Methods for detecting and quantifying analytes using gas species diffusion
Inventors
Savoy, Steve M. • Hoover, Kyle W. • Mitchell, Daniel R. • John, Jeremy J. • Mann, Chris W. • Greis, Alexander P.
Assignees
Publication Number
US-10386351-B2
Publication Date
2019-08-20
Expiration Date
2036-12-07
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Abstract
Methods and sensors for detection and quantification of one or more analyte in a test sample are described. A response profile of a gas sensor to a control sample of a known interrogator gas is determined. The gas sensor is exposed to a test sample then to a second sample comprising the known interrogator gas, and a test sample response profile of the gas sensor is determined. One or more test sample sensor response profiles are compared with one or more control sensor response profiles for detecting, identifying, and quantifying one or more analytes in the test sample.
Core Innovation
The invention provides methods and sensors for the detection and quantification of one or more analytes in a test sample by exposing a gas sensor derivatized with analyte binders to a control sample containing a known interrogator gas. The sensor's response profile to this control is established. After exposure to a test sample, the sensor is then exposed again to the known interrogator gas, and a second response profile is determined. A comparison between the test sample response profile and the control profile enables the detection, identification, and quantification of analytes in the test sample.
The problem addressed is that many existing biomarker and analyte detection systems are limited by poor sensitivity and specificity, require bulky or difficult-to-calibrate instrumentation, are incompatible with various sample types, or involve complex, multi-step procedures with numerous reagents. The invention solves this by providing more reproducible and sensitive methods and compositions for analyte detection using gas sensors with functionalized surfaces, enabling simpler detection and quantification.
Key aspects include the use of gas sensors derivatized with analyte binders, which can be biomolecules or other binders tailored for specific analyte interactions. The innovation also permits detection of multiple analytes by employing arrays of gas sensors derivatized with different binders. Detection is achieved by analyzing the differences in gas sensor response profiles during diffusion of an interrogator gas before and after analyte-binding events, allowing indirect detection and quantification in a wide variety of sample types.
Claims Coverage
There are two primary independent inventive features described in the claims: a method for determining the presence of an analyte in a test sample using a gas sensor and a method for detecting the presence of a plurality of analytes with at least two gas sensors.
Method for detecting an analyte using gas sensor response profiles and interrogator gas diffusion
This feature involves: 1. Exposing a gas sensor derivatized with analyte binders to a first gas sample comprising a known interrogator gas and lacking the analyte. 2. Determining a control gas sensor response profile during diffusion of the interrogator gas through the analyte binders and to/from the sensor before and after exposure. 3. Exposing the sensor to a test sample so that analyte-binder complexes form. 4. After terminating test sample exposure, exposing the sensor to a second gas sample with the same interrogator gas and determining a second gas sensor response profile. 5. Comparing the first and second gas sensor response profiles to indicate the presence of the analyte if the diffusion profiles are different after analyte binding compared to the original state. The feature extends to comparing profiles ratiometrically, using biomolecular binders, detecting analytes from biological samples, and quantifying analytes.
Method for detecting a plurality of analytes using sensor arrays functionalized with different binders
This feature includes: - Exposing at least two gas sensors, each derivatized with different analyte binders, to a known interrogator gas and generating distinct response profiles for each sensor. - Exposing the sensors to a test sample under conditions that promote formation of the respective binder-analyte complexes. - Following test sample exposure, re-exposing sensors to the interrogator gas and determining new response profiles. - Comparing corresponding pre- and post-analyte binding response profiles for each sensor to indicate the presence of specific analytes based on observed diffusion differences. The profiles may be stored in a database, used for quantification, and compared using read-out integrated circuits and data analysis algorithms.
In summary, the inventive features define methods for both single and multiple analyte detection using diffusion-based gas sensor response profiling in combination with specific binders and interrogator gases, enabling identification and quantification of analytes through profile comparison.
Stated Advantages
The methods improve sensitivity and specificity in detection of analytes compared to many current detection systems.
Bulkiness and calibration complexity of existing instrumentation are reduced or eliminated.
Compatibility with different types of sample matrices, including biological and environmental samples, is provided.
The process enables reproducible and sensitive quantification of analytes and allows for multiplexed analyte detection using sensor arrays.
Documented Applications
Detection and quantification of chemicals, biomolecules, and other analytes from biological samples.
Detection and quantification from environmental samples, such as air, water, and soil extracts.
Diagnosing disease, monitoring disease progression, detecting pathogens, and genetic profiling.
Evaluation of patients for the presence of disease, disease markers, or therapeutic monitoring.
Analysis of biological threat samples for military or first responders.
Correlating analyte presence or concentration with disease outcome, drug efficacy, or toxicity.
Quality control or monitoring in biological, chemical, industrial, or pharmaceutical manufacturing processes.
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