Rotating Sample Holder for High-Throughput Parallel Imaging
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Solution Overview
Problem
Current imaging techniques, such as confocal microscopy, face limitations in achieving high frame rates, high spatial resolution in three dimensions, and low cost, making them unsuitable for widespread applications beyond well-funded research labs, particularly in studying micro-biologically relevant matter.
Innovation Solution
The apparatus employs a rotating cylindrical sample holder to move the sample through an array of sub-observation volumes defined by overlapping illumination and detection foci, using an array of pinholes and avalanche photo diodes in Geiger mode for high-speed, time-resolved detection, allowing for diffraction-limited resolution and increased throughput.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a pinhole is used to filter out light from outside the focal plane in conventional confocal microscopy, then contrast is enhanced, but the observation volume is severely restricted requiring point-by-point scanning which limits throughput
Solution Approach 1:
The patent divides the detection system into multiple independent detection channels, each with its own pinhole and detector. This segmentation allows simultaneous detection at multiple positions, replacing the sequential point-by-point scanning with parallel detection, thus resolving the contradiction between maintaining contrast through pinhole filtering and achieving high throughput
Solution Approach 2:
The patent transitions from one-dimensional scanning (moving a single observation volume through the sample) to multi-dimensional parallel detection (having multiple observation volumes detected simultaneously). By adding the dimension of multiple detection channels operating in parallel, the system achieves both high contrast and high throughput
2Device complexity
If the same optics are used for both illuminating and viewing in conventional confocal microscopy, then device complexity is reduced, but the observation volume is limited and scanning is required
Solution Approach 1:
The patent segments the optical path into separate illumination and detection channels, with each channel having dedicated optics. This allows independent optimization of illumination and detection, enabling simultaneous multi-point observation without requiring complex scanning mechanisms, thus resolving the contradiction between simple optical configuration and high imaging speed
3Measurement precision
If a small focal width objective lens is used to achieve high resolution, then spatial resolution is improved, but the observation volume is restricted requiring scanning to image multiple points
Solution Approach 1:
The patent uses multiple objective lenses with small focal widths, each optimized for high spatial resolution, arranged in parallel detection channels. This segmentation allows each lens to maintain high resolution while the system as a whole achieves high throughput through parallel processing of multiple points simultaneously
Solution Approach 2:
The patent adds the dimension of multiple observation volumes operating in parallel. Instead of scanning a single high-resolution observation volume through the sample, the system creates multiple high-resolution observation volumes that detect simultaneously, resolving the contradiction between spatial resolution and imaging throughput
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 high-frame-rate, high-spatial-resolution imaging of large sample areas with improved signal-to-noise ratio and reduced photobleaching, facilitating applications like live cell imaging and pathology analysis at a lower cost, thereby making it suitable for point-of-care and general usage.
Implementation Method 1
detection means comprising one or more pinholes and avalanche photo diodes in Geiger mode
Implementation Method 2
Very often confocal microscopy is combined with fluorescence spectroscopy, where specific particles, e.g. proteins, are marked with fluorophores
Data Source
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AI summary
Apparatus for imaging a sample (109), said apparatus comprising: illumination means (101, 102, 103, 104, 105, 106, 107, 108) for illuminating said sample (109) simultaneously in a line focus or an array of foci; and detection means (108, 107, 106b, 111, 112, 113) for detecting photons emitted or scattered from a sample (109) simultaneously in an array of fields of view; wherein an array of sub-observation volumes in a sample (109), from which photons are emitted or scattered during imaging, is defined by the volumes in space where the line focus or array of foci from the illumination means (101, 102, 103, 104, 105, 106, 107, 108) overlap with the corresponding array of field of views of the detection means (108, 107, 106b, 111, 112, 113); a sample holder (110, 110a), preferably a cylindrical sample holder (110, 110a), configured to hold the sample (109) at a surface thereof, said sample holder (110, 110a) being rotatably arranged such that at least a portion of said sample (109) can be transported through at least one of said sub-observation volumes by rotating the sample holder (110, 110a).