Digital Holographic Microscope Flow Cytometer Throughput
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Solution Overview
Problem
Existing flow cytometers face limitations in object throughput rate, accuracy, and cost, with low throughput rates, complex operation requirements, high expenses, and the need for invasive fluorescent markers, which restrict their efficiency and usability in scientific research and clinical applications.
Innovation Solution
A flow cytometric system incorporating a digital holographic microscope (DHM) for observing, analyzing, and separating objects in a liquid sample, which uses interferometric and fluidic systems to guide objects through an illumination beam, enabling post-acquisition focusing and eliminating the need for optical focusing, and utilizing partially coherent light sources to reduce costs and enhance throughput.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional flow cytometry with optical focusing is used, then measurement precision is achieved, but object throughput rate is limited and device complexity increases
Solution Approach 1:
The patent removes the optical focusing mechanism from the flow cytometer system entirely. Instead of using traditional optical lenses and focusing mechanisms to achieve sharp images, the system captures holographic data from objects at various depths and uses digital processing to reconstruct focused images post-acquisition. This extraction of the optical focusing component simplifies the device structure while maintaining imaging capability.
Solution Approach 2:
The system performs preliminary capture of holographic data from all objects in the sample volume simultaneously, before any focusing or selection is performed. The digital holographic microscope records interference patterns that contain information about objects at different depths and positions. Subsequent digital processing then applies focusing operations to reconstruct sharp images of selected objects, enabling post-acquisition focusing that eliminates the need for mechanical focusing mechanisms during data capture.
2Measurement precision
If fluorescent markers are used for object identification, then measurement precision improves, but operational complexity and cost increase
Solution Approach 1:
The patent extracts and eliminates the requirement for fluorescent markers and related application systems. Instead of relying on fluorescent labeling to identify and differentiate objects, the digital holographic microscope captures the natural optical properties of objects including phase, amplitude, and scattering characteristics. These intrinsic properties provide sufficient contrast and identification capability without requiring external fluorescent tags, thereby removing the complexity of marker application, storage, and handling systems.
Solution Approach 2:
The system utilizes the objects' own optical properties for identification and characterization. Digital holographic microscopy naturally captures phase information, amplitude variations, and scattering patterns that are inherent to each object's physical structure, composition, and state. This self-characterization approach eliminates the need for external fluorescent markers, allowing objects to serve themselves for identification purposes through their intrinsic optical signatures.
3Measurement precision
If traditional optical microscopy is used for object observation, then imaging quality is achieved, but object throughput rate decreases
Solution Approach 1:
The patent transitions from traditional 2D optical microscopy to 3D digital holographic microscopy. By capturing the full complex wavefront (amplitude and phase) of light scattered by objects, the system obtains three-dimensional information about object position, shape, and internal structure in a single capture. This dimensional enhancement allows simultaneous observation of multiple objects at different depths within the sample volume, increasing throughput while maintaining or improving imaging quality through digital refocusing capabilities.
Solution Approach 2:
The system creates digital copies of objects through holographic reconstruction rather than requiring direct optical focusing for each object. The captured holographic data serves as a digital replica containing complete optical information about objects. This digital copying approach allows rapid processing and reconstruction of multiple objects without the time-consuming mechanical focusing operations required by traditional optical microscopy, thereby increasing throughput rate while preserving imaging quality.
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 system achieves higher throughput rates, provides accurate 3D imaging, reduces operational complexity and costs, and eliminates the need for invasive markers, enabling efficient analysis and separation of objects with improved quality and reduced expenses.
Implementation Method 1
U.S. Pat. No. 7,463,366 discloses a method and device for obtaining a sample with three-dimensional microscopy, in particular a thick biological sample and the fluorescence field emitted by the sample. One embodiment includes obtaining interferometric signals of a specimen
Implementation Method 2
The laser beam can scatter from the objects, or the illumination means can induce fluorescence in the objects if these have been marked with fluorescent markers
Implementation Method 3
the illumination means can induce fluorescence in the objects if these have been marked with fluorescent markers
Data Source
AI summary
The current invention concerns a flow cytometric system and method for observing, analyzing and/or separating objects in a liquid sample, comprising a digital holographic microscope (DHM) and at least one fluidic system, whereby the DHM comprises illumination means, an interferometric system and digital recording means, whereby the fluidic system is capable of guiding said objects through an illumination beam of the illumination means of said DHM, whereby the fluidic system comprises a mechanism for inducing a liquid sample stream through the fluidic system, whereby preferably the fluidic system comprises a stream size controlling device for controlling the transverse dimensions of a liquid sample stream inside said fluidic system, preferably said stream size controlling device is capable of lining up the objects one-by-one or multiple objects at a time in said liquid sample stream.