Systems and methods for analyzing microvolume samples
Patent Information
- Application Number
- CN202610232828.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2025-02-27
- Filing Date
- 2026-02-27
- Publication Date
- 2026-08-28
AI Technical Summary
尽管已经开发了各种不同类型的微体积分析设备来进行这种评估,但在改进微体积分析设备的使用和/或设计以有助于液体样品的一种或多种性质的分析方面仍有空间
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Figure CN122651840A_ABST
Abstract
Description
Technical Field
[0001] This disclosure relates in its entirety to systems and methods for analyzing liquid samples, and more specifically to systems and methods for determining the temperature of micro-volume liquid samples using electrochemical measurements. Background of the Invention Microvolume analysis devices are important tools in clinical and research applications, facilitating the analysis of one or more properties of liquid samples. These devices allow for the rapid and easy understanding of various properties of liquid samples, such as quantity and / or purity. For example, microvolume analysis devices can be configured to perform quantitative assessments of nucleic acids and proteins in liquid samples. Although various types of microvolume analysis devices have been developed for this assessment, there is still room for improvement in the use and / or design of microvolume analysis devices to facilitate the analysis of one or more properties of liquid samples. Summary of the Invention
[0002] An example system for analyzing a sample includes: a first surface including at least a portion of a first electrode; a second surface including at least a portion of a second electrode, the second surface being positioned relative to the first surface for holding the sample between the first surface and the second surface by surface tension; and an electronic processing unit configured to: apply at least one electrical signal to both ends of the sample via the first electrode and the second electrode; determine a first conductivity of the sample at a first frequency associated with the at least one electrical signal and a second conductivity of the sample at a second frequency associated with the at least one electrical signal based on the at least one electrical signal applied to both ends of the sample; and determine a temperature of the sample based on the first conductivity and the second conductivity.
[0003] An example computer program product is contained in a non-transitory computer-readable storage medium and includes computer instructions for performing a process. The process includes determining that a sample is positioned between a first surface and a second surface, wherein the sample is held between the first surface and the second surface by surface tension; applying at least one electrical signal to both ends of the sample via a first electrode associated with the first surface and a second electrode associated with the second surface; determining a first conductivity of the sample at a first frequency associated with the at least one electrical signal and a second conductivity of the sample at a second frequency associated with the at least one electrical signal, based on the at least one electrical signal applied to both ends of the sample; and determining a temperature of the sample based on the first conductivity and the second conductivity.
[0004] An example method for measuring the electrochemical properties of a sample includes: providing a sample positioned between a first surface and a second surface of a sample analysis system, wherein the sample is held between the first surface and the second surface by surface tension; applying at least one electrical signal to both ends of the sample by the sample analysis system via a first electrode associated with the first surface and a second electrode associated with the second surface; determining, based on the at least one electrical signal applied to both ends of the sample, a first conductivity of the sample at a first frequency associated with the at least one electrical signal and a second conductivity of the sample at a second frequency associated with the at least one electrical signal; determining, by the sample analysis system, a temperature of the sample based on the first conductivity and the second conductivity; determining the electrochemical properties of the sample by the sample analysis system; and generating, by the sample analysis system, a value representing the electrochemical properties of the sample at a baseline temperature based on the determined electrochemical properties of the sample and the determined temperature.
[0005] It should be understood that the above overview is provided to present, in a simplified form, some concepts that are further described in the detailed description. It is not intended to identify key or essential features of the claimed subject matter, the scope of which is solely defined by the claims following the detailed description. Attached Figure Description
[0006] The accompanying drawings illustrate various specific embodiments and are part of the specification. The specific embodiments shown are merely examples and do not limit the scope of this disclosure. Throughout the drawings, the same or similar reference numerals denote the same or similar elements.
[0007] Figure 1 An example sample analysis system that can be implemented based on the principles described herein is illustrated.
[0008] Figure 2A Examples are given based on the principles described in this article. Figure 1 An example liquid analysis system implemented using a sample analysis system.
[0009] Figure 2B Examples are given of principles that can be included in this document. Figure 2A Example block diagram of a controller in a liquid analysis system.
[0010] Figure 3 Examples are given based on the principles described in this article. Figure 1 Another example of a liquid analysis system is the implementation of a sample analysis system that includes a visible light emitting device.
[0011] Figure 4 Example circuit diagrams are shown that can be implemented based on the principles described in this article.
[0012] Figure 5A and Figure 5B An example voltage trace that can be implemented based on the principles described herein is illustrated.
[0013] Figure 6A An example cycle of a voltage trace that can be implemented according to the principles described herein is illustrated.
[0014] Figure 6B and Figure 6C Examples are given based on the principles described in this article. Figure 6A Example Fourier decomposition components of the voltage trace shown.
[0015] Figure 7 Example graphs depicting the conductivity of different solutions at different frequencies and two temperatures are shown, based on the principles described herein.
[0016] Figure 8 Example graphs illustrating conductivity difference analysis that can be performed according to the principles described herein are presented.
[0017] Figure 9 Example graphs depicting the conductivity of different solutions at different frequencies and three temperatures are shown, based on the principles described herein.
[0018] Figure 10 Example flowcharts are shown, including operations that can be performed according to the principles described herein.
[0019] Figure 11 An example graphical user interface (GUI) view that can be displayed during the measurement process according to the principles described herein is illustrated.
[0020] Figure 12 An example method for analyzing micro-volume samples based on the principles described herein is illustrated.
[0021] Figure 13 An example computing device based on the principles described herein is illustrated. Detailed Implementation
[0022] Samples in drug research (such as purified proteins and DNA) are often produced in small quantities after time-consuming and expensive procedures. Careful control of the ion concentration and pH of the buffers used to preserve these samples is necessary to prevent sample degradation and ensure the success of downstream processes such as PCR and gel electrophoresis. The concentration of the sample can be determined based on UV-VIS absorbance measurements. Spectrophotometers designed for use with optical fibers enable the measurement of the optical properties of micro-volume samples, such as samples ranging from 0.25 μL to 10 μL. Such spectrophotometers use the surface tension of the liquid sample to confine the sample during optical analysis. Examples of spectrophotometers are disclosed in U.S. Patents US6809826B2 and US6628382B2, the entire contents of which are incorporated herein by reference. Patent application WO2024173752A1 further discloses methods and systems for measuring the electrochemical properties of micro-volume samples, the entire contents of which are incorporated herein by reference.
[0023] The applicant recognizes that measurements of the electrochemical properties of the sample (such as pH or conductivity) vary with sample temperature. Therefore, accurate temperature measurements are necessary to interpret the results of the electrochemical property measurements.
[0024] This document describes systems and methods for analyzing microvolume samples. As will be described in more detail below, an exemplary system for analyzing a sample includes: a first surface including at least a portion of a first electrode; a second surface including at least a portion of a second electrode, the second surface being positioned relative to the first surface for holding the sample between the first and second surfaces by surface tension; and an electronic processing unit configured to: apply at least one electrical signal across the sample via the first and second electrodes; determine a first conductivity of the sample at a first frequency associated with the at least one electrical signal and a second conductivity of the sample at a second frequency associated with the at least one electrical signal based on the at least one electrical signal applied across the sample; and determine a temperature of the sample based on the first and second conductivity.
[0025] Therefore, the temperature of a micro-volume sample can be determined based on conductivity measurements at two different frequencies. The sample temperature can be determined simultaneously and / or immediately following optical and / or electrochemical measurements of the same micro-volume sample, without the need for a physical temperature sensor.
[0026] The systems and methods described herein are associated with a variety of advantages and benefits. For example, systems and methods such as those described herein facilitate the determination of the temperature of microvolume samples in conjunction with or in parallel with other properties such as pH and conductivity. Doing so reports the electrochemical properties of the sample as if the sample were measured at a standard (or baseline) temperature of 25 °C. Additionally, systems and methods such as those described herein facilitate the measurement of sample temperature without modification to the sample analysis equipment (e.g., without the need to add a dedicated temperature sensor and / or without obstructing the light path or other components). Furthermore, systems and methods such as those described herein can determine sample temperature automatically without user input. These and other benefits that the systems and methods described herein can achieve will become apparent from the following disclosure.
