Device and method for nanoparticle sizing based on time-resolved on-chip microscopy

Patent metadata

Field	Value
Publication number	US-2018052425-A1
Application number	US-201615542794-A
Country	US
Kind code	A1
Filing date	Jan 22, 2016
Priority date	Jan 22, 2015
Publication date	Feb 22, 2018
Grant date	—

Abstract

A method for the label-free sizing of small, nanometer-sized objects such as particles includes a hand-held, portable holographic microscope that incorporates vapor condensation of nanolenses and time-resolved lens-free imaging. The portable device is used to generate reconstructed, time-resolved, and automatically-focused phase images of the sample field-of-view. The peak phase value for each object a function of working distance (z 2 ) and condensation time (t) is used to measure object size. The sizing accuracy has been quantified in both monodisperse and heterogeneous particle solutions, achieving an accuracy of +/−11 nm for particles that range from 40 nm up to 500 nm. For larger particles, the technique still works while the accuracy roughly scales with particle size.

First claim

1 . A device for the imaging and sizing of objects within a sample comprising:
a housing having an interior volume therein; an image sensor disposed in an upper portion of the housing and having an active region facing towards the interior volume; a sample holder having a lower surface that contains the objects thereon, the sample holder insertable into the housing adjacent to the active region of the image sensor; a fluid chamber disposed in the housing and exposed to the interior volume and having a heating element therein, the fluid chamber configured to hold a liquid therein; and an array of spatially separated light sources disposed in the housing and defining an optical path between the array of spatially separated light sources and the active region of the image sensor, wherein the sample holder, when inserted, is positioned within the optical path.

2 . The device of claim 1 , further comprising a computing device having one or more processors configured to generate time-resolved, super-resolution holograms from a plurality of low-resolution image frames obtained of the objects by the image sensor when illuminated by the spatially separated light sources and extract peak phase values from phase image reconstructions obtained from the super-resolution holograms, wherein the one or more processors outputs a size of the objects based on the peak phase value values.

3 . The device of claim 1 , wherein the fluid chamber contains polyethylene glycol (PEG).

4 . The device of claim 1 , wherein the fluid chamber contains water.

5 . The device of claim 1 , further comprising a computing device having one or more processors configured to generate time-resolved, super-resolution holograms from a plurality of low-resolution image frames obtained of the objects by the image sensor when illuminated by the spatially separated light sources, wherein the image frames are obtained over a period of time t.

6 . The device of claim 5 , wherein the one or more processors are configured to back-propagate the super-resolved holograms obtained over the period of time t to multiple z 2 distances to generate phase image reconstructions of the objects.

7 . The device of claim 6 , wherein the one or more processors are configured to recover peak phase values of the objects as a function of distance z 2 and time t.

8 . The device of claim 7 , wherein the one or more processors are configured to count the objects and iteratively remove those objects from the phase image reconstructions having a peak phase value above a decreasing threshold value followed by recovering peak phase values for the remaining objects after the removal.

9 . The device of claim 8 , wherein the one or more processors are configured to merge peak phase values for all objects as function of distance z 2 and time t.

10 . The device of claim 9 , wherein the one or more processors applying a focusing criterion to remove spurious objects based on peak phase values as a function of z 2 values.

11 . The device of claim 10 , the one or more processors configured to identify the peak phase value for remaining non-spurious objects and outputting an object count and size of the counted objects based on the identified peak phase value.

12 . The device of claim 5 , the one or more processors are configured to track peak phase values for each object for all or some z 2 and t values.

13 . A method of imaging and sizing objects comprising:
loading the objects on a substrate; subjecting the substrate to evaporated liquid that forms nanolenses over the objects; obtaining a plurality of low-resolution image frames of the objects at multiple times t using an array of spatially separated light sources and an image sensor, wherein the objects of interest are located within an optical path between the spatially separated light sources and the image sensor; generating a super-resolved hologram from a plurality of low-resolution image frames obtained of the objects by the image sensor obtained at the multiple times t; back-propagating the super-resolved hologram to multiple z 2 distances; recovering phase images of the objects and counting objects having a phase value over a threshold value; masking the already counted objects and measuring the phase value of remaining objects and counting objects having a phase value over a reduced threshold, wherein this step is repeated a plurality of times; merging peak phase values for each object for all z 2 and t values; applying a focusing criterion to remove spurious objects based on z 2 values; and identifying the peak phase value for remaining non-spurious objects and outputting a size based on the identified peak phase value for the remaining non-spurious objects.

14 . The method of claim 13 , wherein the substrate, spatially separated light sources, image sensor, and the evaporated liquid are contained within a single portable, handheld device.

15 . The method of claim 13 , wherein the liquid comprises PEG or water.

16 . The method of claim 13 , wherein at least some of the objects comprise nanometer or micrometer sized particles.

17 . The method of claim 13 , wherein the objects range from about 40 nm to millimeter-sized objects.

18 . The method of claim 13 , wherein the substrate is continuously exposed evaporated liquid for several minutes.

19 . The method of claim 13 , wherein the masking operation is performed between 2 and 5 times.

20 . A device for the imaging and sizing of objects within a sample comprising:
a housing having an interior volume therein; an image sensor disposed in the housing and having an active region facing towards the interior volume; a sample holder having a surface that contains the objects thereon, the sample holder insertable into the housing adjacent to the active region of the image sensor; a fluid chamber disposed in the housing and exposed to the interior volume and having a heating element therein, the fluid chamber configured to hold a liquid therein; and one or more light sources disposed in the housing and defining an optical path between the one or more light sources and the active region of the image sensor, wherein the sample holder, when inserted, is positioned within the optical path.

21 . The device of claim 20 , wherein the one or more light sources comprises an array of spatially separated light sources.

Assignees

• Univ California

Inventors

• Ozcan Aydogan
• Mcleod Euan
• Dincer Tevfik Umut

Classifications

• G01B9/021

  using holographic techniques · CPC title

• G03H2001/261

  in optical contact · CPC title

• G03H1/26 Primary

  Processes or apparatus specially adapted to produce multiple {sub-} holograms or to obtain images from them, e.g. multicolour technique · CPC title

• G01N15/1429 Primary

  Signal processing · CPC title

• G03H2001/0447

  In-line recording arrangement · CPC title