No-Reference Slope Spectroscopy for Concentrated Sample Analysis

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing ultraviolet (UV)/visible spectrophotometers face challenges in accurately determining the concentration of highly concentrated biological samples like proteins, DNA, or RNA, often requiring dilution and multiple measurements, which introduces errors and occupies significant space with bulky instrumentation.

Innovation Solution

A variable path length spectroscopy system using a compact light source and a movable probe to dynamically change the path length during absorbance measurement, allowing concentration determination without requiring knowledge of the path length, and optionally employing a 'no-reference signal' mode to streamline measurements by omitting incident intensity measurements when the light source is stable.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If standard cuvettes with fixed path length are used, then the measurement system is simple, but accurate concentration measurement of highly concentrated samples is difficult without dilution

Engineering Contradiction:
Improveconcentration measurement accuracyVSAvoidmeasurement system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent employs a movable probe that dynamically adjusts the path length through the sample during measurement. The probe can be positioned at multiple locations along the sample chamber, allowing the path length to be varied continuously or in steps. This dynamic adjustment enables accurate measurement of highly concentrated samples by optimizing the path length to keep absorbance within the linear range of the detector, eliminating the need for sample dilution while maintaining measurement simplicity.

Inventive Principle:
Principle #15Dynamics

2Measurement precision

If multiple dilutions are performed to measure concentrated samples, then concentration can be measured within linear range, but dilution errors and sample loss occur

Engineering Contradiction:
Improveconcentration measurement accuracyVSAvoidsample loss
Core Design Contradiction:
Measurement precisionVSLoss of substance

Solution Approach 1:

Instead of requiring multiple dilutions, the patent uses a single sample chamber with a movable probe that dynamically adjusts path length. The probe can be repositioned to achieve the optimal path length for measuring highly concentrated samples directly, eliminating the need for dilution steps and associated errors while preserving the entire sample for downstream applications.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the measurement parameter from fixed path length to variable path length. By adjusting the path length parameter dynamically during measurement, the system can accommodate a wide range of concentrations without requiring sample dilution, thereby avoiding dilution errors and sample loss while maintaining measurement accuracy.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If variable path length spectroscopy is implemented, then concentrated samples can be measured without dilution, but the instrumentation requires extensive installation effort and space

Engineering Contradiction:
Improveconcentration measurement accuracyVSAvoidinstrumentation space
Core Design Contradiction:
Measurement precisionVSArea of stationary object

Solution Approach 1:

The patent segments the path length adjustment function into a separate movable probe component that can be independently positioned within the sample chamber. This segmentation allows the path length to be varied without requiring a complete redesign of the entire instrument, reducing installation complexity and space requirements while maintaining the ability to measure concentrated samples accurately.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The movable probe acts as an intermediary element that mediates between the light source and the sample. By introducing this intermediate component, the system achieves variable path length capability without requiring a complete redesign of the optical path or the entire instrument structure, thereby reducing installation effort and space requirements.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Measurement precision

If multiple intensity measurements are taken for each sample at a given path length, then accurate absorbance determination can be made, but measurement time increases

Engineering Contradiction:
Improveabsorbance determination accuracyVSAvoidmeasurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent uses dynamic path length adjustment to obtain multiple intensity measurements at different path lengths in a single continuous measurement sequence. The movable probe can be repositioned during the measurement process, allowing the system to collect data points at varying path lengths without requiring separate measurement cycles, thereby reducing total measurement time while maintaining accuracy.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent maintains continuous useful action by performing path length adjustments and intensity measurements in an uninterrupted sequence. The movable probe can be repositioned and measurements taken without requiring the system to stop or reset between different path length measurements, ensuring continuous data collection and reducing overall measurement time while preserving accuracy.

Inventive Principle:
Principle #20Continuity of useful action

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

Enables accurate and rapid concentration measurement of fluid samples with reduced space requirements and fewer measurements, improving flexibility and accuracy by directly determining concentration based on path length variations and intensity changes.

Implementation Method 1

Absorption spectroscopy is used to measure composition and/or properties of a material in any phase, gas, liquid, solid. For example, the optical absorption spectra of liquid substances may be measured to determine concentration or other properties of a species of interest, within a liquid medium.

Methodology Applied
Scientific EffectAbsorption spectroscopy: Absorption Spectroscopy

Implementation Method 2

For a sample consisting of a single homogeneous substance having a concentration c, the light transmitted through the sample will follow a relationship know as Beer's Law: A=εCL where A is the absorbance (also known as the optical density (OD) of the sample at wavelength λ

Methodology Applied
Scientific EffectBeer's Law: Absorption (EM radiation)

Data Source

PatentUS12411043B2No-ref-signal slope spectroscopic measurement
Publication Date: 2025.09.09 REPLIGEN CORP
  • US12411043B2 patent drawing
  • US12411043B2 patent drawing
  • US12411043B2 patent drawing

AI summary

A method includes determining whether a variation in probe radiation intensity meets a stability criterion; directing the probe radiation through a probe, when the probe is disposed at a first position, defining a first path length L1 of the probe radiation through the fluid sample; measuring a transmitted intensity I1 of the probe radiation after passing through the fluid sample when the probe is disposed at the first position; directing the probe radiation through the probe when the probe is disposed at a second position, defining a second path length L2 of the probe radiation through the fluid sample; measuring a transmitted intensity I2 of the probe radiation after passing through the fluid sample when the probe is disposed at the second position; and determining a concentration C of a material in the fluid sample based upon L1, I1, L2, and I2, when the stability criterion is met.