[0027] The system and method described herein utilize the fact that the measured conductivity of many samples varies not only with temperature but also with the frequency of the electrical signal applied to the sample. Therefore, to determine the temperature of a sample, the system can analyze conductivity measurements at multiple different frequencies of the electrical signal applied to both ends of the sample. For this purpose, the system can apply electrical signals to both ends of the sample via a first electrode and a second electrode. The system can apply the electrical signals to the electrode ends in any suitable manner. For example, applying the electrical signals may include applying an AC signal to both ends of the sample. The AC signal can have any form, voltage value, and / or oscillation frequency suitable for a particular specific implementation. For example, in some specific implementations, the AC signal may be a 20 kHz AC square wave with a 0 V bias and a 6 V peak-to-peak voltage.
[0028] Based on the at least one electrical signal applied to both ends of the sample, the system can determine a first conductivity of the sample at a first frequency associated with the at least one electrical signal and a second conductivity of the sample at a second frequency associated with the at least one electrical signal. This can be achieved by any suitable means. In some specific embodiments, the system can simultaneously determine the first and second conductivity by applying an electrical signal comprising multiple frequency components. That is, the first and second conductivity can be determined based on a single electrical signal applied to both ends of the sample. The single electrical signal may include multiple frequency components, and the first and second frequencies are two of these multiple frequency components. A frequency component refers to a unique sinusoidal frequency element present in an electrical signal applied to or measured from the sample, including a fundamental frequency and one or more harmonic frequencies, which can be identified by frequency domain analysis of the signal. In one example, the second frequency is a harmonic of the first frequency. Alternatively, the system 100 can determine the first conductivity based on the first electrical signal at a first time and determine the second conductivity based on the second electrical signal at a second time after the first time.
[0029] In one example, the second frequency is higher than the first frequency. The second frequency is greater than 50 kHz, and the first frequency is not greater than 50 kHz. The difference between the first and second frequencies can exceed 20 kHz. In another example, the higher second frequency is not less than 60 kHz, and the difference between the first and second frequencies is not less than 30 kHz or 40 kHz. By setting the second frequency to a higher frequency, the second conductivity measurement is less sensitive to frequency (i.e., the rate of change of conductivity with frequency is smaller). Therefore, the second conductivity can be directly used to determine the conductivity of the sample at a given temperature. By increasing the difference between the first and second frequencies, the temperature of the sample can be estimated with greater accuracy.
[0030] Figure 1 An example sample analysis system 100 (“System 100”) that can be implemented according to the principles described herein is illustrated. As shown, System 100 may include (but is not limited to) an electronic processing unit 102 communicatively coupled to a sample analysis apparatus 104. System 100 may be implemented in any suitable manner. For example, as shown, the electronic processing unit 102 and the sample analysis apparatus 104 may be implemented by separate devices communicatively coupled to each other via any suitable wired and / or wireless communication protocol. In some alternative embodiments, the electronic processing unit 102 may be included within the sample analysis apparatus 104. An exemplary embodiment of System 100 is described herein.
[0031] The electronic processing unit 102 may be implemented by one or more computing devices with processing capabilities, such as one or more desktop computers, controllers, mobile devices (e.g., smartphones, tablets), etc. As shown, the electronic processing unit 102 includes a memory 106 and a processor 108 that are selectively and communicatively coupled to each other. The memory 106 and the processor 108 may each include or be implemented with hardware and / or software components (e.g., processor, memory, communication interface, instructions stored in memory for execution by the processor, etc.).
[0032] Memory 106 may maintain (e.g., store) executable data that processor 108 uses to perform any of the operations described herein. For example, memory 106 may store instruction 110, which can be executed by processor 108 to perform any of the operations described herein. Instruction 110 may be implemented by any suitable application, software, code, and / or other instance of executable data.
[0033] The memory 106 may also maintain any data received, generated, managed, used, and / or transmitted by the processor 108. The memory 106 may store any other suitable data appropriate for a particular implementation. For example, the memory 106 may store measurement data (e.g., pH data, optical property data, sample concentration data, sample volume data, conductivity data, temperature data, etc.), image data, calibration data, user interface content, and / or any other suitable data.
[0034] Processor 108 may be configured to perform (e.g., execute instructions 110 stored in memory 106 to perform) various processing operations associated with the analysis of microvolume samples using components of sample analysis device 104. For example, processor 108 may perform one or more operations described herein to automatically determine the temperature of a sample based on multiple conductivity measurements. As used herein, the expression “automatically” means performing an operation (e.g., the operation of analyzing a sample) or a series of operations without further user input. For example, loading a sample into sample analysis device 104 may trigger the automatic determination of one or more properties of the sample without further input from that user or any other user. These and other operations that processor 108 may perform are described herein.
[0035] Processor 108 may be configured to execute computer programs to perform any of the operations described herein. The computer programs may be written in any programming language, including compiled and / or interpreted languages, and may be deployed in any form, including as standalone programs or as modules, components, subroutines, or other units suitable for use in a computing environment. The computing programs may be deployed to be executed by processor 108 located at a single site, or distributed across multiple sites and interconnected via a network.
[0036] The sample analysis apparatus 104 can be implemented by any suitable device, apparatus, or system having components that can be used to analyze one or more micro-volume samples. For example, the sample analysis apparatus 104 can be implemented by a spectrophotometer. Examples of spectrophotometers are disclosed in U.S. Patents US6,809,826B2 and US6,628,382B2, the entire contents of which are incorporated herein by reference.
[0037] The sample analysis apparatus 104 can use the confinement effect of surface tension on the sample to measure one or more properties of a liquid sample. The liquid sample may have a volume of, for example, 0.25 μL to 10 μL, or any other suitable volume. These properties may include physical, electrochemical, and / or optical properties, such as sample volume, temperature, conductivity, pH level, optical density, absorbance, transmittance, fluorescence, etc.
[0038] In some examples, when a sample is provided in sample analysis device 104, system 100 can measure multiple different properties simultaneously or sequentially. For example, system 100 can sequentially measure a first property of the sample (e.g., optical property), then a second property (e.g., a first electrochemical property, such as pH level), then a third property (e.g., a second electrochemical property, such as conductivity), and then a fourth property (e.g., temperature of the sample).
[0039] Figure 2A A liquid analysis system 200 (“System 200”) is illustrated, wherein System 100 may be implemented in some examples. For example... Figure 2A As shown, the liquid analysis system 200 includes bases 202 and 204, a sample-facing surface 206 of base 202 and a sample-facing surface 208 of base 204 (configured to hold a sample 210 of microvolume liquid), a controller 212, electrical connections (e.g., wires) 214 and 216, a camera 218, actuators 220 (e.g., one or more stepper motors and one or more associated lead screws), and an electronic processing unit 222. Figure 2A The various components shown can be similar to and / or implemented. Figure 1 The components shown. For example, electronic processing unit 222 may be a specific implementation of electronic processing unit 102, and Figure 2A The various other components shown may be a specific implementation of sample analysis apparatus 104. System 200 can be used to measure one or more properties of sample 210 via one or more of the methods described herein. System 200 can be vertically positioned such that the first and second surfaces are horizontal (in the XY plane).
[0040] In some specific implementations, Figure 2A The components of the illustrated system 200 may be included in a common housing forming an instrument or device. However, in other embodiments, one or more components of system 200 may be contained in separate housings or devices and may be coupled as needed (e.g., communicative, electrical, mechanical, etc.) to perform the methods described herein. It should be understood that the functionality performed by the components of system 200 described herein can be combined and distributed in various ways. For example, in some embodiments, electronic processing unit 222 may be part of controller 212, wherein controller 212 is configured to perform the functionality of electronic processing unit 222 described herein. Furthermore, the functionality described herein to be performed by controller 212 may be distributed among multiple controllers 212. Liquid analysis system 200 may also include additional components (such as power supply components), user interface 224 (such as displays and / or user input devices), housing, etc.
[0041] Furthermore, in some specific implementations, although the sample-facing surfaces 206 and 208 are in Figure 2A The orientation is shown as horizontal (e.g., to establish the upper and lower surfaces), but it should be understood that other orientations are also possible, such as a vertical orientation, in which the sample-facing surfaces 206 and 208 establish the left and right surfaces. Therefore, although specific implementations may be described herein with regard to the upper and lower surfaces, the specific implementations described herein are equally applicable to systems including two surfaces in other orientations.
