Electrochemical detection of bacterial and/or fungal infections

• US 10,669,592 B2
• Filed: 02/26/2019
• Issued: 06/02/2020
• Est. Priority Date: 08/24/2017
• Status: Active Grant

• Current Assignee: Roche Molecular Systems Inc (Roche Holding AG)
• Original Assignee: Clinical Micro Sensors Inc. (Roche Holding AG)
• Inventors: Freeman-Cook, Lisa Lynn, Shaw, Christine J., Martinez, Milena Iacobelli, Al-Khouri, Anna Maria, Brown, Bradley Adam, Harvey, John Jay
• Primary Examiner(s): Priest, Aaron A
• Application Number:
  US16/286,476
• Publication Number:
  US 20190185915A1
• Time in Patent Office: 462 Days
• Field of Search: None
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 3/5023 with a sample being transported to, and subsequently stored in an absorbent for analysis
• CPC Class Codes: B01L 3/5027 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 B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: C12Q 1/6848 characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• CPC Class Codes: C12Q 1/6853 using modified primers or templates
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 1/689 for bacteria
• CPC Class Codes: C12Q 1/6895 for plants, fungi or algae
• CPC Class Codes: C12Q 2527/143 Concentration of primer or probe
• CPC Class Codes: C12Q 2531/113 PCR
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: G01N 27/3277 being a redox reaction, e.g. detection by cyclic voltammetry voltammetry per se G01N27/42, G01N27/48
• CPC Class Codes: G01N 27/48 using polarography, i.e. measuring changes in current under a slowly-varying voltage
• CPC Class Codes: G16H 10/40 for data related to laboratory analysis, e.g. patient specimen analysis
• CPC Class Codes: G16H 15/00 ICT specially adapted for medical reports, e.g. generation or transmission thereof
• CPC Class Codes: G16H 80/00 ICT specially adapted for facilitating communication between medical practitioners or patients, e.g. for collaborative diagnosis, therapy or health monitoring
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

The present disclosure relates to methods and devices for amplifying a plurality of targets in a single PCR run while distinguishing between clinically relevant amplification and amplification from other sources such as from background contamination. The methods and devices further enable discrimination between gram-positive, gram-negative and fungal infections as wells as identify antimicrobial resistance genes. When applying the methods and devices of the invention, the species or genus of an infection(s), and genus of a fungal co-infection(s) or category of bacterial (gram-positive or negative) co-infection(s) are identified. Species identification of co-infections can also be achieved. Further, when applying the methods and devices of the invention, organisms which are likely to be contaminating organisms from a blood draw are identified.

Claims

1. A method for processing at least a first and second patient sample comprising:

a) receiving a first and second patient sample;

b) receiving a test order from a hospital laboratory information system (LIS) for the first and second patient sample;

c) processing the first and second patient sample in a target analyte detection instrument wherein the target analyte detection instrument is directly linked to a LIS interchange;

d) generating a first result identifying at least one pathogen in the first patient sample processed by the target analyte detection instrument and generating a second result identifying at least one value for the second patient sample processed by the target analyte detection instrument; and

e) automatically reporting the first result to the LIS interchange by the target analyte detection instrument directly to the LIS interchange and queuing the second result on the target analyte detection instrument for manual reporting based on the at least one value of the second result.

2. The method of claim 1, wherein the at least one value of the second result is an invalid result caused by an instrument error or a detection error.

3. The method of claim 1, wherein the at least one value of the second result is an invalid result caused by three or more targets being detected in the second patient sample.

4. The method of claim 1, wherein the LIS interchange connects to more than one hospital LIS.

5. The method of claim 1, wherein the at least one pathogen in the first patient sample processed is a viable gram-positive bacteria and the first patient sample comprises viable gram-positive bacteria and non-viable gram-positive bacteria.

6. The method of claim 5, wherein the target analyte detection instrument performs a single detuned multiplex end-point polymerase chain reaction (PCR) on the first patient sample, the PCR comprising about 30 to about 35 cycles.

21. The method of claim 1, wherein the LIS interchange automatically reports the first result to the hospital LIS.

7. A method for processing at least a first and second patient sample comprising:

a) receiving a first and second patient sample;

b) receiving a test order from a hospital LIS;

c) processing the first and second patient sample according to the test order, in a target analyte detection instrument wherein the target analyte detection instrument is directly linked to a LB interchange;

d) generating a first result by the target analyte detection instrument that identifies at least one pathogen in the first patient sample and generating a second result from the target analyte detection instrument that identifies at least one value for the second patient sample processed;

e) converting the first result to a first detection report and converting the second result to a second detection report; and

f) automatically reporting by the target analyte detection instrument the first detection report to the LB interchange and queuing the second detection result on the target analyte detection instrument for manual reporting based on the at least one value of the second result.

8. The method of claim 7, further comprising manually applying comments to the first detection report.

9. The method of claim 7, further comprising manually applying comments to the second detection report.

22. The method of claim 7, wherein the LIS interchange automatically reports the first detection report to the hospital LIS.

10. A method for processing at least a first and second patient sample comprising:

a) receiving a first and second patient sample;

b) receiving a test order from a hospital LIS;

c) processing the first and second patient sample in a target analyte detection instrument wherein the target analyte detection instrument is directly linked to a LIS interchange;

d) generating a first detection report identifying at least one pathogen in the first patient sample processed by the target analyte detection instrument and generating a second detection report identifying at least one value for the second patient sample processed by the target analyte detection instrument;

e) automatically sending the first detection report by the target analyte detection instrument to the LIS interchange and queuing the second detection report on the target analyte detection instrument for manual reporting based on the at least one value of the second result;

f) converting the first detection report to a first physician test result report; and

g) reporting the first physician test result report to a hospital LIS using the LIS interchange.

11. The method of claim 10, wherein the first detection report is in a CSV format and the first physician test result report is in an HL7 or ASTM format.

12. The method of claim 10, wherein the at least one pathogen in the first patient sample is a blood stream pathogen that causes or is suspected of causing sepsis.

13. The method of claim 10, wherein the physician test order is converted from an HL7 or ASTM format to a CSV format.

14. The method of claim 10, wherein the second detection report identifies at least one pathogen as Propionibacterium acnes, Staphylococcus epidermidis, Micrococcus, Lactobacillus or Corynebacterium.

15. The method of claim 10, wherein the first detection report identifies the presence of a resistance gene present in the at least one pathogen in the first patient sample.

16. The method of claim 10, wherein the at least one pathogen is a human pathogen, and wherein the first patient sample further comprises a contaminating pathogen.

17. The method of claim 10, wherein the first physician test result report comprises information on detected targets, non-detected targets, invalid results and/or control data.

18. The method of claim 10, wherein the first detection report comprises information on detected targets, non-detected targets, invalid results and/or control data.

19. The method of claim 10, wherein the target analyte detection instrument sends an alert if stability time is violated for the first patient sample.

20. The method of claim 19, wherein the target analyte detection instrument performs a single detuned multiplex end-point polymerase chain reaction (PCR) on the first patient sample, the PCR comprising about 30 to about 35 cycles.