resulting from the reaction may be monitored optically or electro-optically.
In one example, a modular titer plate assembly includes a multi-well plate, a sensor assembly, and a mainboard. The multi-well plate includes a two-dimensional array of wells. The sensor assembly is detachably mounted to the multi-well plate. The sensor assembly includes a two-dimensional array of sensors aligned with the two-dimensional array of wells. The mainboard is detachably mounted to the sensor assembly.
In another example, a modular titer plate assembly includes a multi-well plate. The multi-well plate includes a two-dimensional array of wells. The two-dimensional array of wells includes a row of wells and includes channels. Each channel couples between respective adjacent wells of the row of wells. Each channel is configured to allow liquid to flow between the adjacent wells.
In a further example, a system includes a modular titer plate assembly and a data processor. The modular titer plate assembly includes a multi-well plate, a sensor assembly, and a mainboard. The multi-well plate includes a two-dimensional array of wells. The sensor assembly is detachably mounted to the multi-well plate. The sensor assembly includes a two-dimensional array of sensors aligned with the two-dimensional array of wells. The two-dimensional array of sensors includes at least one of: a pH sensor, a conductivity sensor, an oxygen sensor, or a temperature sensor. The mainboard is detachably mounted to the sensor assembly. The data processor is communicatively coupled to the modular titer plate assembly.
Electro-chemical analysis capabilities can be added to a titer plate by adding electrodes and/or sensing electronics to the wells of the titer plate. However, titer plates are generally discarded after use, so adding sensing and readout/communication electronics to each well of a titer plate (e.g., 24, 48, 96 or more wells) can substantially increase the cost of titer plate replacement. In some titer plate applications, sensing of a parameter (e.g., pH) may be implemented using a reference electrode. Discrete reference electrodes are costly, and inclusion of a reference electrode per well substantially increases cost. Some systems employ a titer plate robot that sequentially applies a reference electrode to each well, thereby reducing electrode cost. However, moving the reference electrode from well to well increases the risk of contamination.
The modular titer plate assembly described herein includes sensing electronics to provide “lab-on-chip” functionality, and reduces the costs associated with titer plate replacement and use of per-well reference electrodes. The modular title plate assembly includes a multi-well plate, a sensor assembly, and a mainboard. The sensor assembly is detachably mounted to the multi-well plate, and includes sensor electronics for each well of the multi-well plate. The mainboard is detachably mounted to the sensor assembly, and includes communication and/or processing electronics coupled to the sensor electronics of the sensor assembly. The replacement cost of the modular titer plate is reduced by allowing for reuse of the sensor assembly and the mainboard while the multi-well plate may be replaced or cleaned. Also, the detachability of the mainboard and the sensor assembly from the multi-well plate can also facilitate testing, diagnostics, cleaning of the multi-well plate, and maintenance of the sensor electronics of the sensor assembly and of the communication and processing electronics of the mainboard.
The modular titer plate assembly described herein can also facilitate electro-chemical analysis. Specifically, the modular titer plate assembly includes channels between adjacent wells. Each channel can form a salt bridge between the respective wells. The salt bridge can support differential sensing, which can eliminate the need of reference electrodes.
The sensor assembly 104 includes electronic sensors (e.g., a sensor integrated circuit) coupled to the bottom of each well 110. The electronic sensors may include a pH sensor (e.g., an ion sensitive field effect transistor), a conductivity sensor, an oxygen sensor, a temperature sensor, and/or other sensors measuring a parameter of a liquid contained within the well.
The mainboard 106 is detachably mounted to the sensor assembly 104, and includes communication circuitry that is coupled to the electronic sensors of the sensor assembly 104. The communication circuitry receives measurement signals from the electronic sensors of the sensor assembly 104, and transfers the measurement signals to a computing device external to the modular titer plate assembly 100. Various examples communication circuitry may be provided in examples of the modular titer plate assembly 100. For example, the communication circuitry may include a microcontroller coupled to each of the electronic sensors of the sensor assembly 104, where the microcontroller processes the measurement signals received from the electronic sensors, and transmits the measurement signals to the external computing device via a digital communication interface (e.g., universal serial bus (USB)). In another example, the communication circuitry includes a switch network that selectively connects each of the electronic sensors to the external computing device. The switch network may include relays or semiconductor switches.
Each row 112 includes a channel 202 coupled between adjacent wells 110. The channel 202 may provide a salt bridge between the adjacent wells 110. For example, the channel 202 may receive an electrolyte (e.g., potassium chloride, potassium nitrate, sodium chloride, etc.) via a paper, fiber, gel, or other medium. The salt bridge prevents the flow of liquid between the adjacent wells 110, and allows diffusive ion flow between the adjacent wells 110, creating an electrical connection between the electrochemical cells in the adjacent wells 110. The channel 202 includes a plug port 204. The plug port 204 allows a plug (e.g., a rubber tube) to be inserted in the channel 202. The plug blocks movement of liquid between the adjacent wells 110 when no salt bridge exists to electrically isolate between the adjacent wells 110, and to block liquid from flowing between the adjacent wells 110.