[0042] like Figure 2A As shown, sample 210 is loaded onto one of the sample-facing surfaces 206 or 208, such as sample-facing surface 206 of base 202, using a pipette. When sample 210 is emptied from the pipette, if the droplet has sufficient volume, it will spread to cover sample-facing surface 206 until it encounters the edge of sample-facing surface 206 or 208, such as the edge of sample-facing surface 206. Sample 210 is contained between sample-facing surface 206 of base 202 and sample-facing surface 208 of base 204 by surface tension. In some embodiments, 2 μL of aqueous solution can effectively cover an area of approximately 2 mm diameter on one or both of sample-facing surfaces 206 and 208. Alternatively, the spreading of sample 210 may be limited by variations in surface tension characteristics. For example, in some embodiments, a polymeric surface of the material can be used to limit the spreading of the solution.
[0043] Using one or more actuators 220 (such as one or more stepper motors), the base 202 is brought into the measurement position, and optionally subsequently into a position closely proximal to the base 204, contacting the deposited sample 210 and wetting the entire confining surface before returning to the sample measurement position. The actuator 220 shown herein is mechanically coupled to the lower base 204 for adjusting the sample-facing surface 208. It should be understood that the actuator 220 may be mechanically coupled to a cap engaged with the base 204. In some examples, the actuator 220 may instead be coupled to the base 202 and / or a cap engaged with the base 202. In some examples, each of the bases 202 and 204 may be coupled to an actuator.
[0044] In some examples, the sample-facing surfaces 206 and 208 may have approximately the same area. Alternatively, the sample-facing surfaces 206 and 208 may have different areas. For example, in some embodiments, the sample-facing surface 208 may be larger than the sample-facing surface 206 to provide a larger loading target. When two different sized surfaces are used and the smaller surface enters the sample compression position, the sample 210 can be drawn into the gap between the bases 202 and 204 by capillary action. In this configuration, the diameter of the smaller surface allows the sample to be centered between the sample-facing surfaces 206 and 208.
[0045] In some examples, the sample-facing surfaces 206 and 208 may be horizontally positioned flat surfaces for holding the sample 210. In other embodiments, one or both of the sample-facing surfaces 206 and 208 may have curved surfaces. Using curved surfaces can help position the sample 210 between the sample-facing surfaces 206 and 208, and in some embodiments, can help produce a consistent shape for the sample 210.
[0046] To measure the electrochemical properties (e.g., conductivity) of a liquid sample, the sample-facing surfaces 206 and 208 can be used as bipolar conductivity meters. Specifically, each of the sample-facing surfaces 206 and 208 may include at least a conductive portion. In some examples, the entire surface 206, the entire sample-facing surface 208, or both may be conductive. Such conductive portions 226 and 228 can be used as electrodes for transmitting and receiving electrical signals to and from the sample 210 in direct contact with the conductive portions. Here, such conductive portions 226 and 228 are also referred to as electrodes. The conductive portions 226 and 228 may be metallic surfaces with a diameter between 1 mm and 3 mm (e.g., 2.5 mm). One or both of the conductive portions 226 and 228 may be hydrophobic. For example, in some embodiments, one or both of the conductive portions 226 and 228 may be coated with a hydrophobic material coating, or the surfaces may be laser-treated to make them hydrophobic. In some examples, a portion of each of the sample-facing surfaces 206 and 208 may be electrically coupled to the electronic processing unit 222 via connections 214 and 216.
[0047] The spacing between the sample-facing surfaces 206 and 208 (and therefore the electrodes 226 and 228) can be controlled by vertically moving the position of one or more of the sample-facing surfaces 206 and 208 (e.g., via moving one or more of the bases 202 and 204). For example, the bottom base 204 can be moved by operating actuator 220.
[0048] The electronic processing unit 222 is configured to measure electrical signals via one or more of the electrodes 226 and 228 associated with the bases 202 and 204, and in some embodiments, is also configured to apply an oscillating (AC) voltage to the sample 210 via one or more of the electrodes 226 and 228.
[0049] For example, in some embodiments, the electronic processing unit 222 includes an electrical signal generator. The electronic processing unit 222 may include a circuit board for reading measured electrical signals (e.g., AC signals) from electrodes 226 and 228 (and optionally applying electrical signals via the electrodes), and software or firmware associated with the board may be configured to directly convert the voltage into electrochemical parameters (e.g., conductivity values) that can be transmitted to other components of the system 200. In other embodiments, instead of directly converting the voltage into one or more intermediate or filtered values, the electronic processing unit 222 may process the voltage into one or more intermediate or filtered values, which can be transmitted to the controller 212 for further processing, including, for example, determining the electrochemical properties of the sample 210. In some embodiments, the electronic processing unit 222 may include an electronic processor (e.g., a microprocessor) that can instruct the signal generator, process the measured electrical signals, or a combination thereof. For example, in order to measure the conductivity of sample 210, an electrical signal can be measured by one or more of electrodes 226 and 228 when an oscillating (AC) voltage is applied to the sample positioned between two flat metal surfaces via one or more of electrodes 226 and 228.
[0050] Camera 218 is positioned to capture one or more images of bases 202 and 204, such as at least a portion of sample-facing surfaces 206 and 208, and the intervals between these sample-facing surfaces 206 and 208, including any sample positioned between sample-facing surfaces 206 and 208. Images captured via camera 218 can be used to identify actuator positions (or stepper motor positions) relative to one or more intervals, sample volumes positioned between sample-facing surfaces 206 and 208, or combinations thereof. In some examples, liquid analysis system 200 may include a light source for illuminating sample 210 when images are captured via camera 218.
[0051] As described above, actuator 220 is configured to move at least one of the sample-facing surface 206 and the sample-facing surface 208 (i.e., at least one of the bases 202 and 204). Also as described above, in some embodiments, system 200 includes a plurality of actuators 220. In some embodiments, actuator 220 may include one or more stepper motors.
[0052] In some examples, system 200 may also include a cap (not shown) removably attachable to each of bases 202 and 204. For example, a first cap may be removably attached to base 202, and a second cap may be removably attached to base 204. Such caps may have a conductive material coating, which facilitates the detection of pH levels in sample 210. For example, the first cap may have a metal oxide coating (e.g., a ZnO coating), and the second cap may have a silver chloride (AgCl) coating.
[0053] The controller 212 is configured to communicate with the electronic processing unit 222 to receive measured electrical signals, and in some embodiments, to transmit commands to the electronic processing unit 222 to apply electrical signals via electrodes 226 and 228. The controller 212 is also configured to communicate with the camera 218 to transmit commands to the camera 218 to capture images and to receive the captured images. Furthermore... Figure 2A As shown, controller 212 is further configured to communicate with actuator 220 to send commands to actuator 220 and receive position information (e.g., motor steps) from actuator 220. Controller 212 may communicate with electronic processing unit 222, camera 218 and actuator 220 via wired connection, wireless connection or a combination thereof.
[0054] like Figure 2B As shown, controller 212 may include electronic processor 230, input / output (I / O) interface 232, and data storage device 234. However, it should be understood that controller 212 may have more or fewer components suitable for the application and setup, such as multiple electronic processors, multiple I / O interfaces, multiple data storage devices, or combinations thereof. In some embodiments, some or all of the components included in controller 212 may be attached to one or more motherboards and enclosed in a housing (e.g., including plastic, metal, and / or other materials). In some embodiments, some of these components may be fabricated on a single system-on-a-chip (SoC) (e.g., an SoC may include one or more processing devices and one or more storage devices).
[0055] As used herein, the term “processor” or “electronic processor” means any device or part of a device that processes electronic data from registers and / or memory to convert that electronic data into other electronic data that can be stored in registers and / or memory.
[0056] Data storage device 234 may include one or more memory devices, such as random access memory (RAM) devices, hard disk-based memory devices, solid-state memory devices, network drives, cloud drives, or any other memory devices. In some implementations, data storage device 234 may include a non-transitory computer-readable medium having instructions on it that, when executed by one or more processors (e.g., processor 230), cause controller 212 to perform any suitable method or portion thereof of the methods disclosed herein. For example, one or more data storage devices 234 included in controller 212 may store various applications and data for performing one or more of the methods described herein or portions thereof. For example, one or more data storage devices 234 may store a liquid analysis program 236, stepper motor positions 238 for positioning bases 202 and 204 at multiple different intervals, reference images 240 used by one or more of the described methods, or combinations thereof. It should be understood that each method described herein may be implemented via one or more applications.
