Dilution calibration

Patent metadata

Field	Value
Publication number	US-11280706-B2
Application number	US-201816051650-A
Country	US
Kind code	B2
Filing date	Aug 1, 2018
Priority date	Aug 1, 2017
Publication date	Mar 22, 2022
Grant date	Mar 22, 2022

Abstract

The present disclosure provides devices, systems, and methods, for performing biological and chemical assays.

First claim

What is claimed is:

1. A method of dilution calibration and sample analysis, comprising:
providing an initial sample containing a calibration marker and suspected of containing an analyte, wherein the calibration marker has a first concentration with a known preset value;
diluting the initial sample with an unknown volume of a diluent to form a diluted sample;
using an assay device to obtain a second concentration of the calibration marker and analyzing the analyte in the diluted sample; and
determining a dilution factor for the diluted sample by comparing the first concentration and the second concentration, and calibrating the analysis of the analyte based on the dilution factor.

2. The method of claim 1 , wherein the preset value is an estimated normal value, which is different from a true value of the first concentration by less than 30%.

3. The method of claim 1 , further comprising obtaining the first concentration of the calibration marker in the initial sample.

4. The method of claim 3 , wherein the obtaining is performed using a first set of the assay device, and the step (iv) of obtaining and analyzing is performed using a second set of the assay device, and wherein the two sets of the assay device are of the same type.

5. The method of claim 1 , wherein the assay device comprises a QMAX device that comprises:
a first plate, a second plate, and spacers, wherein:
i. the plates are movable relative to each other into different configurations;
ii. each of the plates has, on its respective surface, a sample contact area for contacting a sample suspected of containing an analyte; and
iii. one or both of the plates comprise spacers that are fixed with a respective plate, wherein the spacers have a predetermined substantially uniform height and a predetermined constant inter-spacer distance and wherein at least one of the spacers is inside the sample contact area;

wherein one of the configurations is an open configuration, in which: the two plates are separated apart, the spacing between the plates is not regulated by the spacers, and the sample is deposited on one or both of the plates; and
wherein another of the configurations is a closed configuration which is configured after the sample deposition in the open configuration; and in the closed configuration: at least part of the sample is compressed by the two plates into a layer of uniform thickness, wherein the uniform thickness of the layer is confined by the inner surfaces of the two plates and is regulated by the plates and the spacers, and has an average thickness.

6. The method of claim 5 , wherein for a flexible plate, the thickness of the flexible plate times the Young's modulus of the flexible plate is in the range 60 to 750 GPa-um.

7. The method of claim 5 , wherein for a flexible plate, the fourth power of the inter-spacer-distance (ISD) divided by the thickness of the flexible plate (h) and the Young's modulus (E) of the flexible plate, ISD4/(hE), is equal to or less than 106 um3/GPa.

8. The method of claim 5 , wherein one or both plates comprises a location marker, either on a surface of or inside the plate, that provide information of a location of the plate.

9. The method of claim 5 , wherein one or both plates comprises a scale marker, either on a surface of or inside the plate, that provide information of a lateral dimension of a structure of the sample and/or the plate.

10. The method of claim 5 , wherein one or both plates comprises an imaging marker, either on surface of or inside the plate, that assists an imaging of the sample.

11. The method of claim 5 , wherein the average thickness of the layer of uniform thickness is in the range of 2 μm to 2.2 μm, 2.2 μm to 2.6 μm, 1.8 μm to 2 μm, or 2.6 μm to 3.8 μm, and the sample is blood.

12. The method of claim 5 , wherein the average thickness of the layer of uniform thickness is about equal to a minimum dimension of an analyte in the sample.

13. The method of claim 5 , wherein the inter-spacer distance is in the range of 7 μm to 50 μm, 50 μm to 120 μm, or 120 μm to 200 μm.

14. The method of claim 5 , wherein the inter-spacer distance is substantially periodic.

15. The method of claim 5 , wherein the spacers are pillars with a cross-sectional shape selected from the group consisting of: round, polygonal, circular, square, rectangular, oval, elliptical, or any combination of the same.

16. The method of claim 5 , wherein each spacer has the ratio of the lateral dimension of the spacer to its height is at least 1.

17. The method of claim 5 , wherein the minimum lateral dimension of spacer is in the range of 0.5 μm to 100 μm, or 0.5 μm to 10 μm.

18. The method of claim 5 , wherein the pressing of the QMAX device is by a human hand.

19. The method of claim 5 , wherein the spacers of the QMAX device have a pillar shape, a substantially flat top surface, a predetermined substantially uniform height, and a predetermined constant inter-spacer distance that is at least about 2 times larger than the size of the analyte, wherein the Young's modulus of the spacers times the filling factor of the spacers is equal or larger than 2 MPa, wherein the filling factor is the ratio of the spacer contact area to the total plate area, and wherein, for each spacer, the ratio of the lateral dimension of the spacer to its height is at least 1 (one).

20. The method of claim 5 , wherein the spacers of the QMAX device have a pillar shape, a substantially flat top surface, a predetermined substantially uniform height, and a predetermined constant inter-spacer distance that is at least about 2 times larger than the size of the analyte, wherein the Young's modulus of the spacers times the filling factor of the spacers is equal or larger than 2 MPa, wherein the filling factor is the ratio of the spacer contact area to the total plate area, and wherein, for each spacer, the ratio of the lateral dimension of the spacer to its height is at least 1 (one), wherein the fourth power of the inter-spacer-distance (ISD) divided by the thickness (h) and the Young's modulus (E) of the flexible plate (ISD{circumflex over ( )}4/(hE)) is 5×10{circumflex over ( )}6 um{circumflex over ( )}3/GPa or less.

21. The method of claim 5 , wherein the ratio of the inter-spacer distance of the spacers of the QMAX device to the average width of the spacers is 2 or larger, and the filling factor of the spacers multiplied by the Young's modulus of the spacers is 2 MPa or larger.

22. The method of claim 5 , wherein the analytes are the analyte in the detection of proteins, peptides, nucleic acids, synthetic compounds, and inorganic compounds.

23. The method of claim 5 , wherein the sample is a biological sample selected from amniotic fluid, aqueous humour, biopsy, blood, bone, breast milk, breath, cancerous sample, cartilage, cavity fluids, cerebrospinal fluid (CSF), cerumen (earwax), chime, chyle, connective tissue, cord blood, earwax, endolymph, epithelial tissue, exhaled breath condensates, exhaled condensate nasopharyngeal wash, feces, finger nail, fractionated blood, gastric acid, gastric fluid, gastric juice, glandular secretion, hair, interstitial fluids derived from tumorous tissue, lymph, lymphatic fluids, meconium, microbiota, mucus, muscle tissue, nasal drainage, nasal swab, nasopharyngeal wash, nervous tissue, ocular fluids, oil, pericardial fluid, perilymph, peritoneal fluid, phlegm, placental fluid, plasma, pleural fluid, pus, rheum, saliva, sebum, semen, serum, skin, spinal fluid, sputu

Assignees

• Essenlix Corp

Inventors

• Chou Stephen Y
• Ding Wei

Classifications

• G01N1/38 Primary

  Diluting, dispersing or mixing samples · CPC title

• G01N1/2813 Primary

  Producing thin layers of samples on a substrate, e.g. smearing, spinning-on (G01N1/30 takes precedence) · CPC title

• B01L2300/0822

  Slides · CPC title

• G01N35/00029

  provided with flat sample substrates, e.g. slides (G01N35/028 takes precedence) · CPC title

• B01L3/5027

  by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip · CPC title