Methods for detecting and quantifying analytes using ionic species diffusion
Inventors
Savoy, Steve M. • Hoover, Kyle W. • Mann, Chris W. • Mitchell, Daniel R. • John, Jeremy J. • Greis, Alexander P.
Assignees
Publication Number
US-10386365-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 an ion sensor to a control sample of a known interrogator ion is determined. The ion sensor is exposed to a test sample then to a second sample comprising the known interrogator ion, and a test sample response profile of the ion 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 detecting and quantifying one or more analytes in a test sample using ion sensors. A response profile of the ion sensor to a control sample of a known interrogator ion is determined. The sensor is then exposed to a test sample, followed by exposure to a second sample containing the known interrogator ion. The resulting test sensor response profile is compared to the control sensor response profile to detect, identify, and quantify analytes in the test sample.
The problem addressed by the invention is the complexity, limited sensitivity and specificity, and lack of reproducibility in conventional analyte detection and quantification systems such as fluorescence labeling, PCR, and microarrays. The present invention provides simpler, reproducible, and more sensitive detection and quantification through an indirect method based on ionic species diffusion and sensor response differentials.
In the invention, analytes are detected via interaction with specific binders on the sensor surface, forming binder-analyte complexes. The method includes exposing the ion sensor to control and test samples, determining respective response profiles, and performing ratiometric or other comparative analysis. Arrays of sensors with various binders enable multiplexed detection. Materials such as conductometric semiconducting metal oxide nanosensors and porous matrices or membranes can be used to facilitate analyte-specific interactions and enhance sensitivity.
Claims Coverage
There are two independent inventive features covered by the independent claims.
Method for determining presence of an analyte using sensor response profiles to ionic diffusion
This inventive feature covers a method that includes: 1. Exposing an ion sensor derivatized with analyte-specific binders to a first liquid ionic solution containing a known interrogator ion species and lacking the analyte. 2. Stopping this exposure and determining a first ion sensor response profile during diffusion of the interrogator ion. 3. Exposing the sensor to the test sample under conditions permitting binder-analyte complex formation, then terminating test sample exposure. 4. Exposing the sensor to a second liquid ionic solution with the known interrogator ion species, determining a second ion sensor response profile during diffusion. 5. Indicating the presence of analyte by comparing the first and second ion sensor response profiles and detecting a difference in diffusion attributed to formation of binder-analyte complexes.
Method for detecting presence of multiple analytes using multiple sensors with analyte-specific binders and comparative response profiles
This inventive feature encompasses a method involving: - Using at least a first and a second ion sensor, each derivatized with binders specific for different analytes. - Exposing both sensors to a first liquid ionic solution sample with known interrogator ion species, which lacks the analytes of interest, and determining individual sensor response profiles for each. - Exposing both sensors to a test sample for binder-analyte complex formation, then terminating the exposure. - Exposing both sensors to a second liquid ionic solution with the interrogator ion species and determining third and fourth response profiles. - Indicating the presence of each analyte in the test sample based on differences between the respective pairs of response profiles for each sensor.
The independent claims are directed to methods for detecting and quantifying analytes through comparative analysis of ion sensor response profiles after exposure to control and test samples, optionally enabling multiplex detection with arrays of analyte-specific sensors.
Stated Advantages
The methods enable indirect, reproducible, and sensitive quantification of one or more analytes in a test sample.
High surface area-to-volume nanosensor dimensions permit rapid interfacial ion exchange, facilitating rapid collection of ion sensor response profiles.
High surface area-to-volume dimensions can eliminate the need for repeated heat cycling, reducing calibration degradation and avoiding thermal degradation of biomolecules.
Documented Applications
Detecting the presence of and quantifying chemicals, biomolecules, and other analytes from biological samples.
Analyzing biological samples for biomarker and bioanalyte detection and quantification, useful for diagnosing disease, monitoring disease progression, detecting pathogens, and genetic profiling.
Analyzing extracts of environmental samples, including air, water, and soil, for chemical analytes, toxins, or toxicants.
Evaluating biological samples such as blood, serum, plasma, tissue, semen, saliva, breath, tears, sputum, feces, urine, hair follicles, skin, or any sample containing or constituting biological cells.
Assessing biological samples from patients for disease diagnostics, treatment evaluation, and clinical trial suitability.
Evaluating and correlating analyte presence or concentration in biological samples to pharmacokinetics, drug efficacy, or drug toxicity.
Multiplexed analysis of multiple analytes in a single sample using arrays of sensors with different binders.
Detection of analytes in synthetically prepared biological or chemical samples, which may be precursors or products of biological, chemical, or industrial processes.
Analyzing samples collected as biological threats by military or first responders.
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