Redox probing for chemical information
Inventors
Kim, Eunkyoung • Payne, Gregory F. • KANG, Mijeong • Ghodssi, Reza • WINKLER, Thomas E. • BANIS, George • Kitchen, Christopher • KELLY, Deanna L. • Bentley, William E.
Assignees
University of Maryland Baltimore • University of Maryland College Park
Publication Number
US-12352720-B2
Publication Date
2025-07-08
Expiration Date
2037-12-04
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Methods are provided that allow global access to redox-based molecular information by coupling electrochemical measurements with signal processing approaches. More specifically, the disclosure provides methods that rely on the use of redox probes to assay samples for redox activities that act to exchange electrons with the probe thereby generating detectable optical and electrochemical signature signals that can then be assigned to a sample feature of interest. In particular embodiments, the disclosed assay methods are useful for diagnosis and prognosis of disorders, such as schizophrenia, that are found to be associated with a specific redox-based signature within a subject sample.
Core Innovation
The invention provides methods that globally access redox-based molecular information by coupling electrochemical measurements with signal processing approaches. The methods utilize redox probes, also termed redox mediators or electron shuttles, to assay samples for redox activities that exchange electrons with the probe. This interaction generates detectable optical and electrochemical signature signals which can be assigned to specific features, traits, or qualities of interest within the sample.
The methods enable dynamic detection of complex redox contexts by applying electrical inputs such as oxidative or reductive pulses or oscillating voltages, thus developing distinctive redox-based signatures over time. The approach is applicable to a wide range of sample types including biological, soil, water, air, chemical, pharmaceutical, agricultural, environmental, and industrial compositions. Particularly, the invention addresses the detection and diagnosis of disorders, like schizophrenia, which are associated with specific redox-based signatures within subject samples.
The problem solved by the invention concerns the limitations of traditional chemically specific analytical methods, such as HPLC and mass spectrometry, which are costly, time-consuming, labor-intensive, and not easily translatable across various fields. There exists a significant challenge in the development of simple, rapid, and objective measurement techniques to assess redox activities within samples, especially biological ones, as aberrant redox chemistry underlies many diseases including cancer, inflammation, cardiovascular disease, neurodegenerative, and neuropsychiatric disorders. This invention provides a robust solution by offering fast, sensitive assays utilizing redox probes coupled with optical and electrochemical detection modalities for improved diagnosis, prognosis, and monitoring.
Claims Coverage
The patent contains multiple independent claims focusing on methods for determining redox-based conditions associated with oxidative stress by using redox-mediators coupled with electrical inputs and measurement of optical and electrochemical signals.
Dynamic redox-based condition determination at point-of-care
A method for determining a redox-based condition associated with oxidative stress by contacting a patient sample with one or more redox-mediators, providing a sequence of oxidative electrical input pulses with varying durations separated by off voltages, measuring dynamic current, charge, and optical outputs over time, and deriving electrochemical or spectroelectrochemical signal signatures to assay for the condition at the point-of-care.
Comparison and analysis of signal signatures
Comparing the derived electrochemical or spectroelectrochemical signal signatures from the patient sample to those of control samples stored in a database, using an identification module programmed to identify executable code of the signatures, and analyzing the comparison results to detect the presence of a marker of interest within the sample.
Training and autonomous adjustment of analyzer
Training the analyzer to identify and correlate signature patterns that discriminate between sample and control datasets, and autonomously adjusting the electrical input to generate signal signatures with enhanced discriminating capabilities.
Use of biological samples including serum
Employing biological samples derived from the patient, including blood, sweat, urine, saliva, or specifically serum samples, in the redox probing and measurement methods.
Treatment adjustment based on redox-based condition detection
Adjusting patient treatment based on the determined presence of the redox-based condition.
Association of redox-based conditions with oxidative stress disorders
Focusing on redox-based conditions associated with oxidative stress disorders, redox dysregulation, inflammation, and specifically schizophrenia.
Selection of redox-mediators
Using redox-mediators selected from metals such as iridium, ferrocene, ferricyanide, ruthenium, osmium, rhodium, copper, cobalt, nickel, chromium, platinum, palladium, redox-active organic molecules, and radical precursors; specifically including iridium salts such as K2IrCl6 (IrOX).
Sequence of oxidative and reductive electrical pulses for detection
Using an electrical input sequence comprising oxidative and reductive pulses with specifically defined voltages and durations that bracket the redox potential of the mediators to derive multiple quantitative signal metrics from simultaneous electrode and optical measurements over time.
Three pulse-redox-relaxation electrical input sequence for serum assay
Implementing a three pulse-redox-relaxation sequence electrical input to a diluted serum sample containing an iridium-based redox mediator, capturing optical and electrical signals as redox-state-dependent responses, and extracting multiple quantitative metrics including charge transferred, optical absorbance, cross-modal responses, decay constants, and charge ratios to access global chemical information on oxidative stress at the point-of-care.
The claims collectively cover methods and systems for redox probing using redox-mediators and dynamic electrical inputs to generate optical and electrochemical signatures for detecting oxidative stress-related conditions, including schizophrenia, and for monitoring treatment responses. The claims emphasize use of specific redox-mediators such as iridium salts, sample types including serum, measurement at the point-of-care, and signal processing for pattern identification and discrimination.
Stated Advantages
The methods provide simple, rapid, robust, and non-chemically specific assays for global assessment of redox activity, enabling fast and convenient detection of oxidative stress-related conditions.
The use of iridium-based redox-mediators, especially K2IrCl6 (IrOX), offers high sensitivity to biologically relevant reductants such as glutathione (GSH), improving detection capabilities compared to existing assays.
The combined optical and electrochemical detection modalities enable corroborative and sensitive measurement, enhancing assay reliability and enabling dynamic monitoring through electrical input stimuli.
The methods can discriminate between healthy and diseased samples, such as distinguishing schizophrenia patients from healthy controls with statistically significant accuracy, and correlate with disease severity.
Assay formats are compatible with point-of-care testing using inexpensive, portable screen-printed electrodes and microplate readers, facilitating clinical applicability and timely diagnosis.
The approach allows for monitoring of treatment response by assessing changes in redox-based signatures, supporting personalized patient management.
Documented Applications
Diagnosis, prognosis, and monitoring of diseases and disorders associated with redox dysfunction and oxidative stress including schizophrenia, cancer, inflammation, cardiovascular disease, neurodegenerative and neuropsychiatric diseases.
Assaying biological samples such as blood, sweat, urine, saliva, and specifically serum samples for redox-based chemical signatures indicative of disease states.
Environmental and industrial analysis including assays of soil, water, air, chemical, pharmaceutical, agricultural, environmental and industrial compositions for detection of contaminants or chemical qualities.
Use of spectroelectrochemical cells and signal processing methods to discover redox-based patterns and signatures correlated to specific sample features, traits, or conditions.
Point-of-care clinical testing enabling rapid assessment of oxidative stress status and objective measurement to complement subjective clinical evaluations.
Development and use of assay kits comprising redox-mediators, electrical input devices, and instructions for detecting redox-based signatures associated with health conditions such as schizophrenia.
Interested in licensing this patent?