High confidence in positive status determination

• US 10,337,046 B2
• Filed: 02/19/2008
• Issued: 07/02/2019
• Est. Priority Date: 02/19/2008
• Status: Active Grant

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Beaty, Patrick Shawn
• Primary Examiner(s): Lin, Jerry
• Application Number:
  US12/918,019
• Publication Number:
  US 20110029252A1
• Time in Patent Office: 4,151 Days
• Field of Search: 702 19
• CPC Class Codes: C12Q 1/04 Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor C12Q1/6897 takes precedence

Abstract

Systems, methods, and apparatus for determining whether a culture in a vessel contains a plurality of microorganisms are provided. A normalization relative value is calculated for each respective measurement of a biological state of the culture between (i) the respective measurement and (ii) an initial biological state. For each fixed interval of time points, a derivative of the normalization relative values in the interval of time points is calculated, thereby forming a plurality of rate transformation values. For each set of rate transformation values in the plurality of rate transformation values, a measure of central tendency of the values in the set is computed, thereby forming a plurality of average relative transformation values. A determination whether the culture contains the microorganisms is made based on whether any calculated average relative transformation value exceeds a first threshold or whether an extent of growth exhibited by the culture exceeds a second threshold.

Claims

1. A method comprising:

(A) incubating, with an incubator, a culture disposed within a vessel during portions of a time interval between a first time point and a second time point, wherein the culture comprises a sample and a culture media;

(B) measuring, with a sensor, a biological state of the culture at a plurality of time points between the first time point and the second time point, wherein the biological state is one of CO₂ concentration, O₂ concentration, pH, a rate of change in CO₂ concentration, a rate of change in O₂ concentration, or a rate of change in pH;

(C) determining, with one or more processors, a plurality of rate transformation values, wherein each rate transformation value is derived from a different subset of the measurements of the biological state of the culture within a predetermined time interval;

(D) determining, with the one or more processors, a plurality of average relative transformation values, wherein each average relative transformation value is derived from a different subset of the rate transformation values;

(E) determining, with the one or more processors, that the culture contains a plurality of microorganisms when (i) at least one average relative transformation value exceeds a first threshold value or (ii) an extent of growth exhibited by the culture exceeds a second threshold value, wherein the extent of growth is derived from one or more of the measurements of the biological state of the culture; and

(F) processing the vessel to confirm the presence of the plurality of microorganisms after it is determined in step (E) that the culture contains a plurality of microorganisms.

2. The method of claim 1, wherein processing the vessel to confirm the presence of the plurality of microorganisms in step (F) comprises at least one of (i) preparing a gram stain or (ii) preparing a subculture on a plated medium.

3. The method of claim 1 further comprising:

initiating processes for microorganism identification and antimicrobial susceptibility testing when it is confirmed in step (F) that the culture contains a plurality of microorganisms.

4. The method of claim 1 further comprising:

displaying the determination of step (E) on a user interface device.

5. The method of claim 1, wherein the sensor used in step (B) to measure the biological state of the culture at the plurality of time points is a fluorescent CO₂ sensor.

6. The method of claim 1, wherein each rate transformation value is a first derivative of a different subset of the measurements of the biological state of the culture within a predetermined time interval.

7. The method of claim 1, wherein the determination of step (E) is made when the at least one average relative transformation value exceeds the first threshold value.

8. The method of claim 1 further comprising:

converting the measurements of the biological state of the culture into normalization relative values.

9. The method of claim 8, wherein each rate transformation value is a first derivative of a different subset of the normalization relative values within a predetermined time interval.

10. The method of claim 9, wherein the determination of step (E) is made when the extent of growth exhibited by the culture exceeds the second threshold value.

11. The method of claim 10, wherein the extent of growth (EG) is determined by the equation:

EG=NR_{after_growth}−

NR_{minimum_growth},

wherein;

NR_{after_growth} is a normalization relative value in the plurality of normalization relative values that was used in the calculation of (i) a maximum average relative transformation value in the plurality of average relative transformation values, (ii) a first average relative transformation value following the maximum average relative transformation value, or (iii) a first average relative transformation value preceding the maximum average relative transformation value; and

NR_{minimum_growth} is a normalization relative value in the plurality of normalization relative values that was used in the calculation of a first average relative transformation value to achieve a third threshold value.

12. The method of claim 1, wherein the determination of step (E) is made when (i) the at least one average relative transformation value exceeds the first threshold value and (ii) the extent of growth exhibited by the culture exceeds the second threshold value.

13. The method of claim 1, wherein all of the predetermined time intervals have the same duration.

14. The method of claim 13, wherein the rate transformation values are calculated and stored in successive instances.

15. The method of claim 14, wherein the average relative transformation values are calculated and stored in successive instances.

16. An apparatus comprising:

(A) one or more processors;

(B) an incubator for incubating a culture disposed within a vessel during portions of a time interval between a first time point and a second time point, wherein the culture comprises a sample and a culture media;

(C) a sensor for measuring a biological state of the culture at a plurality of time points between the first time point and the second time point, wherein the biological state is one of CO₂ concentration, O₂ concentration, pH, a rate of change in CO₂ concentration, a rate of change in O₂ concentration, or a rate of change in pH; and

(D) a memory comprising;

(1) a first threshold value;

(2) a second threshold value; and

(3) a culture determination module comprising;

(a) electronically encoded instructions for determining a plurality of rate transformation values, wherein each rate transformation value is derived from a different subset of the measurements of the biological state of the culture within a predetermined time interval;

(b) electronically encoded instructions for determining a plurality of average relative transformation values, wherein each average relative transformation value is derived from a different subset of the rate transformation values; and

(c) electronically encoded instructions for determining that the culture contains a plurality of microorganisms when (i) at least one average relative transformation value exceeds the first threshold value or (ii) an extent of growth exhibited by the culture exceeds the second threshold value, wherein the extent of growth is derived from one or more of the measurements of the biological state of the culture; and

(E) a user interface configured to notify a user that the vessel should be processed to confirm the presence of the plurality of microorganisms after it is determined that the culture contains a plurality of microorganisms.

17. The apparatus of claim 16, wherein the user interface is configured to display the notification on a monitor.

18. The apparatus of claim 16, wherein the electronically encoded instructions (iii) determine that the culture contains a plurality of microorganisms when (i) the at least one average relative transformation value exceeds the first threshold value and (ii) the extent of growth exhibited by the culture exceeds the second threshold value.

19. The apparatus of claim 16, wherein the culture determination module further comprises electronically encoded instructions for converting the measurements of the biological state of the culture into normalization relative values.

20. The apparatus of claim 19, wherein each rate transformation value is a first derivative of a different subset of the normalization relative values within a predetermined time interval.