Detection of agglutination by optical density measurement
Inventors
Rowlen, Kathy Lou • Fraikin, Jean-Luc • Birks, John William • Williford, Craig J.
Assignees
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Publication Number
US-9360433-B1
Publication Date
2016-06-07
Expiration Date
Abstract
A system for the indirect detection of agglutination in an agglutination assay using optical density measurement and a reaction vessel. Light emitted by light source is transmitted through reaction vessel containing components of an agglutination reaction that is detected by light detector. As particles in the reaction vessel settle in the absence of agglutination they are concentrated in a reaction vessel lower volume and increase the optical density of the light path through the reaction vessel. Light detector generates an output signal related to said optical density. Said output signal is read and interpreted by an instrument to detect a presence or absence of agglutination. Other embodiments are described and shown.
Core Innovation
The invention provides an automated agglutination detection approach in which particles in one or more reaction vessels are arranged with a predetermined shape so that a force causes particles to concentrate about a light path, increasing an optical density of the light path. Light is passed along the light path through the reaction vessels to one or more light detectors that generate an electrical signal varying with the intensity of the detected light. The processor analyzes the electrical signal and compares an output signal to a threshold to output an indication of agglutination when the output signal is compared to a threshold.
A key aspect is the geometry of at least one reaction vessel, which comprises an upper volume, a lower volume, and a transition region positioned between the upper volume and the lower volume. The upper volume has a cross-sectional area greater than a cross-sectional area of the lower volume, and the transition region profile causes particles to move from the upper volume into the lower volume to be concentrated about the light path. The transition region profile comprises two curved sections.
The disclosed system further includes features that support optical detection, including a reaction vessel arrangement with light travelling on the light path to the light detectors and optional components for analyzing and outputting results based on threshold comparison. The document describes scaling and arrangement of multiple vessels and detection components, including multiwell array context and arrayed or distributed light sources and detectors, with interpretation based on the electrical signal and threshold.
Claims Coverage
The document provides two independent claims, a method and a device, that share the same core inventive concept: using a predetermined reaction-vessel geometry to concentrate particles about a light path to increase optical density, and determining agglutination by analyzing detector-generated electrical signals against a threshold. Across the dependent claims, the coverage refines optical/material properties of vessel surfaces, optional system components for illumination and output, and multi-vessel shape variation.
Particle concentration about a light path using predetermined reaction vessel shape
The reaction vessel has a predetermined shape such that a force causes particles to concentrate about the light path, increasing optical density of the light path.
Threshold-based agglutination indication from detector electrical signal
A processor analyzes an electrical signal generated by one or more light detectors that varies with intensity of detected light, and outputs a signal or indication of agglutination in at least one reaction vessel when the output signal is compared to a threshold.
Upper volume, lower volume, and transition region with two curved sections
At least one reaction vessel comprises an upper volume, a lower volume, and a transition region positioned between the upper volume and the lower volume, where the upper volume has a cross-sectional area greater than the cross-sectional area of the lower volume, and the transition region profile causes particles to move from the upper volume into the lower volume to be concentrated about the light path, with the profile comprising two curved sections.
Passing light along the light path through reaction vessels to light detectors
Light is passed along the light path through the reaction vessels to one or more light detectors positioned to detect light travelling on the light path and to generate the electrical signal that varies with the intensity of the detected light.
Across the independent method and device, the central inventive features are the predetermined reaction-vessel geometry that concentrates particles about a light path to increase optical density, and a processor that compares detector electrical signals to a threshold to indicate agglutination. The vessel geometry is specifically defined with an upper volume, lower volume, and transition region having a profile with two curved sections.
Stated Advantages
Enables automatic detection of agglutination by detecting changes in optical density via a detector-generated electrical signal compared to a threshold.
Documented Applications
Agglutination detection demonstrated for influenza B with detector output described as an output voltage versus time and comparison to negative controls.
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