Internal-Standard Sample Dispenser for Sub-Microliter Quantitation

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Solution Overview

Problem

Current methods for introducing internal standards in quantitative analysis of small volumes, such as those used in ambient ionization methods, face challenges with accuracy due to high error rates in pipetting sub-microliter liquids, particularly in complex samples like blood, leading to ion suppression and compromised detection of analytes.

Innovation Solution

A fluid dispenser with a fluid chamber coated with internal standard on its inner surface ensures precise mixing of the internal standard with the sample, regulating both volumes and improving quantitation accuracy, utilizing pneumatic pressure control and capillary action for efficient sample handling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If air displacement pipette is used to transport sub-microliter liquid, then internal standard can be introduced to sample, but pipetting accuracy deteriorates with 12% error

Engineering Contradiction:
Improvequantitation accuracyVSAvoidpipetting accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The invention extracts the internal standard introduction step from manual pipetting and integrates it into the ambient ionization device itself. The device incorporates an internal standard solution reservoir and delivery mechanism that automatically introduces the internal standard directly at the analysis site, eliminating the need for separate pipetting operations and their associated errors.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention merges the internal standard introduction function with the ambient ionization analysis device. The device combines sample introduction, internal standard addition, and ionization capabilities into a single integrated system, allowing simultaneous or sequential introduction of both sample and internal standard without requiring separate pipetting steps.

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If internal standard is spiked into samples using pipetting and vortex mixing, then calibration can be performed, but the method becomes unsuitable for microliter samples and increases operation complexity

Engineering Contradiction:
Improvequantitation accuracyVSAvoidoperation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The device performs self-service by automatically introducing and mixing the internal standard without requiring manual pipetting or vortex mixing operations. The integrated system handles internal standard delivery and sample mixing through its own built-in mechanisms, eliminating the need for operators to perform complex manual mixing procedures.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The ambient ionization device is designed with multi-functionality, serving both as the analysis instrument and as the internal standard introduction device. This universal design allows the same device to perform sample introduction, internal standard addition, and ionization, simplifying the overall workflow while maintaining quantitation accuracy.

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

3Productivity

If ambient ionization methods are used for quantitative analysis, then sample preparation time is reduced, but ion suppression occurs due to interfering chemicals in complex samples

Engineering Contradiction:
Improveanalysis speedVSAvoiddetection sensitivity
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The internal standard acts as an intermediary that compensates for ion suppression effects in complex samples. By introducing a known amount of internal standard that experiences the same matrix effects as the analyte, the system can correct for signal suppression and maintain accurate quantitation even in the presence of interfering chemicals.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

The solution significantly enhances quantitation accuracy for trace compounds in small volumes, reducing errors and matrix effects, enabling reliable analysis of complex mixtures without the need for extensive sample preparation.

Implementation Method 1

Fluid containing the analytes that is taken into the chamber mixes with the internal standard

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Implementation Method 2

utilizing pneumatic pressure control and capillary action for efficient sample handling

Methodology Applied
Scientific EffectPneumatic pressure: Pressurisation

Data Source

PatentUS11867684B2Sample dispenser including an internal standard and methods of use thereof
Publication Date: 2024.01.09 PURDUE RES FOUND
  • US11867684B2 patent drawing
  • US11867684B2 patent drawing
  • US11867684B2 patent drawing

AI summary

The invention generally relates to a sample dispenser including an internal standard and methods of use thereof.