Bacteriochlorin Derivatives for Multiplex Photoacoustic Imaging
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Solution Overview
Problem
Current photoacoustic imaging (PAI) methods face limitations in simultaneously detecting multiple biomarkers due to broad absorption spectra of existing contrast agents, such as Indocyanine Green, which restricts the ability to distinguish multiple targeted biomarkers within the near-infrared spectral range.
Innovation Solution
Development of synthetic bacteriochlorins and their metallobacteriochlorin derivatives with narrow absorption spectra, allowing for multiplex detection by using multiple agents with non-overlapping absorption peaks within the 650-1070 nm range, and their incorporation into micelles, liposomes, or nanoparticles for enhanced imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of stationary object
If Indocyanine Green is used as a contrast agent, then the imaging depth is improved, but the ability to detect multiple biomarkers simultaneously deteriorates due to broad absorption spectrum
Solution Approach 1:
The patent segments the broad absorption spectrum into multiple narrow, non-overlapping spectral bands by using different bacteriochlorin derivatives (e.g., B1 at 707 nm, B2 at 752 nm, B3 at 806 nm). Each derivative targets a specific spectral region, enabling multiplex detection without spectral overlap while maintaining deep tissue penetration capability
Solution Approach 2:
Each bacteriochlorin derivative is designed with specific local spectral properties (narrow absorption peaks at distinct wavelengths) to optimize its function for detecting particular biomarkers. The derivatives exhibit tailored absorption characteristics that match specific tissue optical windows, allowing simultaneous detection with minimal interference
2Measurement precision
If multiple contrast agents with different absorption spectra are used, then the ability to detect multiple biomarkers is improved, but spectral overlap increases making differentiation difficult
Solution Approach 1:
The patent systematically varies key spectral parameters (peak wavelength, absorption bandwidth) across the bacteriochlorin derivative series. By tuning the molecular structure of each derivative, the patent achieves distinct peak wavelengths (707 nm, 752 nm, 806 nm) with controlled bandwidths that prevent overlap, maximizing spectral information for each biomarker
3Measurement precision
If narrow absorption spectrum contrast agents are used, then multiplex detection capability is improved, but the overall signal intensity may be reduced
Solution Approach 1:
The patent employs composite formulations containing multiple bacteriochlorin derivatives, each optimized for specific spectral regions. The composite system leverages the complementary absorption profiles of individual derivatives to achieve high overall optical efficiency across the broad NIR spectrum while maintaining narrow, non-overlapping peaks for each component
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 the simultaneous detection of multiple biomarkers with minimal spectral overlap, allowing for more complex analyses and deeper tissue imaging compared to conventional methods, with nickel-bacteriochlorin complexes demonstrating a five-fold stronger PAI signal than Indocyanine Green.
Implementation Method 1
Photoacoustic Imaging (PAI) is an emerging medical imaging modality that is based on the phenomenon of conversion of optical energy into acoustic energy
Data Source
AI summary
Provided are photoacoustic imaging contrast agents that include at least one radiation-absorbing component comprising a bacteriochlorin, a metallobacteriochlorin, a derivative thereof, or a combination thereof. Also provided are methods for using the disclosed photoacoustic imaging contrast agents either singly or in combination for generating an image of a volume, optionally a subject or a body part, cell, tissue, or organ thereof. Further provided are compositions and methods for multiplex photoacoustic imaging of a volume, optionally a subject or a body part, cell, tissue, or organ thereof using photoacoustic imaging contrast agents that include a plurality of the presently disclosed bacteriochlorins, metallobacteriochlorins, and/or derivatives thereof simultaneously.