[0057] The I / O interface 232 of the controller 212 may include one or more communication chips, connectors and / or other hardware and software to manage communication between the controller 212 and other components, such as the user interface 224.
[0058] In some embodiments, the liquid analysis system 200 provides a standalone or dedicated instrument or apparatus (or group of instruments or apparatuses) configured to measure the electrochemical properties of a liquid sample. However, in other embodiments, the liquid analysis system may be configured to perform additional measurements or analyses of the liquid sample, including, for example, additional measurements or analyses of the sample's physical and / or optical properties. Combining such measurements or analyses in a single system (e.g., a single instrument) results in more efficient and accurate analysis because the same sample can be measured multiple times without changing the sample's location, moving the sample to different instruments, or using separate samples with the same solution in different instruments, all of which can lead to the possibility of delays and contamination or unexpected differences between measurements.
[0059] Figure 3 Another liquid analysis system 300 (“System 300”) is illustrated, wherein System 100 may be implemented in some examples. System 300 can measure the electrochemical and optical properties of the same sample positioned between surfaces. In some examples, the measurements of electrochemical and optical properties can be performed simultaneously. Figure 3As shown, the liquid analysis system 300 includes components similar to those of the liquid analysis system 200 described above. Specifically, the system 300 includes bases 202 and 204 for holding the sample 210 via surface tension and sample-facing surfaces 206 and 208, a controller 212, one or more electrical connections (e.g., wires) 214 and 216, a camera 218, a first electrode 226 and a second electrode 228, an actuator 220 (e.g., one or more stepper motors), and an electronic processing unit 222. Thus, utilizing these components, the system 300 is configured to perform electrochemical measurements and analyses as described herein.
[0060] However, as Figure 3 As shown, the liquid analysis system 300 also includes a first optical fiber 302 connected to a light source 304 and a second optical fiber 306 connected to a detector 308. Optical fibers 302 and 306 may have ends that are part of sample-facing surfaces 206 and 208. One fiber is the source, and the other is the receiver. The optical fibers may be coaxial with and perpendicular to the parallel surfaces. For example, in this configuration, the liquid analysis system 300 may include a detector. The detector may include a spectrometer for dispersing light based on its wavelength. Such an instrument is configured to quantitatively measure the reflectance or other optical transmission properties of a sample, which can be used to determine the amount of a specific compound in the sample.
[0061] In some examples, optical fibers 302 and 306 can be replaced by miniature light sources such as light-emitting diodes (LEDs). Small solid-state detectors with associated filters, such as those used in color charge-coupled devices (CCDs) for imaging, can replace the receiving optical fiber and detector.
[0062] Combining the electrochemical measurements and analyses described herein with the optical-based measurements offered by such optical instruments facilitates the performance of different types of measurements on the same sample located within the instrument, as described above, resulting in efficiency and improved data collection and related processing.
[0063] It should be understood that although the embodiments described herein are used in conjunction with a spectrophotometer or other optical instruments, the embodiments can be constructed as stand-alone devices (i.e., without optical instrumentation components) for measuring the electrochemical properties (e.g., conductivity) of microvolume liquid samples. Furthermore, while some embodiments are described herein with reference to the temperature of the sample, the methods and systems described herein can also be used to measure other electrochemical properties, such as the conductivity, resistance, pH, etc. of the sample.
[0064] It should be understood that the measurement methods described herein can be performed by various types of optical measuring instruments for detecting the optical properties of a liquid sample positioned between the sample-facing surface 206 and the sample-facing surface 208, and are not limited to these methods. Figure 3The example systems shown or examples of such instruments described herein are examples of types or brands. For example, as mentioned above, in some embodiments, the optical fiber may be replaced by a miniature light source (such as an LED) and a detector with optical filters (e.g., a solid-state detector). Furthermore, as mentioned above, in some embodiments, the optical measurement apparatus may have different surface orientations for holding the sample 210, including, for example, a vertical orientation. It should also be understood that in some embodiments, the detection of the optical properties of the sample 210 positioned between the sample-facing surfaces 206 and 208 can occur simultaneously with at least some portions of the measurement methods described herein, which can provide further efficiency in sample analysis.
[0065] about Figure 3 In the example liquid analysis system 300, light from a light source 304 passes through a first optical fiber 302 positioned in a base 202, radiating downwards through a sample 210 and being collected by a second optical fiber 306, which can be used as a light guide. It should be understood that light can pass through the sample 210 in either direction and is not limited to downward transmission through the first optical fiber 302. A detector 308 receives the collected light. The concentration of a specific component in the sample 210 can be determined based on the collected light.
[0066] In some implementations, controller 212 may enable the display of communications on, for example, a display device, to inform the user of the electrochemical properties of a sample of the microvolume of liquid of interest. Alternatively or otherwise, controller 212 may output the determined electrochemical properties to one or more external devices, networks, or data storage devices. The data may be provided in its raw form, as part of a report, or a combination thereof. One or more alarms may also be generated based on the determined electrochemical properties, such as, for example, to warn the user of errors, out-of-range conductivity, etc.
[0067] Figure 4 A circuit diagram 400 is shown that can be used to determine the conductivity of a sample for temperature measurement. (See diagram 400.) Figure 4 As shown, AC voltage source 402 can be configured to supply any suitable AC signal. A first voltage difference (Vresistor) is measured across resistor 404, and a second voltage difference (Vsolution) is measured across sample 210. Resistor 404 can have any suitable value. For example, in some examples, resistor 404 can be a 1kΩ resistor. For conductivity measurements, the AC signal applied across sample 210 includes both positive and negative voltages, such that ions in sample 210 do not preferentially accumulate on one of the electrodes (e.g., electrodes 226 or 228). Additionally, the voltage amplitude of the applied AC signal should be sufficiently low (e.g., 6V or lower) to avoid electrolysis.
[0068] The resistance of sample 210 can be determined by measuring the voltage and current flowing through it. The conductivity (k) is the resistance (R) of sample 210 weighted by the geometry of the measuring electrodes (called the electrode constant), as shown in equation (1) below. The electrode constant can be predetermined in the calibration process described in patent application WO2024173752A1.
[0069] The electrical signal applied across the sample may have an oscillation frequency. The electrical signal may have any suitable oscillation frequency appropriate for a particular implementation. For example, as mentioned above, the electrical signal may have an oscillation frequency of 20 kHz as an AC signal. In some alternative implementations, an oscillation frequency of 10 kHz, 30 kHz, or any other suitable oscillation frequency may be used. The first frequency may be a first frequency component of the electrical signal, and the second frequency may be a second frequency component of the electrical signal. The second frequency may be a harmonic of the first frequency. The second frequency may be considered a first useful additional harmonic (e.g., the third harmonic). For example, if the oscillation frequency is 20 kHz, the first frequency may correspond to a 20 kHz harmonic of the measured voltage of the electrical signal (e.g., the first harmonic), and the second frequency may correspond to a 60 kHz harmonic of the electrical signal (e.g., the third harmonic).
[0070] Figure 5A and Figure 5B Examples of voltage traces that can be obtained on resistor 404 and sample 210 are shown in some examples. Figure 5A and Figure 5B The example voltage trace shown is from conductivity measurements performed on a 2µl KCl solution droplet by applying a 20kHz square wave. Figure 5A The voltage trace of 500A acquired on resistor 404 is shown, and Figure 5B The voltage trace 500B acquired from sample 210 is shown. Figure 5A and Figure 5B At the oscillation frequency shown, the interaction between the voltage and resistor 404, as well as with sample 210 alone, results in a non-perfect square wave waveform. However, both waveforms shown are uniformly periodic and oscillate at a frequency of 20 kHz, which is helpful for the conductivity and temperature analysis described herein.
