Dynamic Nano-DIHM for real-time and in-situ measurement of particles such as viruses

Patent metadata

Field	Value
Publication number	US-12584846-B2
Application number	US-202218076503-A
Country	US
Kind code	B2
Filing date	Dec 7, 2022
Priority date	Dec 7, 2022
Publication date	Mar 24, 2026
Grant date	Mar 24, 2026

Abstract

A real-time, in situ and automated technology and method for dynamic observation of airborne viruses has been developed, and its application for airborne viruses, using a model virus, MS2 bacteriophage, and SARS-COV-1 RNA, has been demonstrated. There is described a method of performing measurements using a digital in-line holographic microscope (DIHM). The method generally has: propagating a light beam through a pinhole, across a medium including particles, and to a sensor; acquiring, with the sensor, a plurality of holograms, the holograms including scattering information of the particles; and determining, from a reconstruction of the holograms, at least one of shape, size, intensity and phase of the particles from the scattering information of said particles.

First claim

What is claimed is:

1 . A method of performing measurements comprising:
propagating a light beam through a pinhole, and propagating a diverging beam exiting the pinhole first across a medium including particles and then to a sensor; acquiring, with the sensor, a hologram constructed from the interaction between the diverging beam and particles, the hologram including scattering information of the particles; performing a numerical reconstruction of the hologram; changing the distance between the pinhole and the medium including the particles and repeating the steps of propagating, acquiring, and preforming a numerical reconstruction for a plurality of different planes extending between the pinhole and the medium including the particles the planes being perpendicular to an orientation defined between the pinhole and the sensor; and determining, from the numerical reconstructions of the holograms, at least one of shape, size, intensity and phase of the particles from the scattering information of said particles.

2 . The method of claim 1 wherein the medium is a fluid, the method further comprising circulating the fluid including the particles across the light beam, between the pinhole and the sensor.

3 . The method of claim 2 wherein said circulating includes circulating the fluid within a flow tube.

4 . The method of claim 3 wherein the flow tube includes an inlet and an outlet, said circulating including circulating the medium from the inlet to the outlet forming a directional moving flow.

5 . The method of claim 3 further comprising the flow tube partially reflecting the diverging light beam backward multiple times, superposing diverging light coming directly from the pinhole with reflected light which appears to come from multiple virtual pinholes, wherein the particles are ≤200 nm.

6 . The method of claim 2 wherein the fluid includes water, and the light beam has a wavelength within the visible range of the electromagnetic spectrum.

7 . The method of claim 6 wherein the wavelength of the light beam is about 405 nm.

8 . The method of claim 1 wherein, for particles having a dimension below one micrometer, a distance between the pinhole and the medium is within 5 micrometers, preferably with 4 micrometers, and most preferably within 3 micrometers.

9 . The method of claim 1 wherein the sensor has a field of view of at least 25 mm 2 , preferably at least 30 mm 2 and most preferably at least 40 mm 2 .

10 . The method of claim 1 wherein said determining including identifying which of the reconstructions corresponding to a given one of the different planes has a sharpness above a given sharpness threshold.

11 . The method of claim 1 wherein said planes are spaced apart by 0.01 micrometers or less from each other.

12 . The method of claim 1 wherein said performing a numerical reconstruction includes performing at least three deconvolution steps.

13 . The method of claim 1 wherein the step of determining at least one of shape, size, intensity and phase of the particles further includes determining dynamic information of the particles over a period of time.

14 . The method of claim 1 wherein the particles have a particle size of less than 100 microns, preferably less than 100 nm.

15 . The method of claim 1 wherein the medium including the particles is an aerosol.

16 . The method of claim 15 wherein the aerosol is a bioaerosol, the bioaerosol being a virus aerosol of airborne viruses, the bioaerosol being a virus nanoparticle or microparticle aerosol, comprising airborne particles or droplets with a virus.

17 . The method of claim 15 wherein the aerosol includes microplastic particles.

18 . The method of claim 1 wherein the particles are biological particles containing biological material, the step of acquiring being preceded by irradiating the medium with a secondary light source, the secondary light source emitting light in the ultraviolet range of the electromagnetic spectrum, the biological particles being photolyzed when irradiated by the secondary light source.

19 . The method of claim 1 wherein the step of acquiring the plurality of holograms is followed by reconstructing the holograms in an automated manner by a computer.

20 . The method of claim 1 wherein the step determining at least one of shape, size, intensity and phase of the particles is followed by identifying a type for each particle in an automated manner with a computer having been trained using machine learning.

21 . The method of claim 1 wherein the performing a numerical reconstruction includes processing the hologram according to a Kirchhoff-Hemlholtz transform followed by performing a fast-Fourier transform (FFT).

22 . The method of claim 21 further comprising performing real-time volumetric reconstruction and 4D particle tracking.

23 . The method of claim 1 further comprising measuring phase shift from the numerical reconstruction of the holograms, and determining refractive index of said particles based on a known size of the particles and on the phase shift.

Assignees

• The Royal Institution For The Advancement Of Learning/Mcgill Univ

Inventors

• Ariya Parisa A
• Pal Devendra

Classifications

• G01N15/01 Primary

  specially adapted for biological cells, e.g. blood cells (investigating sedimentation of particle suspensions in blood G01N15/05) · CPC title

• G01N2015/1493

  Particle size · CPC title

• G03H2001/005

  in microscopy, e.g. digital holographic microscope [DHM] · CPC title

• G01N2015/1497

  Particle shape · CPC title

• G03H2001/2244

  Means for detecting or recording the holobject · CPC title