# US 12,007,315 B2 · Sample collection and handling for delayed analysis

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- Number: US 12,007,315 B2
- Document ID: US12007315B2
- Status: Granted
- Kind: B2
- Application number: 17/060,020
- Filed: 2020-09-30
- Published: 2021-01-21
- Granted: 2024-06-11
- Earliest claimed: 2017-02-08
- Assignees: Essenlix Corporation
- Applicants: Essenlix Corporation
- Inventors: Stephen Y. Chou; Wei Ding; Yufan Zhang; Ji Qi
- Web page: https://patentgrep.com/patent/US12007315B2

## CPC

- G01N 1/2813: {Producing thin layers of samples on a substrate, e.g. smearing, spinning-on (G01N1/30 takes precedence)}
- G01N 1/286: {involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising (microtomes G01N1/06; pulverising in general B02C; mixing in general B01F)}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention provides, among other things, devices, methods and applications of collecting, preserving, transporting, and analyzing tiny body fluids which have targeted biomarkers.

## Claims

### Claim 1

A method for sample collection and remote analysis, comprising:
(a) providing a sample holder comprising a first plate, a second plate, and spacers, wherein:
(i) the first and second plates are movable relative to each other into different configurations, including an open configuration and a closed configuration;
(ii) each of the plates comprises a surface that includes a sample contact area for contacting a sample that contains or is suspected of containing an analyte;
(iii) the spacers are fixed to one of the sample contact areas, wherein the spacers have a predetermined inter-spacer distance and a predetermined height, wherein at least one of the spacers are inside the sample contact area;
(iv) at least one of the two plates is transparent; and
(v) one or both of the two plates comprise a reagent on a surface thereof,
(b) collecting the sample to the sample contact area of one or both of the two plates at the open configuration;
(c) compressing the two plates into the closed configuration;
(d) imaging, after step (c), at least one image of the sample in the sample holder, wherein the imaging is through the transparent plate;
(e) sending the sample holder and the at least one image to a remote location; and
(f) analyzing, at the remote location, the sample and the at least one image to measure the analyte, wherein the analyzing uses the predetermined inter-spacer distance and the predetermined height to quantify the volume of the sample at the closed configuration, and uses the at least one image;
wherein the open configuration is a configuration in which the two plates are partially or entirely separated apart and a spacing between the two plates is not regulated by the spacers,
wherein in the closed configuration, which is formed after the sample is deposited when the two plates are in the open configuration, at least part of the sample is compressed by the two plates into a layer of highly uniform thickness of 200 μm or less, the layer is confined by the plates, and the thickness of the layer is regulated by the plates and the spacers.

### Claim 2 (depends on 1)

The method of claim 1, wherein one or both of the two plates comprise a visual mark for cutting the sample.

### Claim 3 (depends on 1)

The method of claim 1, wherein the imaging is performed with a camera on a smartphone with or without using an adaptor, wherein the adaptor comprises optical elements and/or lighting to facilitate the imaging, and the optical element comprises a lens or filter.

### Claim 4 (depends on 1)

The method of claim 1 further comprising a step of cutting out a part of the sample holder, wherein the cut-out part of the sample is analyzed.

### Claim 5 (depends on 1)

The method of claim 1 further comprising a step of measuring a lateral area of the sample holder and cutting out the lateral area from the sample holder, wherein the cut-out part of the sample is analyzed.

### Claim 6 (depends on 1)

The method of claim 1, wherein one or both of the plates further comprise a binding site, or a storage site, or both.

### Claim 7 (depends on 1)

The method of claim 1, further comprising a step of calculating a volume of a portion of the sample from a thickness of the portion of the sample regulated by the spacers and a lateral area of the portion of the sample.

### Claim 8 (depends on 1)

The method of claim 1, further comprising:
calculating the volume of a portion of the sample from a thickness of the portion of the sample regulated by the spacers and a lateral area of the portion of the sample, and
correcting an effect of a non-sample material, wherein the non-sample material is a material that is inside the sample but not from the sample.

### Claim 9 (depends on 1)

The method of claim 1, wherein the reagent comprises a preservative that preserves the sample on the sample holder.

### Claim 10 (depends on 1)

The method of claim 1, wherein the sample is preserved by one or more preservatives.

### Claim 11 (depends on 1)

The method of claim 1, wherein the spacers have different pre-determined heights.

### Claim 12 (depends on 1)

The method of claim 1, wherein the one or both of the plates comprise one or more vent holes that connect the inner surface to the outer surface of the respective plate, and the one or more vents are configured to facilitate the vaporization of the vaporizable components in the layer of the sample.

### Claim 13 (depends on 1)

The method of claim 1, wherein the one or both of the plates further comprises one or more structural features comprising micro- or nanostructures, or elements, wherein the one or more structural features are configured for lysing, temperature manipulation, biomaterial extraction, component separation, or a combination thereof.

