US-12618796-B2 - Continuous aptamer sensing devices with improved longevity by gating of sample fluid

Abstract

A device and method for continuously sensing at least one target analyte in a sample fluid. The device 100 includes a plurality of electrochemical aptamer sensors 120, 122, 124, 126 ; and at least one gating component 132, 134, 136 associated with at least one electrochemical aptamer sensor of the plurality of electrochemical aptamer sensors. The method includes bringing a sample fluid 190 into contact with the device, and determining or measuring a change in an electrical current associated with the at least one electrochemical aptamer sensor to (1) determine the presence of an analyte in the sample fluid, or (2) measure the amount or concentration of an analyte in the sample fluid.

Inventors

• Jason Heikenfeld

Assignees

• UNIVERSITY OF CINCINNATI

Dates

Publication Date

20260505

Application Date

20210924

Claims (2)

1. 1 . A method comprising: substantially simultaneously bringing a sample fluid into contact with multiple electrochemical aptamer sensors associated with a device, each electrochemical aptamer sensor of the multiple electrochemical aptamer sensors having a gating component associated therewith; and determining or measuring a change in an electrical current associated with the at least one electrochemical aptamer sensor to (1) determine the presence of an analyte in the sample fluid, or (2) measure the amount or concentration of an analyte in the sample fluid; wherein each gating component includes a property having a value, and wherein the value of the property for each gating component is different than the value of the property for each of the other gating components; and wherein determining or measuring a change in an electrical current associated with the at least one electrochemical aptamer sensor is done multiple times at intervals; and wherein at least one measurement is made of each electrochemical aptamer sensor to determine the presence or absence of the gating component.
2. 2 . The method of claim 1 , where once the absence of the gating component is determined by measurement of the electrochemical aptamer sensor, measurement of the analyte then follows.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to, and the benefit of the filing date of, U.S. Provisional Application No. 63/085,456 filed Sep. 30, 2020 and U.S. Provisional Application No. 63/150,921 filed Feb. 18, 2021, the disclosures of which are incorporated by reference herein in their entireties. TECHNICAL FIELD OF THE INVENTION The present invention relates to the use of electrochemical aptamer sensors. BACKGROUND OF THE INVENTION This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present invention, which are described and/or claimed below. This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of various aspects of the present invention. Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art. Electrochemical aptamer sensors can identify the presence and/or concentration of an analyte of interest via the use of an aptamer sequence that specifically binds to the analyte of interest. These sensors include aptamers attached to an electrode, wherein each of the aptamers has a redox active molecule (redox couple) attached thereto. The redox couple can transfer electrical charge to or from the electrode. When an analyte binds to the aptamer, the aptamer changes shape, bringing the redox couple closer to or further from, on average, the electrode. This results in a measurable change in electrical current that can be translated to a measure of concentration of the analyte. Such electrochemical aptamer sensors may include multiple (2 or 3 or more) electrodes. A major unresolved challenge for electrochemical aptamer sensors is the lifetime of the sensors, especially for applications where continuous operation is required (“continuous” referring to multiple measurements over time by the same device). Electrochemical aptamer sensors are susceptible to degradation due to, among other things, solutes in a fluid sample that are potentially harmful to the sensor (such as nucleases that can degrade the aptamers, or fouling proteins such as albumin) Harmful solutes such as these can reduce the operational life of the sensor, and thus any device including an electrochemical aptamer sensor. Thus, to date, it has been difficult to provide electrochemical aptamer sensors with a lifetime that allows continuous sensing to take place over an extended period of time. Previously, features such as membranes have been used to attempt to block harmful solutes from affecting sensors. However, while membrane protection has been shown to improve aptamer longevity, it is not feasible when the purpose of the sensor is to measure large analytes such as proteins over an extended period of time. While membranes can block harmful solutes (such as those that could foul the sensor or degrade the aptamer), these membranes could also block the protein of interest, such as thrombin or luteinizing hormone. Therefore, for some analytes, there is currently no choice but to expose the sensor to many, or all, of the harmful solutes in a sample fluid such as blood, interstitial fluid, sweat, river water, or other sample fluids. In view of the above, new devices and methods are needed that can provide improved longevity of electrochemical aptamer sensors and related devices for measurement of large analytes such as proteins. Such new devices and methods may also result in improvements for the use of such devices to detect or measure small analytes as well, where inherent degradation mechanisms such as electrode degradation occur regardless of sample fluid content. SUMMARY OF THE INVENTION Certain exemplary aspects of the invention are set forth below. It should be understood that these aspects are presented merely to provide the reader with a brief summary of certain forms the invention might take and that these aspects are not intended to limit the scope of the invention. Indeed, the invention may encompass a variety of aspects that may not be explicitly set forth below. Many of the drawbacks and limitations stated above can be resolved by creating novel and advanced interplays of chemicals, materials, sensors, electronics, microfluidics, algorithms, computing, software, systems, and other features or designs, in a manner that affordably, effectively, conveniently, intelligently, or reliably brings sensing technology into proximity with sample fluids containing at least one analyte of interest to be measured. Various aspects of the present invention serve to reduce and/or eliminate the drawbacks of current electrochemical aptamer sensors described above. By doing so, aspects of the present invention provide an electrochemical aptamer sensor, device, and method that includes improved longevity of the device. To that end, one aspect of the present invention is directed to a device (e.g., a continuous sensing devi