Systems and methods for detecting infectious diseases

Patent metadata

Field	Value
Publication number	US-10283217-B2
Application number	US-201514789904-A
Country	US
Kind code	B2
Filing date	Jul 1, 2015
Priority date	Sep 6, 2013
Publication date	May 7, 2019
Grant date	May 7, 2019

Abstract

Systems, methods, and devices for detecting infections in a clinical sample are provided. Small-volume clinical samples obtained at a point-of-service (POS) location and may be tested at the POS location for multiple markers for multiple diseases, including upper and lower respiratory diseases. Samples may be tested for cytokines, or for inflammation indicators. Dilution of samples, or levels of detection, may be determined by the condition or past history of a subject. Test results may be obtained within a short amount of time after sample placement in a testing device, or within a short amount of time after being obtained from the subject. A prescription for treatment of a detected disorder may be provided, and may be filled, at the POS location. A bill may be automatically generated for the testing, or for the prescription, may be automatically sent to an insurance provider, and payment may be automatically obtained.

First claim

What is claimed is:

1. A method of detecting the presence of at least three disease markers comprising:
a) introducing a sample and a swab sample obtained by a swab into an automatic sample processing device, wherein said automatic sample processing device is configured to perform nucleic acid assays, immunoassays, and cytometric assays,
wherein said sample is contained in a cartridge containing all reagents required for the performance of said nucleic acid assays, immunoassays, and cytometric assays, said cartridge being configured to hold the sample and the swab sample,
wherein said automatic sample processing device comprises:
i) a sample handling system;
ii) at least one detector; and
iii) a cytometry station comprising an imaging aevice ana a stage for receiving a microscopy cuvette;

b) transferring a portion of the sample to a nucleic acid assay unit, an immunoassay assay unit, and the microscopy cuvette with the aid of the sample handling system;
c) performing an assay selected from one of a nucleic acid assay and an immunoassay, for the detection of at least one disease marker in the sample, or an aliquot thereof;
d) obtaining an image of the sample, or an aliquot thereof, with said cytometry station for detecting the presence of at least one disease marker in the sample, or in an aliquot thereof; and
e) performing another assay selected from one of a nucleic acid assay and an immunoassay, for the detection of at least another disease marker in the swab sample, or an aliquot thereof.

2. The method of claim 1 , wherein the method is a point-of service (POS) method performed at a POS location.

3. The method of claim 1 , wherein said assays are performed in less than about 40 minutes.

4. The method of claim 1 , wherein said detecting the presence of at least three disease markers in the sample, or an aliquot or aliquots thereof comprises detecting at least one disease marker using a cytometry station, and detecting at least two disease markers using a detector.

5. The method of claim 1 , comprising detecting the presence of a nucleic acid disease marker, a protein disease marker, and a cell morphology disease marker in the sample, or in an aliquot or aliquots thereof.

6. The method of claim 1 , wherein said nucleic acid assay comprises isothermal nucleic acid amplification methods comprising non-cycling nucleic acid amplification methods,
wherein said non-cycling nucleic acid amplification methods comprise contacting at least a portion of a sample with a first primer and a second primer, wherein:
said first primer comprises a first tail region and a first template-binding region, wherein said first template-binding region is complementary to at least a first portion of said target nucleic acid, and
said second primer comprises a second tail region and a second template-binding region, wherein said second template-binding region is complementary to at least a second portion of said target nucleic acid,
wherein at least portions of said first and second tail regions are complementary to each other; and
wherein said first and second tail regions of said first primer and of said second primer each comprise a) a 5′ terminal nucleotide of the primer, b) an innermost nucleotide, wherein the innermost nucleotide is downstream from the 5′ terminal nucleotide, and c) a middle section comprising one or more nucleotides between the 5′ terminal nucleotide and the innermost nucleotide.

7. The method of claim 1 , wherein at least one disease marker is a marker for inflammation, and at least one disease marker is a marker for a disease-causing agent.

8. The method of claim 1 , wherein at least one disease marker is a marker for a disease selected from influenza, a respiratory disease, a sexually transmitted disease, and another infectious disease.

9. The method of claim 1 , further comprising a sample obtained from a subject using a swab.

10. The method of claim 1 , wherein at least one disease marker is a marker indicative of a sexually transmitted disease selected from a disease caused by herpes simplex-1 virus (HSV-1), herpes simplex-2 virus (HSV-2), human immunodeficiency virus (HIV), HIV-2 Group A, HIV-2 Group B, HIV-1 Group M, Hepatitis B, Hepatitis Delta, herpes simplex virus (HSV), streptococcus B, and treponema pallidum.

