Bioluminescent Indicator Sensor for Deep Tissue Imaging
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Solution Overview
Problem
Current optical biosensors rely on fluorescence, which requires an excitation light source, limiting depth of tissue imaging and causing heating and autofluorescence issues, necessitating the development of bioluminescent indicators that eliminate these problems.
Innovation Solution
A bioluminescent indicator comprising a first and third domain of a bioluminescent peptide split by a binding peptide domain that undergoes a conformational change upon ligand binding, bringing the domains into proximity to induce bioluminescence, eliminating the need for an excitation light source.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescence imaging is used, then signal detection is enabled, but excitation light source is required causing tissue scattering and heating
Solution Approach 1:
The patent replaces the mechanical/optical excitation light source system with a biochemical luminescence system. The bioluminescent indicator uses a luciferase enzyme that catalyzes oxidation of luciferin substrate to produce light directly, eliminating the need for external excitation light sources that cause tissue scattering and heating.
Solution Approach 2:
The bioluminescent indicator is self-activating through the enzymatic reaction between luciferase and luciferin substrate. The system serves itself by using metabolic substrates naturally present in cells, eliminating dependence on external illumination equipment.
2Measurement precision
If fluorescence imaging is used, then signal detection is enabled, but autofluorescence from illumination sources reduces signal-to-noise ratio
Solution Approach 1:
The patent substitutes the fluorescence emission mechanism with bioluminescence emission. The luciferase-catalyzed oxidation of luciferin produces light directly without requiring excitation, thereby eliminating autofluorescence background noise from illumination sources and improving signal-to-noise ratio.
3Illumination intensity
If excitation light source is used for fluorescence imaging, then fluorescent reporters can be excited, but imaging depth through tissue is limited
Solution Approach 1:
The patent replaces the excitation light source requirement with a self-emitting bioluminescence system. The luciferase-luciferin reaction generates light intrinsically within the tissue, allowing imaging deeper through tissue without the scattering and absorption limitations that constrain excitation light penetration.
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 deeper tissue imaging with enhanced signal detection and higher signal-to-noise ratio, allowing for non-invasive recording and modulation of neuronal populations without implanted hardware, improving upon the limitations of fluorescence imaging.
Implementation Method 1
Bioluminescence is produced by an enzyme (e.g., luciferase) that catalyzes oxidation of its specific substrate (such as luciferin is for the luciferase enzyme), resulting in the emission of light.
Data Source
AI summary
Disclosed herein are bioluminescent indictors comprising a bioluminescent peptide split by a binding peptide capable of binding a ligand. The bioluminescent indicator bioluminesces upon binding of the binding peptide to its ligand to bring the regions of the bioluminescent peptide into such proximity that the indicator bioluminesces. The bioluminescent indicator may further comprise a leader domain and a transmembrane domain. The bioluminescent indicator acts as a biosensor that can detect and quantify a ligand without the need for an additional light source. Methods for imaging internal body structures are also presented.