[0071] For a given sample, Fourier analysis can be applied to each of the acquired trajectories. When examining square or square-wave-like waveforms, odd harmonics (n=1,3,5,7…) have the highest contribution. Figures 6A to 6C An example of Fourier analysis is shown, where the trace recorded from sample 210 is decomposed into multiple harmonics. Figure 6AIn Figure 600A, the correlation voltage for a single time period acquired on sample 210 is depicted, along with the reconstruction of the data using (n=1,3,5,7…) Fourier components. Figure 6B Chart 600B includes a 20kHz component. Figure 6C The graph for the 60kHz component is shown in Figure 600C. (As shown) Figure 6B and Figure 6C As shown, the 20kHz and 60kHz harmonics are pure sine waves. The 100kHz and 140kHz components are not shown. However, it should be understood that they are also pure sine waves, but due to the sampling rate of the ADC converter, there may be slight asymmetries. Each frequency component extracted from the electrical signal can be analyzed like an independent waveform.
[0072] For the purposes of this specification, the 20kHz and 60kHz components are analyzed only within one fundamental frequency cycle. However, it should be understood that in other specific embodiments, other fundamental frequencies (e.g., 10kHz, 30kHz, etc.) and / or other combinations of useful harmonics may be analyzed to determine conductivity.
[0073] Once the harmonic components are extracted from the measured waveform, the actual voltage used to calculate the conductivity is the root mean square (RMS) value (V) shown in equation (2) below. RMS ).
[0074] In equation (2), (n) is the number of measured data points, (V i ) is the voltage at time (i), for example, at Figure 5A and Figure 5B In the voltage trace shown. System 100 is configured to perform this analysis within a fundamental frequency (20 kHz) cycle to generate voltages Vsolution and Vresistor at two frequencies of interest (20 kHz and 60 kHz). Using these two voltages (Vsolution and Vresistor) calculated at each oscillation frequency, the resistance (Rsolution) of the sample can be calculated using the following equation (3).
[0075] At each oscillation frequency, the resistance of the solution and the known electrode constant can be substituted into equation (1) to determine the first and second conductivity of sample 210. Each oscillation frequency (20 kHz and 60 kHz) examined using Fourier transform has its own corresponding resistance and conductivity values for sample 210.
[0076] Figure 7Figure 700 shows the experimental results, in which the conductivity of various salt solutions was determined at two oscillation frequencies and two temperatures (room temperature ((RT) ~ 22°C) and 25°C). Figure 7 As shown, conductivity measurements at different oscillation frequencies yield different results. For example, the conductivity measured using a faster harmonic (60 kHz) is higher than the corresponding measurement obtained using a slower harmonic (20 kHz). Furthermore, the difference (resolution) between the conductivity extracted from the 20 kHz and 60 kHz harmonics increases with increasing salt solution concentration. For instance, the conductivity of a 0.03 M salt solution obtained at both frequencies is numerically much closer to the conductivity collected from a 0.12 M sample.
[0077] Even if the system temperature changes, Figure 7 The trend shown is consistent. Typically, the conductivity of the sample changes linearly with temperature. For example... Figure 7 As shown, the rate of change of conductivity with temperature increases with the amount of electrolyte in the sample. Because the conductivity of a given electrolyte sample changes linearly with temperature, the difference between the conductivity measured at 20 kHz and 60 kHz for a given sample also changes linearly. Therefore, within the analyzed conductivity range, the conductivity difference between two conductivity measurements at the two oscillation frequencies (20 kHz and 60 kHz) is conserved regardless of temperature.
[0078] Figure 8 Figure 800 shows the conductivity difference between the 20 kHz and 60 kHz components at each temperature for various different salt solutions. Figure 8 In the example shown, the difference between the conductivity measured at 20 kHz and the corresponding conductivity measured at 60 kHz increases with increasing sample conductivity. Typically, the magnitude of this conductivity difference is conserved for each sample measured at the measurement temperature. Furthermore, each of the measured conductivities increases with increasing temperature. As will be further described herein, such as Figure 7 and Figure 8 The information shown can be used as reference data to help determine the temperature of the sample. Although Figure 8 Data related to salt solutions of different concentrations are shown, but it should be understood that... Figure 8 The results shown represent calibration curves that can be used to analyze the conductivity differences of different concentrations in other solutions, such as lysine broth (LB), phosphate-buffered saline (PBS), Tris-EDTA buffer (TE), etc.
[0079] In practice, samples will be measured without prior knowledge of their conductivity or the precise temperature at the time of measurement. Furthermore, the ion concentration of the sample may also be unknown beforehand. Instead, system 100 is configured to determine a first and a second conductivity of the sample, as described herein, to aid in determining the sample's temperature.
[0080] When the ion concentration is unknown, system 100 can determine the ion concentration of the sample. This can be achieved by any suitable method. For example, system 100 can compare the difference between the first conductivity and the second conductivity with reference data (such as...) Figure 8 The data shown is compared. Using the difference in conductivity, it is possible to determine which values fall within the range of conductivity differences. Figure 8 The position on the calibration curve in the reference data is used to estimate the ion concentration. For example, system 100 can determine a conductivity difference of approximately 3500 μS / cm. Based on this, system 100 can estimate the ion concentration based on a 0.1 M position... Figure 8 The ion concentration of the sample was determined to be 0.1 M based on the calibration curve below 3500.
[0081] Based on ion concentration, system 100 can determine the temperature of the sample by comparing a first amplitude of a first conductivity and / or a second amplitude of a second conductivity with additional reference data. Figure 9 A graph 900 is shown, including example reference data that can be used to determine sample temperature. (Utilizing...) Figure 9 The information shown allows for a comparison of the amplitudes of the first and second conductivity. Figure 9 The reference measurement results shown are plotted to determine the temperature. This can be achieved in any suitable manner. For example, system 100 can be based on... Figure 9 The reference data represented in the figure generates multiple calibration curves. For example, at a concentration of 0.1 M, the black circles, white circles, and black squares indicate that the conductivity at 20 kHz increases with temperature. Based on this relationship, system 100 can generate a first calibration curve for 20 kHz data at a 0.1 M concentration to determine the temperature of the sample at that concentration and conductivity amplitude. For example, if the amplitude of the first conductivity of the 0.1 M sample is close to 8000 μS / cm, system 100 can determine the temperature to be 31 °C. On the other hand, if the amplitude of the first conductivity of the 0.1 M sample is close to 6000 μS / cm, system 100 can determine the temperature of the sample to be RT or lower. System 100 can... Figure 9 Each data point in the data cluster represented in the diagram generates a different calibration curve. For example, system 100 can generate a second calibration curve for 60 kHz data at a concentration of 0.1 M (e.g., data indicated by white squares, white stars, and black stars at 0.1 M). Similarly, system 100 can generate a second calibration curve for 60 kHz data at a concentration of 0.1 M. Figure 9 Additional calibration curves are generated from other concentration / frequency data represented in the figure.
[0082] In some examples, for each of the 20 kHz and 60 kHz components, a global linear fit can be applied to estimate the conductivity versus temperature curves of reference data acquired at RT, 25 °C, and 31 °C. The conductivity measured at 20 kHz and 60 kHz can then be compared to these curves to determine the temperature. This can be done, for example, by determining the location where the difference between the measurement point and the reference point is minimal. However, any other suitable algorithm can be used in alternative implementations.
[0083] Figure 10 An example flowchart 1000 is shown, depicting various operations that the system 100 can perform when determining the temperature of a sample. For example... Figure 10 As shown, system 100 can measure the conductivity of a sample at operation 1002. Operation 1002 can be performed in any of the ways described herein.
[0084] At operation 1004, system 100 can calculate the conductivity of the sample using a first frequency harmonic and a second frequency harmonic. Operation 1004 can be performed in any of the ways described herein. For example, the first frequency harmonic can be a 20 kHz component of an AC signal applied across the sample, and the second frequency harmonic can be a 60 kHz component of the AC signal.
[0085] At operation 1006, system 100 can determine the ion concentration of the sample based on a comparison of the conductivity difference calculated at operation 1004 with reference data. Operation 1006 can be performed in any of the ways described herein. For example, the reference data may include... Figure 8 The information shown is similar to the information provided. System 100 can base its information on the difference in conductivity falling within the range of... Figure 8 The position of the data points on the calibration curve associated with them is used to determine the ion concentration along the x-axis.
[0086] At operation 1008, system 100 can determine the temperature at the determined concentration based on a comparison of the calculated conductivity with additional reference data. Operation 1008 can be performed in any of the ways described herein. For example, the additional reference data may include, for instance, the temperature calculated by comparing the calculated conductivity with additional reference data with additional reference data. Figure 9 The data shown. System 100 can use, for example... Figure 9 The information shown is used to generate a calibration curve that correlates temperature and conductivity for a given ion concentration.
