Graded Bioprocess Monitoring via Referenced Optical Measurement

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Solution Overview

Problem

Current bioprocessing techniques face challenges in measuring biochemical constituents due to sensitivity and specificity issues in optical measurements, with background variations and noise from media conditions, leading to inaccurate readings of target analytes in bioreactors.

Innovation Solution

The implementation of a system that uses a combined flow of active and fresh media in a confined region, allowing for time- and spatially-resolved referenced optical measurements under identical conditions, reducing background effects and enabling high-frequency differential measurements of bioprocess constituents like cells, nutrients, and waste products.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If spectroscopic analytical techniques are used to measure biochemical constituents, then rich information on media state and cell constituents can be obtained, but background variations and noise from media conditions cause measurement inaccuracies

Engineering Contradiction:
Improveinformation on biochemical stateVSAvoidmeasurement accuracy
Core Design Contradiction:
Loss of informationVSMeasurement precision

Solution Approach 1:

The patent introduces a reference media stream as an intermediary element that experiences identical environmental conditions and optical path variations as the active media. By measuring both streams simultaneously and comparing their differences, the system isolates the biochemical signal from background noise caused by temperature fluctuations, humidity changes, and optical component drift.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent extracts the background signal by measuring a reference media stream that contains all environmental and instrumental variations except the biochemical constituents of interest. This extracted reference signal is then subtracted from the active media measurement, leaving only the pure biochemical information.

Inventive Principle:
Principle #2Taking out (Extraction)

2Measurement precision

If vibrational spectral measurements are performed, then biochemical constituents can be detected, but the weak signals suffer from significant background variations

Engineering Contradiction:
Improvedetection capabilityVSAvoidbackground variations
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The reference media stream serves as a mediator that experiences all environmental disturbances (temperature, humidity, optical path changes) but lacks the biochemical constituents. By comparing the active media signal against this intermediary reference, the system cancels out the harmful background variations while preserving the weak vibrational spectral signals.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The system continuously monitors the reference media stream and uses this feedback to dynamically correct measurements of the active media in real-time, compensating for drifting baseline signals and environmental variations that would otherwise swamp the weak vibrational signals.

Inventive Principle:
Principle #23Feedback

3Productivity

If optical measurements are performed in bioprocess systems, then real-time monitoring is achieved, but contamination risks and background noise increase

Engineering Contradiction:
Improvereal-time monitoring capabilityVSAvoidcontamination and noise
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the optical measurement system into two independent but parallel channels: one measuring active media and another measuring reference media. This segmentation allows each channel to be optimized independently and enables mathematical separation of the biochemical signal from background noise through differential analysis.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The reference media acts as an intermediary control that flows through an identical optical path and experiences the same environmental conditions, providing a real-time baseline that subtracts out contamination and background noise from the active media measurements.

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

This approach significantly enhances the sensitivity and accuracy of bioprocess constituent measurements by minimizing background noise and allowing for real-time, in-line monitoring of changes in bioreactor compositions, improving signal-to-noise ratios and reducing contamination risks.

Implementation Method 1

measuring a difference in optical characteristics between the at least two differently-filtered streams

Methodology Applied
Scientific EffectAbsorption: Absorption (EM radiation)

Implementation Method 2

measuring a difference in optical characteristics between the at least two differently-filtered streams

Methodology Applied
Scientific EffectScattering: Scattering

Implementation Method 3

measuring a difference in optical characteristics between the at least two differently-filtered streams

Methodology Applied
Scientific EffectRaman scattering:

Implementation Method 4

relative pressures of the two fluids at the distinct boundary moves the distinct boundary orthogonal to a direction of the laminar flow at a media-dependent frequency

Methodology Applied
Scientific EffectVortex shedding: Kármán Vortex Street

Implementation Method 5

The fluid combiner combines the at least two differently-filtered streams into a flow chamber including an optical interrogation region

Methodology Applied
Scientific EffectLaminar flow: Laminar Flow

Data Source

PatentUS20240060031A1Graded Bioprocess Monitoring
Publication Date: 2024.02.22 1087 SYST
  • US20240060031A1 patent drawing
  • US20240060031A1 patent drawing
  • US20240060031A1 patent drawing

AI summary

Combining through self-modulation a flow of active media from a working vessel of a bioprocess together with a flow of reference media and making a time- and/or spatially-resolved referenced optical measurement of the active vs reference media in a confined flow region and time, such that the two liquids are measured in substantially identical conditions.