Portable TIRF Microscope With Prism-Based Single-Molecule Detection
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Solution Overview
Problem
Current point-of-care devices compromise sensitivity to achieve portability and affordability, failing to detect single fluorescent molecules due to their design and operational complexity, which is typically found in benchtop fluorescence microscopes.
Innovation Solution
A portable total internal reflection fluorescence microscope with a modular design comprising a laser stage, objective stage, and sample stage, utilizing a prism for total internal reflection with an incidence angle of 75° to 90°, compatible with smartphones and other portable devices, allowing detection of single fluorescent molecules without additional optics or skilled personnel.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If benchtop fluorescence microscopes are used to detect single molecules, then detection sensitivity is improved, but device size and weight increase making it non-portable
Solution Approach 1:
The microscope system is divided into separate functional modules: a portable box containing the laser and control electronics, a prism module for total internal reflection, and a smartphone camera module. This segmentation allows each component to be optimized independently and enables portability while maintaining single-molecule detection capability.
Solution Approach 2:
A prism is introduced as an intermediary component to achieve total internal reflection of the laser beam. This prism acts as the key element that enables TIRF microscopy in a portable format, creating the evanescent wave necessary for single-molecule detection without requiring the complex optical bench of traditional microscopes.
2Measurement precision
If benchtop fluorescence microscopes are used to detect single molecules, then detection sensitivity is improved, but device complexity increases requiring skilled personnel
Solution Approach 1:
The portable microscope is designed to work with standard smartphone cameras, which are ubiquitous and user-friendly. The system uses a standard laser diode and a simple prism geometry that can be aligned using everyday objects. This universality allows anyone with a smartphone to operate the device without specialized training in microscopy.
Solution Approach 2:
The prism geometry is designed to be self-aligning within a tolerance range, reducing the need for precision alignment procedures. The system automatically maintains the total internal reflection condition as long as the prism is positioned within the specified angular range, eliminating the need for skilled operators to perform complex alignment procedures.
3Ease of operation
If point-of-care devices are made portable and affordable, then ease of use is improved, but detection sensitivity decreases preventing single molecule detection
Solution Approach 1:
The system changes the illumination mode from conventional wide-field or confocal fluorescence to total internal reflection fluorescence. This parameter change in the excitation geometry creates an evanescent wave that exponentially decays from the coverslip surface, providing inherent optical sectioning and background rejection that enables single-molecule detection with simple, portable optics.
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
The microscope achieves single molecule detection with high sensitivity, portability, affordability, and ease of use, enabling super-resolution imaging and compatibility with various glass samples without realignment, suitable for diverse applications including early disease diagnosis and agricultural uses.
Implementation Method 1
the laser stage is arranged such that the laser beam has an incidence angle at the prism comprised in the range of 75° to 90°, the incidence angle being the angle formed by the laser beam at the prism with respect to a normal of a main plane of the sample stage, so as to have a total internal reflection of the laser beam
Implementation Method 2
a portable total internal reflection fluorescence microscope
Implementation Method 3
an objective stage, comprising an objective
Data Source
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AI summary
The present invention concerns a portable total internal reflection fluorescence microscope (1) comprising: - a portable box (40) comprising: - a laser stage (10), comprising a laser (100), - an objective stage (30), comprising an objective (300), - a sample stage (20), comprising a sample (200) to be observed, wherein the sample stage (20) is disposed between the laser stage (10) and the objective stage (30), - a support (50) on the portable box (40), arranged for receiving a camera (21,22), wherein the sample stage (20) comprises a prism (210), wherein the laser stage (10) is arranged such that the laser beam (110) has an incidence angle (θ) at the prism (210) comprised in the range of 75° to 90°, the incidence angle (θ) being the angle formed by the laser beam (110) at the prism (210) with respect to a normal (N) of a main plane of the sample stage (20), so as to have a total internal reflection of the laser beam (110) and thus detect a single fluorescent molecule in the sample (200).