The multi-well plate 102 may also include passages 206 for passing a retainer, such as a bolt or a screw, through the multi-well plate 102 to the sensor assembly 104. The retainer fastens the multi-well plate 102 to the sensor assembly 104, and aligns the wells 110 of the multi-well plate 102 with the electronic sensors of the sensor assembly 104. Some examples of the multi-well plate 102 may lack the passages 206. In those examples, the multi-well plate 102 may include magnets or other fasteners (not shown in the figures) to align and couple with the sensor assembly 104.
An opening 406 in the printed circuit board 404 allows the well 110 to interface with the sensor integrated circuit 405 mounted on the bottom-side of the printed circuit board 404. The base 402 includes mounting holes 410 configured to receive bolts or screws that align the electronic sensors of the sensor assembly 104 with the wells of the multi-well plate 102, and to mount the sensor assembly 104 to the multi-well plate 102. The bolts or screws can also be removed from the mounting holes 410 to detach the sensor assembly 104 from the multi-well plate 102. The sensor assembly 104 also includes pins or contacts (e.g., spring-loaded pogo-pins) that provide electrical connections between the electronic sensors 403 and the mainboard 106.
The mainboard 106 includes sets of contacts 408. The sets of contacts 408 engage pins (e.g., spring-loaded pins) of the sensor assembly 104 to provide electrical connections between the mainboard 106 and the sensor assembly 104 for transmission of signals and power. In some examples of the mainboard 106, the sets of contacts 408 are arranged in a two-dimensional array, with a set of the contacts 408 coupled to a respective electronic sensor 403 of the sensor assembly 104.
The mainboard 106 may include microcontrollers or switching circuits associated with contacts 408. For example, a microcontroller or switching circuit may be coupled to each set of the contacts 408. Some examples of the mainboard 106 include mounting holes 412 configured to receive bolts or screws that pass through the multi-well plate 102 and the sensor assembly 104 to mount the mainboard 106 to the sensor assembly 104 and the multi-well plate 102. The mainboard 106 may also be aligned with the sensor assembly 104 by the bolts or screws. In some examples, the mounting hole 412 may include a threaded socket configured to engage a screw to fasten/mount the mainboard 106 to the sensor assembly 104. Some examples of the mainboard 106 may also include two or more pins 416, each pin 416 configured to engage a respective socket of the sensor assembly 104 to facilitate alignment between the sensor assembly 104 and the mainboard 106.
In this description, the term “couple” may cover connections, communications, or signal paths that enable a functional relationship consistent with this description. For example, if device A generates a signal to control device B to perform an action: (a) in a first example, device A is coupled to device B by direct connection; or (b) in a second example, device A is coupled to device B through intervening component C if intervening component C does not alter the functional relationship between device A and device B, such that device B is controlled by device A via the control signal generated by device A.
Also, in this description, the recitation “based on” means “based at least in part on.” Therefore, if X is based on Y, then X may be a function of Y and any number of other factors.
A device that is “configured to” perform a task or function may be configured (e.g., programmed and/or hardwired) at a time of manufacturing by a manufacturer to perform the function and/or may be configurable (or reconfigurable) by a user after manufacturing to perform the function and/or other additional or alternative functions. The configuring may be through firmware and/or software programming of the device, through a construction and/or layout of hardware components and interconnections of the device, or a combination thereof.
As used herein, the terms “terminal”, “node”, “interconnection”, “pin” and “lead” are used interchangeably. Unless specifically stated to the contrary, these terms are generally used to mean an interconnection between or a terminus of a device element, a circuit element, an integrated circuit, a device or other electronics or semiconductor component.
A circuit or device that is described herein as including certain components may instead be adapted to be coupled to those components to form the described circuitry or device. For example, a structure described as including one or more semiconductor elements (such as transistors), one or more passive elements (such as resistors, capacitors, and/or inductors), and/or one or more sources (such as voltage and/or current sources) may instead include only the semiconductor elements within a single physical device (e.g., a semiconductor die and/or integrated circuit (IC) package) and may be adapted to be coupled to at least some of the passive elements and/or the sources to form the described structure either at a time of manufacture or after a time of manufacture, for example, by an end-user and/or a third-party.
While certain elements of the described examples are included in an integrated circuit and other elements are external to the integrated circuit, in other example embodiments, additional or fewer features may be incorporated into the integrated circuit. In addition, some or all of the features illustrated as being external to the integrated circuit may be included in the integrated circuit and/or some features illustrated as being internal to the integrated circuit may be incorporated outside of the integrated. As used herein, the term “integrated circuit” means one or more circuits that are: (i) incorporated in/over a semiconductor substrate; (ii) incorporated in a single semiconductor package; (iii) incorporated into the same module; and/or (iv) incorporated in/on the same printed circuit board.
Uses of the phrase “ground voltage potential” and/or “ground” in this description include a chassis ground, an Earth ground, a floating ground, a virtual ground, a digital ground, a common ground, and/or any other form of ground connection applicable to, or suitable for, the teachings of this description. In this description, unless otherwise stated, “about,” “approximately” or “substantially” preceding a parameter means being within +/−10 percent of that parameter, or, if the value is zero, a reasonable range of values around zero.
Modifications are possible in the described embodiments, and other embodiments are possible, within the scope of the claims.
This application claims priority to U.S. Provisional Application No. 63/289,661, filed Dec. 15, 2021, entitled “Modular Differential Lab-on-Chip Titer Plate,” the entirety of which is hereby incorporated by reference.
Number | Date | Country | |
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63289661 | Dec 2021 | US |