Mono-nitro-BAPTA Chelator for Selective Calcium Measurement

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Solution Overview

Problem

Current methods for measuring calcium and magnesium levels in biological samples are inconvenient, requiring expensive instrumentation and skilled operators, and often interfere with each other's quantification, making it difficult to accurately distinguish between slight deviations in calcium levels which are crucial for diagnosing conditions like hyperparathyroidism and hypoparathyroidism.

Innovation Solution

The use of mono-nitro-derivatives of BAPTA-type chelators that are stable, non-toxic, and do not bind to magnesium or other metal ions, allowing for precise calcium measurement over a broad range without interference, using a method that involves binding calcium ions to the chelator, releasing them, and measuring the change in absorbance to determine concentration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If atomic absorption is used for measuring calcium and magnesium, then measurement precision is improved, but device complexity and operational difficulty increase

Engineering Contradiction:
Improvecalcium and magnesium measurement precisionVSAvoidinstrumentation complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the complex atomic absorption instrumentation with a simpler colorimetric measurement system. The method uses a chelator that forms a colored complex with calcium ions, allowing measurement through absorbance spectroscopy rather than requiring complex atomic absorption equipment. This substitution maintains measurement precision while significantly reducing device complexity and operational difficulty.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the measurement parameter from atomic absorption to colorimetric absorbance. By using a chelator that binds calcium ions and produces a measurable color change or absorbance signal, the method transforms the measurement into a simpler optical parameter that can be measured with standard spectrophotometers, avoiding the need for expensive atomic absorption instrumentation.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If atomic absorption is used for measuring calcium and magnesium, then measurement precision is improved, but ease of operation deteriorates

Engineering Contradiction:
Improvecalcium and magnesium measurement precisionVSAvoidoperational ease
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces the complex atomic absorption instrumentation with a simpler colorimetric measurement system. The method uses a chelator that forms a colored complex with calcium ions, allowing measurement through absorbance spectroscopy rather than requiring complex atomic absorption equipment. This substitution maintains measurement precision while significantly reducing device complexity and operational difficulty.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The chelator-based method is designed to be self-contained and straightforward. The reagent automatically binds calcium ions and produces a measurable signal without requiring complex sample preparation or specialized operational skills. The procedure simplifies the measurement process to basic mixing and reading absorbance, making it easily operable by routine laboratory personnel.

Inventive Principle:
Principle #25Self-service

3Productivity

If conventional chelators are used for calcium measurement, then measurement speed is improved, but measurement precision deteriorates due to interference from magnesium and other ions

Engineering Contradiction:
Improvemeasurement speedVSAvoidcalcium measurement precision
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent modifies the chelator structure with specific substituents (such as nitro groups at defined positions) to create a variant that has selective affinity for calcium ions over magnesium and other metal ions. This local modification of the chelator's chemical properties allows it to distinguish between calcium and magnesium, maintaining fast measurement speed while improving precision by eliminating interference from other ions.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses modified BAPTA-type chelators with specific substituent patterns (e.g., mono-nitro derivatives) that create a composite molecular structure with selective binding properties. These modified chelators maintain the rapid binding kinetics needed for high throughput while adding specificity to distinguish calcium from magnesium and other metal ions, thus improving measurement precision without sacrificing speed.

Inventive Principle:
Principle #40Composite materials

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

This approach provides a stable, accurate, and efficient method for measuring calcium ions in clinical samples, reducing the need for expensive equipment and skilled operators, while avoiding interference from magnesium or other ions, thus enabling precise diagnostics.

Implementation Method 1

mixing the sample with a solution comprising a mono-nitro-BAPTA-type chelator thereby binding calcium ions to the mono-nitro-BAPTA-type chelator

Methodology Applied
Scientific EffectChelation:

Implementation Method 2

releasing calcium ions from the mono-nitro-BAPTA-type chelator, wherein said release causes a change in absorbance of the mono-nitro-BAPTA-type chelator, measuring the change in absorbance

Methodology Applied
Scientific EffectAbsorbance measurement: Absorption Spectroscopy

Data Source

PatentUS8962338B2Methods for measurement of calcium ions
Publication Date: 2015.02.24 ROCHE DIAGNOSTICS OPERATIONS INC
  • US8962338B2 patent drawing
  • US8962338B2 patent drawing
  • US8962338B2 patent drawing

AI summary

Reagents and methods for determination of calcium within a sample. Specific embodiments include a reagent for determination of calcium comprising a mono-nitro substituted BAPTA-type chelator (BAPTA=1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid). Methods for accurate determination of calcium in a sample, such as a blood, whole blood, plasma or serum or any other aqueous liquid sample including cerebrospinal fluid, lymph, salivary juice or urine. Embodiments are also useful for clinical diagnoses.