Apparatuses, systems and methods for imaging micro-objects

Inventors

Lundquist, Paul M. • Lebel, Paul M. • Jess, Phillip Ronald Thomas

Assignees

Bruker Spatial Biology Inc

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Publication Number

US-11731129-B2

Patent

Publication Date

2023-08-22

Expiration Date


Abstract

The present disclosure relates to an optical apparatus for imaging and/or manipulating micro-objects in a microfluidic device, such as a light-actuated microfluidic (LAMF) device, and related systems and methods. The optical apparatus can comprise a structured light modulator, a first and a second tube lens, an objective lens, a dichroic beam splitter, and an image sensor. The structured light modulator can be configured to receive unstructured light beams and transmit structured light beams for illuminating micro-objects located within an enclosure of the microfluidic device and/or selectively activating one or more of a plurality of dielectrophoresis (DEP) electrodes of the microfluidic device. The image light beams received by the image sensor can be used to form an image of at least a portion of the microfluidic device.

Core Innovation

The invention provides an optical apparatus for imaging micro-objects located in an enclosure of a microfluidic device using structured light illumination. A structured light modulator receives unstructured light beams from a first light source and reflects or transmits structured light beams suitable for illuminating micro-objects in the enclosure. The structured light beams are captured and transmitted by a first tube lens, and imaging light beams from an objective lens are relayed by a first dichroic beam splitter and a second tube lens to an image sensor that forms an image of a field of view comprising at least a portion of the enclosure.

The optical imaging train captures and transmits structured light beams and image light beams through a first tube lens, an objective lens, and a dichroic beam splitter, and then images a field of view onto an image sensor. The system defines an optical path from the structured light modulator to the enclosure and from the objective lens back through relay optics toward the image sensor to form an image of the field of view.

A key optical design element is the use of tube-lens optical configurations characterized by lens surface shapes and radius-of-curvature sign relationships. In at least one tube lens, the lens includes convex and concave surfaces with first, third, and fourth radii of curvature having specified signs, together with a condition in which a front focal point and a back focal point are not equally spaced from a midpoint of the tube lens. The apparatus is characterized by an aperture stop at the back of the objective lens with at least 25 mm.

Claims Coverage

The provided independent claims are clm-00001 and clm-00028. Across these independent claims, the main inventive features include structured-light modulation for illuminating micro-objects in a microfluidic enclosure and a specific imaging relay using tube lenses, a dichroic beam splitter, and an image sensor, together with defined tube-lens geometry constraints and an objective back aperture stop minimum size.

Structured light modulator for microfluidic enclosure illumination

A structured light modulator configured to receive unstructured light beams from a first light source and reflect or transmit structured light beams suitable for illuminating micro-objects located in the enclosure of the microfluidic device.

First tube lens with specified lens geometry and focal-point asymmetry

A first tube lens configured to capture and transmit the structured light beams from the structured light modulator, comprising a first surface having a convex shape and a first radius of curvature; a second surface having a second radius of curvature; a third surface having a concave shape and a third radius of curvature; and a fourth surface having a concave shape and a fourth radius of curvature; wherein the first radius of curvature is positive, the third radius of curvature is negative, and the fourth radius of curvature is negative; and wherein a front focal point and a back focal point of the first tube lens are not equally spaced from a midpoint of the first tube lens.

Objective lens imaging with a back aperture stop

An objective lens configured to capture and transmit image light beams from a field of view comprising at least a portion of the enclosure of the microfluidic device, wherein the apparatus is characterized by an aperture stop at the back of the objective lens, wherein the aperture stop is at least 25 mm.

Dichroic beam splitter combining structured and image light beams

A first dichroic beam splitter configured to receive and reflect or transmit the structured light beams from the first tube lens, and further configured to receive and transmit or reflect the image light beams from the objective lens.

Second tube lens imaging relay to the image sensor

A second tube lens configured to receive and transmit the image light beams from the first dichroic beam splitter, and an image sensor configured to receive the image light beams from the second tube lens, wherein the image sensor forms an image of the field of view based upon the image light beams received from the second tube lens.

Second tube lens with specified lens geometry and focal-point asymmetry

In clm-00028, the second tube lens comprises a first surface having a convex shape and a first radius of curvature; a second surface having a second radius of curvature; a third surface having a concave shape and a third radius of curvature; and a fourth surface having a concave shape and a fourth radius of curvature; wherein the first radius of curvature is positive, the third radius of curvature is negative, and the fourth radius of curvature is negative; and wherein a front focal point and a back focal point of the second tube lens are not equally spaced from a midpoint of the second tube lens.

Across clm-00001 and clm-00028, the optical apparatus centers on structured light illumination of micro-objects within a microfluidic device enclosure, followed by an imaging relay that uses tube lenses and a first dichroic beam splitter to route both structured light and image light to an image sensor. The claims also require a back aperture stop at the objective lens with at least 25 mm and impose tube-lens geometry constraints including sign-defined radii of curvature and focal-point spacing asymmetry relative to the lens midpoint.

Stated Advantages

Higher resolution by combining multiple low-resolution images based on angular illumination.

Iterative Fourier-domain image reconstruction for angular imaging/FOURIER ptychographic microscopy (FPM).

Documented Applications

Imaging micro-objects in an enclosure of a microfluidic device.

Angular imaging and Fourier ptychographic microscopy (FPM) using structured-light modulation.

Illumination and imaging of a microfluidic sample within a microfluidic device enclosure, including embodiments with additional illumination for heating or excitation.

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