[0087] At operation 1010, system 100 can determine the corrected electrochemical properties of a sample at a baseline temperature (e.g., 25°C). The baseline temperature is a predetermined reference temperature at which the electrochemical properties of the sample are normalized or reported, independent of the actual temperature at which the sample is measured. For example, system 100 can determine the corrected conductivity, corrected pH, and / or any other suitable corrected electrochemical properties of the sample based on the sample temperature determined at 1008. The corrected electrochemical properties can be generated via mathematical calculations or based on reference data. The system can provide the user with an indication of the corrected electrochemical properties of the sample at the baseline temperature.
[0088] For example, when the determined sample temperature is no higher than 37°C, system 100 corrects the measured conductivity based on a temperature coefficient. When determining the corrected conductivity, system 100 can determine the temperature coefficient of change (α). c (α), which describes how the conductivity of a sample, measured at a reference temperature, changes with unit temperature (typically 1°C). According to industry standards, (α) c α is set to equal 2%. c The 2% value represents most ion-based biological buffers currently in use. Additionally, it practically assumes a temperature below 37°C. These two assumptions are consistent with the expected and common use of sample analysis equipment, allowing for the use of 2% (α) buffers. c ). Using a fixed (α) c The value can be obtained using the following equation (4) based on the measured conductivity (C). meas Determine the conductivity (C) corrected to 25°C. 25 ).
[0089] (4) Variable (T) meas The temperature at which the actual sample conductivity was measured is denoted as . This equation enforces a linear relationship between the measured conductivity and temperature. As mentioned, this relationship is valid for most ion-based buffer solutions measured at temperatures below 37°C.
[0090] In another example, when measurements need to be taken outside the aforementioned temperature range (e.g., above 37°C), the linear relationship between temperature and the measured conductivity may fail. Therefore, the conductivity of the sample at these higher temperatures can be corrected based on reference data, such as calibration curves generated using a reference sample. The reference sample can be selected to resemble the possible composition of the sample of interest (i.e., the sample from which conductivity is measured). For example, the sample of interest might be a protein in a PBS solution. A calibration curve for this sample of interest can be obtained by measuring the conductivity of the PBS solution at various temperatures. For samples at temperatures above 37°C, a calibration curve can be generated by using a complex polynomial fit to the conductivity versus temperature data of the reference sample to extract the conductivity versus temperature relationship that can be directly used to correct conductivity.
[0091] In some examples, the pH level of a sample is measured by acquiring the open-circuit signal of the sample, as presented in patent application WO2024173752A1. The temperature of the sample can be determined before or after the pH measurement using the method of Chart 1000. To correct the measured pH value based on the temperature of the sample, System 100 can compare the measured data with a pre-generated pH vs. temperature dataset curve. The curve can be pre-measured from multiple reference samples with known pH values at various temperatures. Fitting the pH vs. temperature for a given sample of interest provides information about the amount of pH change to correct the measured pH to the baseline temperature. When pH and temperature are measured on the same sample and that sample has a reference (pH vs. temperature) dataset, analysis of the curve will deduce the change in pH based on the difference between the pH value at the measurement temperature and the pH value at the baseline temperature.
[0092] In some examples, system 100 may be configured to provide a user with information relating to the properties of a sample. This can be achieved in any suitable manner. For example, system 100 may provide a user with one or more graphical user interface (GUI) views for display via a display device, the one or more GUI views having information indicating any suitable properties associated with the sample. In some specific implementations, system 100 may be configured to provide an indication of the sample at a determined temperature to the user. Additionally or alternatively, system 100 may be configured to provide an indication of the conductivity of the sample at a determined temperature to the user. In such examples, system 100 may be configured to determine the conductivity of the sample at a determined temperature in any suitable manner (as described herein).
[0093] Additionally or alternatively, system 100 may be configured to provide the user with corrected electrochemical properties of the sample at a baseline temperature (e.g., 25°C, room temperature, etc.) for display. For example, system 100 may display the corrected conductivity of the sample, the corrected pH value of the sample, and / or any other suitable corrected electrochemical properties.
[0094] Figure 11 An example graphical user interface view 1100 is illustrated, which can be provided to display to the user the results of temperature and conductivity measurements of a sample. Figure 11 As shown, the graphical user interface view 1100 includes a results pane 1102, which provides information about the sample's measurement temperature, the sample's conductivity at the measurement temperature, and the sample's corrected conductivity at a baseline temperature of 25°C.
[0095] Figure 12 An example method 1200 for analyzing micro-volume samples is illustrated. Although Figure 12 Example operations based on one implementation are illustrated, but other specific implementations may omit, add, reorder, and / or modify them. Figure 12 Any operation shown. Figure 12 One or more of the operations shown can be performed by a system (such as system 100), any of its components and / or any specific implementation thereof.
[0096] At operation 1202, the sample is positioned between a first surface and a second surface of a sample analysis system (e.g., sample analysis system 100), wherein the sample is held between the first surface and the second surface by surface tension. Operation 1202 can be performed in any of the manner described herein. In some examples, system 100 may determine whether the sample is positioned between the first surface and the second surface. For example, system 100 may confirm contact between the sample and a conductive portion of the base of the sample analysis device (e.g., base 202 / 204) based on electrical signals applied to both ends of the sample. Additionally or alternatively, system 100 may analyze images captured by a camera (e.g., camera 218) to determine whether the sample is positioned between the first surface and the second surface.
[0097] At operation 1204, the sample analysis system (e.g., sample analysis system 100) may apply at least one electrical signal to both ends of the sample via a first electrode associated with the first surface and a second electrode associated with the second surface. Operation 1204 may be performed in any of the manner described herein.
[0098] At operation 1206, the sample analysis system can determine, based on the at least one electrical signal applied to both ends of the sample, a first conductivity of the sample at a first frequency associated with the at least one electrical signal and a second conductivity of the sample at a second frequency associated with the at least one electrical signal. Operation 1206 can be performed in any of the manner described herein.
[0099] At operation 1208, the sample analysis system can determine the temperature of the sample based on a first conductivity and a second conductivity. Operation 1208 can be performed in any of the manner described herein.
[0100] At operation 1210, the sample analysis system can determine the electrochemical properties of the sample. Operation 1210 can be performed in any of the ways described herein.
[0101] At operation 1212, the sample analysis system can generate a value representing the electrochemical properties of the sample at a baseline temperature based on the determined electrochemical properties of the sample and the determined temperature.
[0102] In some instances, a non-transitory computer-readable medium may be provided for storing computer-readable instructions, based on the principles described herein. When executed by a processor of a computing device, the instructions may direct the processor and / or the computing device to perform one or more operations, including one or more operations described herein. Any computer-readable medium of a variety of known computer-readable media may be used to store and / or transmit such instructions.
[0103] As used herein, non-transitory computer-readable media can include any non-transitory storage medium that contributes to providing data (e.g., instructions) that can be read and / or executed by a computing device (e.g., by a processor of the computing device). For example, non-transitory computer-readable media can include, but is not limited to, any combination of non-volatile storage media and / or volatile storage media. Exemplary non-volatile storage media include, but are not limited to, read-only memory, flash memory, solid-state drives, magnetic storage devices (e.g., hard disks, floppy disks, magnetic tapes, etc.), ferroelectric random access memory (“RAM”), and optical discs (e.g., compact discs, digital video discs, Blu-ray discs, etc.). Exemplary volatile storage media include, but are not limited to, RAM (e.g., dynamic RAM).
[0104] Figure 13 An example computing device 1300 is illustrated, which may be specifically configured to perform one or more processes described herein. Figure 13 As shown, computing device 1300 may include a communication interface 1302, a processor 1304, a storage device 1306, and an input / output (“I / O”) module 1308 that are communicatively connected to each other via communication infrastructure 1310. Although Figure 13Example computing device 1300 is shown, but Figure 13 The components illustrated are not intended to be limiting. Additional or alternative components may be used in other specific implementations. A more detailed description will follow. Figure 13 The components of the computing device 1300 shown.