### Claim 14 (depends on 1)

The method of claim 1, wherein the one or both of the plates further comprise one or more processing reagents at an inner surface thereof;
wherein the one or more processing reagents are configured for a sample treatment; and
wherein the sample treatment comprises cell lysis, staining, dehydration, phosphatase inhibition, or a combination thereof.

### Claim 15 (depends on 14)

The method of claim 14, wherein the one or both of the plates further comprise one or more trenches inside the sample contact area; and the one or more processing reagents are contained in the one or more trenches.

### Claim 16 (depends on 1)

The method of claim 1, wherein the one or both of the two plates further comprise one or more testing reagents at an inner surface thereof, and wherein the one or more testing reagents are configured for performing an assay on the sample.

### Claim 17 (depends on 16)

The method of claim 16, wherein the assay comprises an immunoassay or an enzyme activity assay.

### Claim 18 (depends on 1)

The method of claim 1, wherein the sample contains an analyte and the analyte is a nucleic acid.

### Claim 19 (depends on 1)

The method of claim 1, further comprising measuring an area or volume comprising a portion of the sample,
wherein the measuring comprises:
(i) having visual markers on the first plate, the second plate, between them, or any combination of thereof, wherein the visual marks aids the volume quantification of the sample collected in the device,
(ii) taking a 2D (two-dimensional)/3D (three-dimensional image of the sample, wherein the image is taken multiple times at different viewing angles, different wavelengths, different phases, and/or different polarization; and
(iii) image processing based on the visual maker and the image.

### Claim 20 (depends on 1)

The method of claim 1, wherein the imaging comprises light interference, or optical imaging a 2D (two-dimensional) or 3D (three-dimensional) imaging, optical imaging of multiple times, image processing, or any combination of thereof; wherein the optical imaging of multiple times uses different viewing angles, different wavelength, different phase, and/or different polarization.

### Claim 21 (depends on 1)

The method of claim 1, wherein the sample comprises blood, saliva, exhaled breath condensate, or urine.

### Claim 22 (depends on 1)

The method of claim 1, wherein the one or more processing reagents are configured for sample treatment, and the sample treatment comprises cell lysis, staining, dehydration, phosphatase inhibition, or a combination thereof.

### Claim 23 (depends on 1)

The method of claim 1, further comprising:
(1) cutting out a part of the layer, wherein the layer has a predetermined lateral area and a predetermined volume to obtain a cut-out part; and
(2) obtaining the sample inside the cut-out part,
wherein the predetermined volume is determined by multiplying the predetermined lateral area and the thickness of the spacers.

### Claim 24 (depends on 1)

The method of claim 1 further comprising: measuring a lateral area of the layer, and estimating the volume of the layer by multiplying the lateral area thereof and the height of the spacers.

### Claim 25 (depends on 1)

The method of claim 1, wherein one of the plates is flexible, and the thickness of the flexible plate times the Young's modulus of the flexible plate is in the range of 60 to 750 GPa-μm.

### Claim 26 (depends on 1)

The method of claim 1, wherein one of the two plates is flexible,
the thickness of the flexible plate times the Young's modulus of the flexible plate is in the range 60 to 750 GPa-μm, and
the fourth power of an inter-spacer-distance (ISD) of the spacers divided by the thickness (h) and the Young's modulus (E) of the flexible plate (ISD4/(hE)) is 5×105 μm3/GPa or less.

### Claim 27 (depends on 26)

The method of claim 26, wherein the inter-spacer distance is in the range of 1 μm to 120 μm.

### Claim 28 (depends on 26)

The method of claim 26, wherein the inter-spacer distance is in the range of 1 μm to 200 μm.

### Claim 29 (depends on 26)

The method of claim 26, wherein the inter-spacer distance is in the range of 400 μm or less.

### Claim 30 (depends on 1)

The method of claim 1, wherein the analyte comprises one or more selected from the group consisting of proteins, peptides, nucleic acids, synthetic compounds, inorganic compounds, organic compounds, bacteria, virus, cells, tissues, or nanoparticles.

### Claim 31 (depends on 1)

The method of claim 1 further comprising a step of quantification of a sample volume, wherein the quantification removes a none-sample-volume that is caused by spacers, air bubbles, dusts, or any combinations thereof.

### Claim 32 (depends on 1)

The method of claim 1, wherein the spacers have a periodic arrangement.

### Claim 33 (depends on 1)

The method of claim 1, wherein the reagent comprises a preservative that stabilizes nucleic acids.

### Claim 34 (depends on 1)

The method of claim 1, wherein one or both of the plates have location markers that are periodic spacers.

### Claim 35 (depends on 1)

The method of claim 1, wherein the sample comprises a diagnostic sample, an environmental sample, or a foodstuff sample.

### Claim 36 (depends on 1)

The method of claim 1, wherein the height of the spacers is 3 μm or less.

### Claim 37 (depends on 1)

The method of claim 1, wherein the height of the spacers is 10 μm or less.

### Claim 38 (depends on 1)

The method of claim 1, wherein the height of the spacers is in the range of 10 μm to 50 μm.