Granted Patent
B2
US 12,275,010 · App. 18/340,633 · Granted Apr 15, 2025
Methods and devices for detection of multiple analytes from a biological sample
Inventors:
Rajaram Krishnan (San Diego, CA); Juan Pablo Hinestrosa Salazar (San Diego, CA); Robert Paul Turner (San Diego, CA); David Joseph Searson (San Diego, CA); James Gregory Madsen (San Diego, CA); Robert Kovelman (La Jolla, CA)
Assignee:
Xzom, Inc.
View Patent ↗
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Abstract
The present invention includes methods, devices and systems for isolating, identifying, analyzing, and quantifying biological materials from fluid samples. In various aspects, the methods, devices and systems may allow for a rapid procedure that requires a minimal amount of material and/or results in high purity biological materials from complex fluids such as blood, serum, or plasma.
Claims (22)
1. A method for analyzing a biological sample comprising:
a) capturing a plurality of analytes in the biological sample using an electrode configured to generate an AC dielectrophoretic field, wherein the plurality of analytes comprises at least two types of analytes comprising DNA, RNA, nucleosomes, exosomes, extracellular vesicles, proteins, or cellular vesicles; and
b) quantifying the at least two types of analytes of the plurality of analytes, wherein an analyte of the plurality of analytes is selected from the group consisting of tumor markers, cardiac markers, anemia markers, metabolic markers, kidney markers, diabetes markers, thyroid hormone markers, reproductive hormone markers and combinations thereof.
2. The method of claim 1 , wherein the capturing the plurality of analytes in the biological sample comprises using electrodes configured to generate a dielectrophoretic low field region and a dielectrophoretic high field region.
3. The method of claim 2 , wherein capturing the plurality of analytes in the biological sample comprises preferentially capturing a first analyte using a first electrode and a second analyte using a second electrode.
4. The method of claim 2 , wherein capturing the plurality of analytes in the biological sample comprises capturing more than one analyte on the same electrode.
5. The method of claim 1 , wherein the DNA comprises cell-free DNA.
6. The method of claim 1 , wherein quantifying the plurality of analytes comprises quantifying at least two different species of DNA, RNA, nucleosomes, exosomes, extracellular vesicles, proteins, cell membrane fragments, mitochondria, or cellular vesicles.
7. The method of claim 6 , wherein the method performance is characterized by an area under the receiver operating characteristic (ROC) curve (AUC) ranging from 0.60 to 0.70, 0.70 to 0.79, 0.80 to 0.89, or 0.90 to 1.00.
8. The method of claim 1 , wherein the biological sample is obtained from a subject.
9. The method of claim 8 , wherein the biological sample comprises a bodily fluid, blood, serum, plasma, urine, saliva, cells, tissue, or a combination thereof.
10. The method of claim 9 , wherein the biological sample comprises cells and the method further comprises lysing the cells.
11. The method of claim 9 , further comprising detecting a disease or condition in the subject using the at least two types of analytes quantified in the biological sample.
12. The method of claim 11 , wherein the disease or condition is cancer.
13. The method of claim 12 , wherein detecting further comprises determining a type of cancer, a stage of cancer, an increase in tumor burden relative to an earlier time point, a decrease in tumor burden relative to an earlier time point, no change in tumor burden relative to an earlier time point, or the efficacy of a cancer therapy, or the absence of cancer.
14. The method of claim 1 , wherein the quantifying comprises contacting an analyte of the plurality of analytes with an antibody that specifically binds to an analyte.
15. The method of claim 1 , wherein an analyte of the plurality of analytes is selected from the group consisting of PD-L1, CA19.9, CA125, GPC-1, CEA, CA 15.3, Prolactin, Ki-67, estrogen receptor alpha, CD30, CD30L, CD10, Alpha-fetoprotein, survivin, prostate-specific antigen, AZU1, beta-human chorionic gonadotropin, and CYFRA-21.
16. The method of claim 1 , wherein the quantifying comprises contacting an analyte of the plurality of analytes with an oligonucleotide, an intercalating dye, a dye that preferentially binds to a major groove, or a dye that preferentially binds to a minor groove.
17. The method of claim 1 , wherein the plurality of analytes comprises at least one of DNA and RNA and wherein the method further comprises amplifying at least one of the DNA or RNA by polymerase chain reaction or sequencing the at least one of the DNA and RNA.
18. The method of claim 1 , wherein quantifying comprises at least one of the group consisting of Quantitative Real Time PCR, enzyme-linked immunosorbent assay (ELISA), direct SYBR gold assay, direct PicoGreen assay, loss of heterozygosity (LOH) of microsatellite marker assay, electrophoresis, methylation analysis, MALDI-TOF, PCR, and digital PCR.
19. The method of claim 1 , further comprising eluting the analytes from the electrode after the capturing.
20. The method of claim 2 , wherein the dielectrophoretic low field region is produced using an alternating current having a voltage of 1 volt to 40 volts peak-peak; and/or a frequency of 5 Hz to 5,000,000 Hz and/or wherein the dielectrophoretic high field region is produced using an alternating current having a voltage of 1 volt to 40 volts peak-peak; and/or a frequency of 5 Hz to 5,000,000 Hz.
Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 25, 2025
From: BIOLOGICAL DYNAMICS, INC.
To: BIOLOGICAL LIQUIDATION, LLC
Reel/Frame 070321/0081 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 25, 2025
From: BIOLOGICAL LIQUIDATION, LLC
To: JACOBS FAMILY TRUST
Reel/Frame 070321/0433 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 25, 2025
From: JACOBS FAMILY TRUST
To: XZOM, INC.
Reel/Frame 070321/0880 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 26, 2023
From: KRISHNAN, RAJARAM; HINESTROSA SALAZAR, JUAN PABLO; TURNER, ROBERT PAUL; SEARSON, DAVID JOSEPH; MADSEN, JAMES GREGORY; KOVELMAN, ROBERT
To: BIOLOGICAL DYNAMICS, INC.
Reel/Frame 064111/0514 →
Continuity (3)
Continuation
16955707
Provisional Application
62607873
· Dec 19, 2017
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