Compact optical system for substanially simultaneous monitoring of samples in a sample array

Inventors

Abbott, Richard DavidRiley, Patrick L.Evans, Zackery KentNay, Lyle M.

Assignees

Biofire Defense LLC

Publication Number

US-10698190-B2

Publication Date

2020-06-30

Expiration Date

2033-03-15

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Abstract

Optical systems and apparatuses configured for enabling substantially simultaneous observation of a plurality of points in an array from a common reference point. Without the optical systems and apparatuses disclosed herein, less than all of the plurality of points can be observed substantially simultaneously from the common reference point.

Core Innovation

The invention relates to optical systems and apparatuses configured for enabling substantially simultaneous observation and monitoring of a plurality of points of interest in an array from a common reference point. For example, the system enables the simultaneous observation of all sample wells in a microplate, such as a 96-well plate, from a common location. Without the disclosed optical systems and apparatuses, less than all of the points can be observed substantially simultaneously.

The problem addressed is that in high-throughput biological assays using multi-well sample plates, standard optical devices (such as cameras or detectors) placed at a typical, close distance cannot see the bottoms of all wells at once due to physical obstructions from the well walls and plate geometry. Traditional solutions, such as placing the detector far above the plate or using complex lensing systems, result in large, cumbersome, or expensive equipment and can lead to issues such as light diffusion, loss of signal strength, cross-talk, and alignment problems.

The core innovation is an optical system that includes non-focusing optical means—such as a mirror having a compound curvature (e.g., a dual-curved bi-conic or paraboloid mirror), a curved sample block, or a complementary arrangement of single-curved elements—in the optical path. These elements enable a substantially unimpeded and equal-length optical path for each point of interest to the observation point, allowing an observation apparatus (such as a camera) to acquire images or monitor signals (e.g., fluorescence, luminescence) from all wells in an array simultaneously and at a reduced form factor without the use of traditional focusing lenses.

Claims Coverage

The patent contains two independent claims that define the key inventive features of the disclosed optical observation apparatus and system for simultaneous monitoring of samples in an array.

Simultaneous observation of multiple samples using a non-apex paraboloid reflective element

An apparatus including: - A sample block with a plurality of recessed receptacles for sample containers positioned at one end of a body. - An observation element at the other end of the body, containing a light source and camera, where the light source transmits light toward the sample block. - A reflective element (mirror) positioned above the sample block with a single reflective surface formed as a non-apex portion of a paraboloid, directing light simultaneously from the light source to each sample container and reflecting their images simultaneously to the observation element. - The reflected images are distorted into a fan shape and a computer processes and corrects the distortion to yield an undistorted image.

System for real-time monitoring of biological samples using a paraboloid mirror for simultaneous imaging

A system comprising: - A thermocycler with a sample block including multiple recessed receptacles for sample containers. - An observation element with a light source and camera positioned opposite the sample block, with the light source transmitting light toward the sample block. - A reflective element above the sample block featuring a single reflective surface as a non-apex portion of a paraboloid, directing light to all sample containers simultaneously and reflecting images simultaneously back to the observation element. - Images are distorted to a fan shape and a computer corrects the distortion to produce an undistorted image.

The independent claims protect an apparatus and system that enable simultaneous optical monitoring of multiple samples using a specifically shaped paraboloid mirror to direct and reflect light, with a computer correcting image distortion for accurate observation.

Stated Advantages

Enables substantially simultaneous observation of all points of interest in an array from a common reference point, which is not possible with conventional systems without moving the detector far from the sample plate.

Reduces the form factor and complexity of the instrument by eliminating the need for focusing lenses or placing observation devices at large distances from the sample array.

Provides a substantially unimpeded optical path and equalizes ray lengths from all sample points to the observation device, minimizing issues such as signal loss, cross-talk, and sample obscuration.

Allows optical systems to collect data from or monitor any optically detected assay in a multi-well or planar array format in a compact and efficient manner.

Facilitates correction of consistent image distortion, allowing for reliable data processing across measurements.

Documented Applications

Real-time fluorescent monitoring of biological samples undergoing polymerase chain reaction (PCR) or nucleic acid amplification.

High-throughput screening of assays performed in multi-well plate formats, including but not limited to reporter gene assays, protein melting assays, nucleic acid melting assays, direct fluorescent antibody assays, and turbidimetric assays.

Use in thermocycling systems for simultaneous optical monitoring of fluorescence in biological samples within sample containers or multi-well plates.

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