[0105] Communication interface 1302 can be configured to communicate with one or more computing devices. Examples of communication interface 1302 include, but are not limited to, wired network interfaces (such as network interface cards), wireless network interfaces (such as wireless network interface cards), modems, audio / video connections, and any other suitable interfaces.
[0106] Processor 1304 generally refers to any type or form of processing unit capable of processing data and / or interpreting, executing, and / or directing one or more of the instructions, procedures, and / or operations described herein. Processor 1304 may perform operations by executing computer-executable instructions 1312 (e.g., applications, software, code, and / or other executable data instances) stored in storage device 1306.
[0107] Storage device 1306 may include one or more data storage media, devices, or configurations, and may take the form of any type, form, and combination of data storage media and / or devices. For example, storage device 1306 may include, but is not limited to, any combination of non-volatile media and / or volatile media described herein. Electronic data (including the data described herein) may be stored temporarily and / or permanently in storage device 1306. For example, data representing computer-executable instructions 1312 configured to boot processor 1304 to perform any of the operations described herein may be stored within storage device 1306. In some examples, data may be arranged in one or more databases residing within storage device 1306.
[0108] I / O module 1308 may include one or more I / O modules configured to receive user input and provide user output. One or more I / O modules may be used to receive input for a single virtual experience. I / O module 1308 may include any hardware, firmware, software, or a combination thereof that supports input and output capabilities. For example, I / O module 1308 may include hardware and / or software for capturing user input, including but not limited to a keyboard or keypad, a touchscreen component (e.g., a touchscreen display), a receiver (e.g., an RF or infrared receiver), a motion sensor, and / or one or more input buttons.
[0109] I / O module 1308 may include one or more devices for presenting output to a user, including but not limited to a graphics engine, a display (e.g., a screen), one or more output drivers (e.g., a display driver), one or more audio speakers, and one or more audio drivers. In some embodiments, I / O module 1308 is configured to provide graphical data to a display for presentation to a user. The graphical data may represent one or more graphical user interfaces and / or any other graphical content that may be available for a particular embodiment.
[0110] In some examples, any system, computing device, and / or other component described herein may be implemented by computing device 1300. For example, processor 108, controller 212, and / or electronic processing unit 222 may be implemented by processor 1304.
[0111] The following statements further describe the advantages and features of this disclosure: 1. A system for analyzing a sample, the system comprising: a first surface including at least a portion of a first electrode; a second surface including at least a portion of a second electrode, the second surface being positioned relative to the first surface for holding the sample between the first surface and the second surface by surface tension; and an electronic processing unit configured to: apply at least one electrical signal at both ends of the sample via the first electrode and the second electrode; determine, based on the at least one electrical signal applied at both ends of the sample, a first conductivity of the sample at a first frequency associated with the at least one electrical signal and a second conductivity of the sample at a second frequency associated with the at least one electrical signal; and determine a temperature of the sample based on the first conductivity and the second conductivity.
[0112] 2. The system according to the foregoing statement, wherein applying the at least one electrical signal includes applying an AC electrical signal across the sample.
[0113] 3. The system according to any one of the foregoing statements, wherein: the at least one electrical signal comprises an electrical signal having a plurality of frequency components; the first frequency is a first frequency component among the plurality of frequency components; and the second frequency is a second frequency component among the plurality of frequency components.
[0114] 4. The system of claim 1, wherein the at least one electrical signal comprises a first electrical signal and a second electrical signal, and the first conductivity of the sample at a first frequency associated with the at least one electrical signal and the second conductivity of the sample at a second frequency associated with the at least one electrical signal are determined.
[0115] 5. The system according to statements 1 to 3, wherein the second frequency is a harmonic of the first frequency.
[0116] 6. The system according to any one of the foregoing statements, wherein: the electronic processing unit is further configured to determine the ion concentration of the sample; and the determination of the temperature of the sample is based on the determination of the ion concentration of the sample.
[0117] 7. The system according to the foregoing statement, wherein determining the ion concentration of the sample comprises: determining a difference between the first conductivity and the second conductivity; and determining the ion concentration of the sample based on a comparison of the difference with reference data.
[0118] 8. The system according to any one of the foregoing statements, wherein determining the temperature of the sample comprises: determining a first amplitude of the first conductivity and a second amplitude of the second conductivity; and determining the temperature of the sample based on a comparison of the first amplitude and the second amplitude with additional reference data.
[0119] 9. The system according to any one of the foregoing statements, wherein the electronic processing unit is further configured to provide an indication of the determined temperature of the sample to be presented to the user.
[0120] 10. The system according to any one of the foregoing statements, wherein the electronic processing unit is further configured to: determine the conductivity of the sample at a determined temperature based on the first conductivity and / or the second conductivity; and provide an indication of the conductivity of the sample at the determined temperature to a user.
[0121] 11. The system according to any one of the foregoing statements, wherein the electronic processing unit is further configured to: determine the electrochemical properties of the sample at a determined temperature; determine the corrected electrochemical properties of the sample at a baseline temperature based on the electrochemical properties of the sample at the determined temperature and the determined temperature; and provide an indication of the corrected electrochemical properties of the sample at the baseline temperature to a user.
[0122] 12. The system according to the foregoing statement, wherein the electrochemical property includes conductivity, and determining the electrochemical property of the sample at a determined temperature includes determining the conductivity of the sample at the determined temperature based on the first conductivity and / or the second conductivity.
[0123] 13. The system according to statement 11, wherein the electrochemical property includes pH value, and determining the electrochemical property of the sample at a determined temperature includes performing a pH measurement of the sample at the determined temperature.
[0124] 14. A computer program product, the computer program product being contained in a non-transitory computer-readable storage medium and including computer instructions for performing a process comprising: determining that a sample is positioned between a first surface and a second surface, wherein the sample is held between the first surface and the second surface by surface tension; applying at least one electrical signal at both ends of the sample via a first electrode associated with the first surface and a second electrode associated with the second surface; determining, based on the at least one electrical signal applied at both ends of the sample, a first conductivity of the sample at a first frequency associated with the at least one electrical signal and a second conductivity of the sample at a second frequency associated with the at least one electrical signal; and determining a temperature of the sample based on the first conductivity and the second conductivity.
[0125] 15. The computer program product according to the foregoing statement, wherein applying the at least one electrical signal includes applying an AC electrical signal to both ends of the sample.
[0126] 16. The computer program product according to the foregoing statement, wherein: the AC electrical signal has a plurality of frequency components; the first frequency is a first frequency component among the plurality of frequency components; and the second frequency is a second frequency component among the plurality of frequency components.
[0127] 17. The computer program product according to statement 14, wherein the second frequency is a harmonic of the first frequency.
[0128] 18. The computer program product according to any one of the foregoing statements, wherein: the process further includes determining the ion concentration of the sample; and determining the temperature of the sample is based on determining the ion concentration of the sample.
[0129] 19. The computer program product according to the foregoing statement, wherein determining the ion concentration of the sample comprises: determining a difference between the first conductivity and the second conductivity; and determining the ion concentration of the sample based on a comparison of the difference with reference data.
[0130] 20. The computer program product according to any one of the foregoing statements, wherein determining the temperature of the sample comprises: determining a first amplitude of the first conductivity and a second amplitude of the second conductivity; and determining the temperature of the sample based on a comparison of the first amplitude and the second amplitude with additional reference data.
[0131] 21. The computer program product according to any one of the foregoing statements, wherein the process further comprises: determining the conductivity of the sample at a determined temperature based on the first conductivity and the second conductivity.
[0132] 22. The computer program product according to the foregoing statement, wherein the process further comprises: determining a corrected conductivity of the sample at a baseline temperature based on a determined temperature and the conductivity of the sample at the determined temperature; and providing an indication of the corrected conductivity of the sample at the baseline temperature to the user.
[0133] 23. A method for measuring the electrochemical properties of a sample includes: providing a sample positioned between a first surface and a second surface of a sample analysis system, wherein the sample is held between the first surface and the second surface by surface tension; applying at least one electrical signal by the sample analysis system at both ends of the sample via a first electrode associated with the first surface and a second electrode associated with the second surface; determining, based on the at least one electrical signal applied at both ends of the sample, a first conductivity of the sample at a first frequency associated with the at least one electrical signal and a second conductivity of the sample at a second frequency associated with the at least one electrical signal; determining, by the sample analysis system, a temperature of the sample based on the first conductivity and the second conductivity; determining, by the sample analysis system, the electrochemical properties of the sample; and generating, by the sample analysis system, a value representing the electrochemical properties of the sample at a baseline temperature based on the determined electrochemical properties of the sample and the determined temperature.
