Cyclic Square Wave Voltammetry for Tonic Dopamine Measurement

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Solution Overview

Problem

Current fast-scan cyclic voltammetry techniques are limited to measuring rapid changes in dopamine release and cannot effectively quantify slower, tonic extracellular dopamine levels due to their differential method nature, which is essential for understanding various neurological and psychiatric diseases.

Innovation Solution

The application of multiple cyclic square wave voltammetry (M-CSWV) with a delayed holding potential period to control dopamine adsorption on carbon fiber microelectrodes, allowing for the measurement of tonic dopamine concentrations by sampling and subtracting background currents, and using dynamic background subtraction and capacitive background current simulation to eliminate capacitive interference.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If conventional fast-scan cyclic voltammetry (FSCV) is used to measure dopamine release, then rapid phasic changes can be detected, but slower tonic extracellular dopamine levels cannot be effectively quantified

Engineering Contradiction:
Improvetemporal resolution for phasic dopamine detectionVSAvoidquantification of tonic dopamine levels
Core Design Contradiction:
SpeedVSMeasurement precision

Solution Approach 1:

The voltammetric waveform is segmented into multiple cyclic square wave components with different durations. Shorter cycles capture rapid phasic dopamine release, while longer cycles enable measurement of slower tonic dopamine levels. This segmentation allows the system to resolve both fast and slow dopamine dynamics simultaneously by analyzing different temporal segments of the waveform response.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the temporal parameters of the voltammetric waveform by using multiple cyclic square wave durations rather than a single fixed cycle time. By varying the cycle duration parameter across multiple cycles, the system can probe different temporal scales of dopamine release, enabling detection of both phasic (rapid) and tonic (slow) dopamine levels with appropriate precision.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If multiple cyclic square wave voltammetry is applied to measure tonic dopamine levels, then measurement precision improves, but device complexity increases due to multiple waveform parameters

Engineering Contradiction:
Improvequantification of tonic dopamine concentrationsVSAvoidwaveform generation and control system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The multiple cyclic square wave voltammetry waveform serves multiple functions: it detects both phasic and tonic dopamine release, provides temporal resolution across different scales, and enables concentration quantification. This multi-functional waveform design allows a single measurement system to perform what would otherwise require multiple separate measurement protocols, reducing overall system complexity despite the sophisticated waveform structure.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The measurement system uses periodic cyclic square wave waveforms with varying durations repeated in a systematic sequence. This periodic action allows the system to cycle through different measurement regimes (fast and slow time scales) in a regular pattern, making the complex multi-parameter measurement process manageable and systematic rather than requiring continuous adjustment of multiple independent parameters.

Inventive Principle:
Principle #19Periodic action

3Loss of information

If conventional FSCV differential method is used, then phasic dopamine changes are detected, but background subtraction removes tonic dopamine information

Engineering Contradiction:
Improvepreservation of tonic dopamine signalVSAvoidcapacitive background current interference
Core Design Contradiction:
Loss of informationVSObject-generated harmful factors

Solution Approach 1:

The invention extracts tonic dopamine information by separating it from the background current through analysis of the multiple cyclic square wave responses. By taking out and analyzing the contribution of each cycle duration, the system can isolate the tonic dopamine signal that would otherwise be lost in the background subtraction process, while still removing capacitive interference through appropriate reference measurements.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The system uses multiple copies of the cyclic square wave waveform with different durations to create redundant measurements. By comparing these copied waveforms, the system can identify and remove capacitive background currents that appear consistently across all cycles, while preserving the tonic dopamine signal that manifests differently across the various cycle durations.

Inventive Principle:
Principle #26Copying

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

M-CSWV provides high temporal resolution and sensitivity in measuring tonic dopamine levels, enabling more accurate monitoring of basal concentrations and allowing for closed-loop feedback systems for neural stimulation adjustments, thereby improving the understanding and management of dopamine-related diseases.

Implementation Method 1

measuring an electrical current response to the electrical stimulus using the electrode that is located in the solution

Methodology Applied
Scientific EffectElectrochemical oxidation: Oxidation

Implementation Method 2

the M-CSW signal comprises a square wave oscillation superimposed on a staircase waveform

Methodology Applied
Scientific EffectElectrical signal generation:

Implementation Method 3

M-CSWV can be applied in conjunction with a delayed holding potential period to control dopamine adsorption to the carbon fiber microelectrode (CFM) surface

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentEP3841378B1Measuring neurochemical levels with multiple cyclic square wave voltammetry
Publication Date: 2024.01.03 MAYO FOUNDATION FOR MEDICAL EDUCATION & RESEARCH
  • EP3841378B1 patent drawingFigure 1A~1C
  • EP3841378B1 patent drawingFigure 2A~2C
  • EP3841378B1 patent drawingFigure 2D~2E

AI summary

Systems, methods, and devices for generating multiple cyclic square-waveforms and sloped-edge square waveforms. Aspects of the techniques disclosed herein include applying the generated waveforms to an electrode used in voltammetry, e.g., to measure a level of a neurochemical in neural tissue. An electrode can be located in a solution, and an electrical stimulus applied to the solution through the electrode using a multiple cyclic square waveform. An electrical current response to the stimulus is measured, and a level of an analyte (e.g., dopamine or other neurochemical(s)) determined based on the electrical current response.