Dual-Wavelength IRIS Biomolecular Analysis Bulk Effect Minimization
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Solution Overview
Problem
Label-free optical biosensors face challenges in detecting small molecular weight targets due to high background noise and bulk effects, which complicate the measurement of molecular binding kinetics and limit the flexibility of target solution composition.
Innovation Solution
The use of Interferometric Reflectance Imaging Sensors (IRIS) with dual illumination sources of different wavelengths to minimize bulk effects, allowing for the separation of surface binding and solution refractive index changes, enabling accurate small molecule affinity measurements by adjusting the weighted spectrum of combined light to coincide with the bulk effect minimization wavelength.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If label-free optical biosensors are used to detect biomarkers, then highly sensitive and multiplexed detection is achieved, but bulk effects from solution composition changes create high background noise that complicates measurement
Solution Approach 1:
The patent segments the optical detection into two independent channels: a measurement channel that detects both surface binding and bulk refractive index changes, and a reference channel that detects only bulk refractive index changes. By subtracting the reference channel signal from the measurement channel signal, the bulk effect is eliminated and only the surface binding signal remains. This segmentation allows simultaneous detection of biomarkers with high sensitivity while eliminating the harmful bulk effect noise.
Solution Approach 2:
The patent introduces a reference channel as an intermediary that experiences the same bulk refractive index changes as the measurement channel but without surface binding events. This reference channel acts as a mediator that captures and transmits the bulk effect information, which is then subtracted from the measurement channel to isolate the true surface binding signal, thereby eliminating bulk effect noise while preserving detection sensitivity.
2Object-affected harmful factors
If refractive index matching is performed to eliminate bulk effects, then background noise is reduced, but the ability to detect small molecular weight targets with low signals is compromised
Solution Approach 1:
The patent segments the detection into measurement and reference channels, allowing the measurement channel to maintain high sensitivity for small molecule detection while the reference channel captures bulk effects for subtraction. This segmentation enables simultaneous optimization of both noise reduction and small molecule detection capability, as the measurement channel does not require refractive index matching that would compromise sensitivity.
Solution Approach 2:
The patent changes the detection parameter from direct refractive index measurement to differential reflectance measurement between two channels. By measuring the difference in reflectance signals between the measurement channel (with surface binding) and reference channel (without surface binding), the system achieves both bulk effect elimination and maintained sensitivity for small molecule detection, avoiding the need for refractive index matching.
3Measurement precision
If dual illumination sources with different wavelengths are used, then bulk effects are minimized and surface binding is separated from solution refractive index changes, but device complexity increases
Solution Approach 1:
The patent segments the illumination system into two independent light sources with different wavelengths, each illuminating the sample through the same optical path. This segmentation allows wavelength-dependent differential measurement where the first wavelength is more sensitive to surface binding and the second wavelength is more sensitive to bulk refractive index changes. The segmented approach achieves high measurement precision while keeping each illumination source relatively simple.
Solution Approach 2:
The patent makes the optical path universal by using the same optical components and detection path for both wavelength sources. The beam combiner and detector serve multiple functions by handling both wavelengths simultaneously, reducing overall device complexity despite using dual illumination sources. This multi-functional design allows the system to achieve wavelength-dependent differential measurement without proportionally increasing complexity.
4Adaptability or versatility
If additives are added to target solutions to improve solubility of small molecules, then solution composition flexibility is improved, but refractive index changes introduce bulk effects that interfere with measurement
Solution Approach 1:
The patent introduces a reference channel as an intermediary that experiences the same refractive index changes from solution additives as the measurement channel. By subtracting the reference channel signal from the measurement channel signal, the bulk refractive index effects from additives are eliminated, allowing flexible solution composition with additives like DMSO without interference in the final binding measurement.
Solution Approach 2:
The patent extracts the bulk refractive index effect from the total signal by using the reference channel to capture and isolate the bulk effect component. Through differential measurement, the bulk effect is taken out and removed from the measurement, leaving only the surface binding signal. This allows additive-containing solutions to be used with full flexibility while eliminating their refractive index interference.
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 reduces noise and allows for precise characterization of small molecule binding kinetics, enhancing the sensitivity and flexibility of biomolecular analysis by eliminating the bulk effect, thereby improving the accuracy of molecular binding affinity measurements.
Implementation Method 1
The sensor substrate includes two or more dielectric layers such that the imaging system is configured for common path interferometry
Implementation Method 2
reflecting incident light of the combined light from the sensor substrate to produce a signal
Data Source
AI summary
An apparatus, and method of operating the same, detects changes in biomass accumulating on a surface of a substrate while minimizing bulk effect. The apparatus includes a sensor substrate and two illumination sources. A first illumination source generates a first light having a first central wavelength. A second illumination source generates a second light having a second central wavelength different than the first wavelength. The first and second light are mixed to produce a combined light. An analyte solution is introduced to the sensor substrate. Incident light of the combined light is reflected from the sensor substrate to produce a signal. The signal is imaged with a camera to obtain a reflectance. Reflectance produced by the combined light is not affected by variations in the dielectric properties of the analyte solution. A biomass accumulated on the substrate is computed based on the reflectance.