# US 10,871,491 B2 · Use of circulating cell biomarkers in the blood for detection and diagnosis of diseases and methods of isolating them > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,871,491 B2 - Document ID: US10871491B2 - Status: Granted - Kind: B2 - Application number: 15/506,439 - Filed: 2015-08-25 - Published: 2018-08-23 - Granted: 2020-12-22 - Earliest claimed: 2014-08-25 - Assignees: Creatv MicroTech, Inc. - Applicants: Creatv MicroTech, Inc. - Inventors: Cha-Mei Tang; Daniel Adams - Web page: https://patentgrep.com/patent/US10871491B2 ## CPC - G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells} - C12N 5/0694: {Cells of blood, e.g. leukemia cells, myeloma cells} - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - G01N 33/56983: {Viruses} - C12Q 2600/112: Disease subtyping, staging or classification - C12Q 2600/118: Prognosis of disease development - C12Q 2600/158: Expression markers - G01N 2800/085: Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## Abstract A new sensitive cell biomarker of solid tumors and viral infection is identified in blood. This biomarker can be used to determine presence of carcinomas, sarcomas, and viruses, rapid determination of treatment response, early detection of cancer, early detection of cancer recurrence, and may be used to determine therapy. ## Claims ### Claim 1 A method for confirming a diagnosis of cancer in a subject diagnosed with cancer, comprising detecting Cancer Associated Macrophage-Like cells (CAMLs) in a biological sample from the subject diagnosed with cancer, wherein said detecting comprises: (a) isolating intact cells of between about 20 microns to about 300 microns from the biological sample obtained from the subject using a microfilter having pores of about 15-20 microns in size, wherein the biological sample is one or more of peripheral blood, blood, lymph nodes, bone marrow, cerebral spinal fluid, tissue, or urine; and (b) selecting cells isolated in (a) having the following characteristics: (i) multiple individual nuclei and/or large fused nucleoli having a size of about 14-64 pm diameter; (ii) morphological shape selected from the group consisting of spindle, tadpole, round, oblong, and amorphous; and (iii) expression of one or more of the following markers: cytokeratin (CK) 8, CK18, CK19, vimentin, Cluster of differentiation (CD) 45, CD11c, CD 14, CD 146, CD202b, or CD31, wherein antibodies are used to select cells expressing the one or more markers, thereby detecting CAMLs in a biological sample from a subject, wherein when CAMLs are detected in the biological sample, the diagnosis of cancer is confirmed in the subject. ### Claim 2 (depends on 1) The method of claim 1, wherein the initial cancer diagnosis was via mammography, prostate-specific antigen (PSA) test, the presence of Cancer Antigen 125 (CA125), computed tomography (CT), magnetic resonance imaging (MRI) or positron-emission tomography (PET) imaging. ### Claim 3 (depends on 1) The method of claim 1, further comprising administering an anti-cancer therapeutic to the subject when diagnosis of cancer is confirmed in the subject. ### Claim 4 (depends on 1) The method of claim 1, wherein the microfilter has precision pore geometry and uniform pore distribution. ### Claim 5 (depends on 1) The method of claim 1, wherein CAMLs are detected using a microfiltration assay. ### Claim 6 (depends on 1) The method of claim 1, wherein the cancer is a solid tumor. ### Claim 7 (depends on 1) The method of claim 1, wherein the cancer is Stage I, Stage II, Stage III, or Stage IV cancer. ### Claim 8 (depends on 1) The method of claim 1, further comprising visualizing CAMLs by immuno-fluorescent staining. ### Claim 9 (depends on 1) The method of claim 1, further comprising visualizing CAMLs by colorimetric staining. ### Claim 10 (depends on 1) The method of claim 1, wherein molecular analysis of CAMLs is performed after diagnosis of cancer. ### Claim 11 (depends on 1) The method of claim 1, wherein the CAML size and number supports cancer staging. ### Claim 12 (depends on 1) The method of claim 1, further comprising detecting circulating tumor cells (CTCs) and/or white blood cells (WBCs) bound to CTCs in the biological sample, wherein CTCs and/or WBCs bound to CTCs are detected using a microfilter having a pore size of about 5-10 microns, and wherein when CTCs and/or WBCs bound to CTCs are detected in the biological sample, the diagnosis of cancer is further confirmed in the subject. ### Claim 13 (depends on 12) The method of claim 12, wherein the microfilter for use in detecting CTCs and/or WBCs bound to CTCs has a pore size of about 7-8 microns. ### Claim 14 (depends on 1) The method of claim 1, further comprising determining the identity of the cancer via staining said CAMLs for selected cancer markers. ### Claim 15 (depends on 14) The method of claim 14, wherein the staining further comprises quenching and re-staining the same cells for additional cancer markers.