[0134] 24. The method according to the foregoing statement, wherein applying the at least one electrical signal includes applying an AC electrical signal to both ends of the sample.
[0135] 25. The method according to any one of the preceding statements, wherein: the at least one electrical signal has a plurality of frequency components; the first frequency is a first frequency component among the plurality of frequency components; and the second frequency is a second frequency component among the plurality of frequency components.
[0136] 26. The method described above, wherein the second component of the oscillation frequency is a harmonic of the first frequency.
[0137] 27. The method according to any one of the foregoing statements, the method further comprising determining the ion concentration of the sample by the sample analysis system, wherein determining the temperature of the sample is based on determining the ion concentration of the sample.
[0138] 28. The method described above, wherein determining the ion concentration of the sample comprises: determining a difference between the first conductivity and the second conductivity; and determining the ion concentration of the sample based on a comparison of the difference with reference data.
[0139] 29. The method according to any one of the foregoing statements, wherein determining the temperature of the sample comprises: determining a first amplitude of the first conductivity and a second amplitude of the second conductivity; and determining the temperature of the sample based on a comparison of the first amplitude and the second amplitude with the additional reference data.
[0140] 30. The method according to statement 23 above, wherein determining the electrochemical properties includes measuring the pH and / or conductivity of the sample.
[0141] 31. The method according to statement 23, wherein the second frequency is higher than 50 kHz and the first frequency is not greater than 50 kHz.
[0142] 32. The method of claim 31, wherein the difference between the first frequency and the second frequency is not less than 20 kHz.
[0143] Various examples, aspects, features, and specific implementations of the systems and methods disclosed herein can advantageously address the aforementioned and other related problems in the prior art. Therefore, incorporating temperature detection into systems and methods for measuring the electrochemical properties of liquid samples is a solution to a technical problem solved using specific computing systems and devices. Consequently, the specific implementations disclosed herein provide improvements to the measurement of the electrochemical properties of liquid samples (e.g., improvements in the computer technology supporting this measurement functionality, and others).
[0144] As described above in the detailed description, reference is made to the accompanying drawings, which form part of the detailed description, wherein like reference numerals always designate like parts, and practical embodiments are illustrated in the drawings by way of example. It should be understood that other embodiments may be utilized, and structural or logical changes may be made, without departing from the scope of this disclosure. Therefore, the detailed description as described above should not be construed as limiting.
[0145] The various operations can be described sequentially as multiple discrete actions or operations in a manner most conducive to understanding the subject matter disclosed herein. However, the described order should not be construed as implying that these operations must depend on a specific order. In particular, these operations may not be performed in the order presented. The described operations may be performed in a different order than the described implementation. Various additional operations may be performed, and / or the described operations may be omitted in other specific implementations.
[0146] For the purposes of this disclosure, the phrases "A and / or B" and "A or B" mean (A), (B), or (A and B). For the purposes of this disclosure, the phrases "A, B and / or C" and "A, B or C" mean (A), (B), (C), (A and B), (A and C), or (A, B and C). Although some elements may be represented in the singular (e.g., "processing device"), any suitable element may be represented by multiple instances of those elements, and vice versa. For example, a set of operations described as being performed by a processing device may be implemented as different operations among those operations performed by different processing devices.
[0147] This specification uses the phrases “implementation,” “various implementations,” and “some implementations,” each of which may refer to one or more of the same or different implementations or specific embodiments. Furthermore, the terms “comprising,” “including,” “having,” etc., used with respect to specific embodiments of this disclosure are synonymous. When used to describe a range of values, the phrase “between X and Y” indicates a range including both X and Y. As used herein, “apparatus” and / or “system” may refer to any single device, a collection of devices, a portion of a device, or a collection of portions of a device. The figures are not necessarily drawn to scale.
Claims
1. A system for analyzing samples, the system comprising: A first surface, the first surface including at least a portion of a first electrode; A second surface, comprising at least a portion of a second electrode, is positioned relative to the first surface for holding the sample between the first and second surfaces by surface tension. and Electronic processing unit, the electronic processing unit being configured to: At least one electrical signal is applied to both ends of the sample via the first electrode and the second electrode; Based on the at least one electrical signal applied to both ends of the sample, determine a first conductivity of the sample at a first frequency associated with the at least one electrical signal and a second conductivity of the sample at a second frequency associated with the at least one electrical signal; and The temperature of the sample is determined based on the first conductivity and the second conductivity.
2. The system according to claim 1, wherein: The at least one electrical signal includes an electrical signal having multiple frequency components; The first frequency is the first frequency component among the plurality of frequency components; and The second frequency is the second frequency component among the plurality of frequency components.
3. The system of claim 1, wherein the at least one electrical signal comprises a first electrical signal and a second electrical signal, and determining the first conductivity of the sample at the first frequency associated with the at least one electrical signal and the second conductivity of the sample at the second frequency associated with the at least one electrical signal comprises: In response to applying the first electrical signal, the first conductivity at the first frequency associated with the first electrical signal and the second conductivity at the second frequency associated with the second electrical signal are determined.
4. The system according to claim 1, wherein the second frequency is a harmonic of the first frequency.
5. The system according to claim 1, wherein: The electronic processing unit is further configured to determine the ion concentration of the sample; and The temperature of the sample is determined based on the determination of the ion concentration of the sample.
6. The system of claim 5, wherein determining the ion concentration of the sample comprises: Determine the difference between the first conductivity and the second conductivity; as well as The ion concentration of the sample is determined by comparing the difference with reference data.
7. The system of claim 1, wherein determining the temperature of the sample comprises: Determine a first amplitude of the first conductivity and a second amplitude of the second conductivity; as well as The temperature of the sample is determined based on a comparison of the first and second amplitudes with additional reference data.
8. The system according to any one of claims 1 to 7, wherein the electronic processing unit is further configured to: The conductivity of the sample at the determined temperature is determined based on the first conductivity and / or the second conductivity; and An indication of the conductivity of the sample at a determined temperature is provided to the user.
9. The system according to any one of claims 1 to 7, wherein the electronic processing unit is further configured to: Determine the electrochemical properties of the sample at the determined temperature; Based on the electrochemical properties of the sample at the determined temperature and the determined temperature, determine the corrected electrochemical properties of the sample at the baseline temperature; and Indications of the corrected electrochemical properties of the sample at the baseline temperature are provided to the user.
10. The system of claim 9, wherein the electrochemical property includes conductivity, and determining the electrochemical property of the sample at a determined temperature includes determining the conductivity of the sample at the determined temperature based on the first conductivity and / or the second conductivity.
11. The system of claim 9, wherein the electrochemical property includes pH value, and determining the electrochemical property of the sample at a determined temperature includes performing a pH measurement of the sample at the determined temperature.
12. A method for measuring the electrochemical properties of a sample, the method comprising: A sample is provided positioned between a first surface and a second surface of a sample analysis system, wherein the sample is held between the first surface and the second surface by surface tension; The sample analysis system applies at least one electrical signal to both ends of the sample via a first electrode associated with the first surface and a second electrode associated with the second surface; The sample analysis system determines, based on the at least one electrical signal applied to both ends of the sample, the first conductivity of the sample at a first frequency associated with the at least one electrical signal and the second conductivity of the sample at a second frequency associated with the at least one electrical signal; The temperature of the sample is determined by the sample analysis system based on the first conductivity and the second conductivity. The electrochemical properties of the sample are determined by the sample analysis system. as well as The sample analysis system generates values representing the electrochemical properties of the sample at a baseline temperature based on the determined electrochemical properties of the sample and the determined temperature.
13. The method according to claim 12, wherein: The at least one electrical signal has multiple frequency components; The first frequency is the first frequency component among the plurality of frequency components; and The second frequency is the second frequency component among the plurality of frequency components.
14. The method of claim 13, wherein the second frequency is higher than 50 kHz and the first frequency is not greater than 50 kHz.
15. The method of claim 14, wherein the difference between the first frequency and the second frequency is not less than 20 kHz.
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