11. The method of claim 1 , wherein transferring a portion of said sample comprises transferring the sample, or an aliquot thereof, by a fluid handling system comprising a pipette.

12. The method of claim 1 , wherein performing an assay comprises centrifugation of the sample, or an aliquot thereof.

13. The method of claim 1 , wherein performing an assay comprises separation of a blood sample into fractions to provide a serum fraction of the blood sample.

14. The method of claim 1 , wherein performing an assay comprises dilution of the sample.

15. The method of claim 1 , wherein said at least three disease markers comprise disease markers indicative a disease or diseases selected from the group of diseases consisting of Influenza A Matrix protein, Influenza H3N2, Influenza H1N1 seasonal, Influenza H1N1 novel, Influenza B, an Ebola virus, a Marburg virus, a Cueva virus, Streptococcus pyogenes (A), Mycobacterium Tuberculosis, Staphylococcus aureus (MR), Staphylococcus aureus (RS), Bordetella pertussis (whooping cough), Streptococcus agalactiae (B), Influenza H5N1, Influenza H7N9, Adenovirus B, Adenovirus C, Adenovirus E, Hepatitis b, Hepatitis c, Hepatitis delta, Treponema pallidum , HSV-1, HSV-2, HIV-1, HIV-2, Dengue 1, Dengue 2, Dengue 3, Dengue 4, Malaria, West Nile Virus, Trypanosoma cruzi (Chagas), Klebsiella pneumoniae ( Enterobacteriaceae spp), Klebsiella pneumoniae carbapenemase (KPC), Epstein Barr Virus (mono), Rhinovirus, Parainfluenza virus (1), Parainfluenza virus (2), Parainfluenza virus (3), Parainfluenza virus (4a), Parainfluenza virus (4b), Respiratory syncytial virus (RSV) A, Respiratory syncytial virus (RSV) B, Coronavirus 229E, Coronavirus HKU1, Coronavirus OC43, Coronavirus NL63, Novel Coronavirus, Bocavirus, human metapneumovirus (HMPV), Streptococcus pneumoniae (penic R), Streptococcus pneumoniae (S), Mycoplasma pneumoniae, Chlamydia pneumoniae, Bordetella parpertussis, Haemophilus influenzae (ampic R), Haemophilus influenzae (ampic S), Moraxella catarrhalis, Pseudomonas spp ( aeruginosa ), Haemophilus parainfluenzae, Enterobacter cloacae ( Enterobacteriaceae spp), Enterobacter aerogenes ( Enterobacteriaceae spp), Serratia marcescens ( Enterobacteriaceae spp), Acinetobacter baumanii, Legionella spp, Escherichia coli, Candida, Chlamydia trachomatis , Human Papilloma Virus, Neisseria gonorrhoeae, plasmodium , and Trichomonas (vagin).

16. The method of claim 1 , wherein one of the at least three disease markers is a tuberculosis (Mycobacterium tuberculosis) marker.

17. The method of claim 1 , wherein one of the at least three disease markers is a marker for a Staphylococcus bacterium or for a Streptococcus bacterium.

18. The method of claim 1 , wherein one of the at least three disease markers is a marker for a virus selected from the group of viruses consisting of a filo virus, a Corona virus, West Nile Virus, Epstein-Barr Virus, and a Dengue Virus.

19. A method of detecting the presence of at least three disease markers comprising:
a) introducing a sample and a swab sample obtained by a swab into an automatic sample processing device, wherein said automatic sample processing device is configured to perform nucleic acid assays, immunoassays, and cytometric

Assignees

• Theranos Ip Co Llc

Inventors

• Lui Clarissa
• Holmes Elizabeth A
• Patel Pranav
• Tabakman Scott
• Belhocine Kamila
• Richardson Aaron
• Lee Josephine

Classifications

• G16H50/20

  for computer-aided diagnosis, e.g. based on medical expert systems · CPC title

• G01N33/56994

  Herpetoviridae, e.g. cytomegalovirus, Epstein-Barr virus · CPC title

• C12Q2600/16

  Primer sets for multiplex assays · CPC title

• C12Q1/6893

  for protozoa · CPC title

• G16H10/40 Primary

  for data related to laboratory analysis, e.g. patient specimen analysis · CPC title