Lensless Digital Inline Microscope for Biochip Target Counting
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Solution Overview
Problem
Existing optical magnification-based quantitative analysis devices face challenges with narrow viewing fields, long analysis times, and high costs, limiting their ability to accurately detect and count target substances on biochips without fluorescence-labeled materials.
Innovation Solution
A method and device using a lensless digital inline microscope with a CMOS image sensor that acquires low-resolution images from multiple angles, reconstructs high-resolution images, and counts target substances, including those bound to magnetic particles, without the need for fluorescence-labeled materials, by applying electromagnetic forces and using a pinhole aperture for improved resolution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If optical magnification adjustment system (microscope-like manner) is used to improve detection resolution, then single target substance detection accuracy is improved, but analysis time increases and observation area is reduced
Solution Approach 1:
The patent transitions from 2D optical magnification to 3D depth information by measuring shadow intensity variations at different focal planes. The depth-resolved shadow imaging captures target substances at multiple depth levels simultaneously, enabling high-resolution detection across the entire observation area without sequential scanning, thus resolving the contradiction between detection resolution and analysis speed.
Solution Approach 2:
The patent segments the imaging process into multiple focal plane measurements, capturing shadow images at different depths. By processing these segmented depth layers independently and combining them, the system achieves high-resolution detection of individual target substances throughout the observation volume without sacrificing analysis speed.
2Measurement precision
If mechanical detection method with high-sensitivity sensor is used to detect target substances, then detection sensitivity is improved, but noise from sample and detection environment increases and device complexity increases
Solution Approach 1:
The patent replaces complex mechanical detection systems with optical shadow imaging. By using light transmission and shadow formation principles, the system achieves high detection sensitivity without requiring complex electronic circuits or sensitive mechanical sensors, thereby reducing device complexity while maintaining detection capability.
Solution Approach 2:
The patent introduces shadow imaging as an intermediary measurement method. Instead of directly detecting target substances with sensitive sensors, the system uses shadow intensity variations as an intermediary signal that is less susceptible to environmental noise and requires simpler detection electronics.
3Measurement precision
If fluorescence-labeled material is used to detect target substances, then detection accuracy is improved, but cost increases and analysis time increases
Solution Approach 1:
The patent extracts the detection function from fluorescence labeling and implements it through optical shadow imaging of magnetic particles. By removing the fluorescence labeling step entirely and using the inherent optical properties of magnetic particles, the system achieves detection accuracy without the time-consuming labeling process.
Solution Approach 2:
The patent enables magnetic particles to serve their dual function of target binding and optical detection without requiring additional fluorescence labels. The magnetic particles themselves provide the detection signal through their optical shadow properties, eliminating the need for separate labeling reagents and procedures.
4Device complexity
If conventional optical detection is used to observe target substances, then device simplicity is maintained, but detection resolution is insufficient for single target substance identification
Solution Approach 1:
The patent enhances conventional optical detection by adding the depth dimension through focal plane variation. By measuring shadow images at multiple focal distances and processing the depth information, the system achieves high detection resolution for single target substances while maintaining the simplicity of optical imaging without requiring complex magnification systems.
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 enables rapid and accurate quantitative analysis of target substances across a wide analysis region, increasing detection efficiency and reducing costs by providing high-resolution images for precise counting of magnetic particle-target substance complexes on biochips.
Implementation Method 1
a light irradiator which emits light at a plurality of angles
Implementation Method 2
a lensless digital inline microscope based on a CMOS image sensor to acquire shadow images
Implementation Method 3
acquire a high-resolution image including images of the plurality of target substances based on the plurality of low-resolution shadow images
Implementation Method 4
applying electromagnetic forces and using a pinhole aperture for improved resolution
Data Source
AI summary
A method of quantitatively analyzing a target substance includes a step of irradiating a biochip, which includes a plurality of target substances excluding a fluorescence-labeled material, with light; a step of acquiring a plurality of low-resolution images for a region including the plurality of target substances using an image sensor, a step of acquiring a high-resolution image based on the plurality of low-resolution images; and a step of counting the plurality of target substances in the high-resolution image; and a device for quantitatively analyzing a target substance using the method.