Methods, systems, and devices for detecting and identifying microorganisms in microbiological culture samples

• US 10,962,533 B2
• Filed: 11/27/2017
• Issued: 03/30/2021
• Est. Priority Date: 04/12/2012
• Status: Active Grant

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Weidemaier, Kristin, Carruthers, Erin Gooch, Curry, Adam C., Kuroda, Melody M. H., Lentz, Ammon David, Lizzi, Michael Justin, Fallows, Eric A., Gorelick, Donald E., Kessler, Jack, Lovette, Spencer, Ojala, Jeffrey S., Talmer, Mark A.
• Primary Examiner(s): Chin, Christopher L
• Application Number:
  US15/822,879
• Publication Number:
  US 20180136204A1
• Time in Patent Office: 1,219 Days
• Field of Search: None
• CPC Class Codes: B01L 2200/026 Fluid interfacing between devices or objects, e.g. connectors, inlet details
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 3/0217 of the plunger pump type medical syringes A61M
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 3/50825 Closing or opening means, corks, bungs closures for containers B65D; means for removing stoppers B67B7/02
• CPC Class Codes: B03C 1/01 by addition of magnetic adjuvants
• CPC Class Codes: B03C 1/288 disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 2201/26 for use in medical applications
• CPC Class Codes: C12M 23/08 Flask, bottle or test tube
• CPC Class Codes: C12M 23/22 Transparent or translucent parts glassware for laboratory use B01L3/00
• CPC Class Codes: C12M 23/38 Caps; Covers; Plugs; Pouring means
• CPC Class Codes: C12M 33/04 by injection or suction, e.g. using pipettes, syringes, needles pipettes in general B01L3/02
• CPC Class Codes: C12M 41/14 Incubators; Climatic chambers per se B01L1/00
• CPC Class Codes: C12M 41/36 of biomass, e.g. colony counters or by turbidity measurements electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404
• CPC Class Codes: G01N 33/54333 Modification of conditions of immunological binding reaction, e.g. use of more than one type of particle, use of chemical agents to improve binding, choice of incubation time or application of magnetic field during binding reaction
• CPC Class Codes: G01N 33/56911 Bacteria
• CPC Class Codes: G01N 35/0098 involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C

Abstract

Provided herein are methods, systems, and devices for detecting and/or identifying one or more specific microorganisms in a culture sample. Indicator particles, such as surface enhanced Raman spectroscopy (SERS)-active nanoparticles, each having associated therewith one or more specific binding members having an affinity for the one or more microorganisms of interest, can form a complex with specific microorganisms in the culture sample. Further, agitating magnetic capture particles also having associated therewith one or more specific binding members having an affinity for the one or more microorganisms of interest can be used to capture the microorganism-indicator particle complex and concentrate the complex in a localized area of an assay vessel for subsequent detection and identification. The complex can be dispersed, pelleted, and redispersed so that the culture sample can be retested a number of times during incubation so as to allow for real-time monitoring of the culture sample.

Claims

1. A system for automatically processing a plurality of sample tubes containing a culture sample, said system comprising:

an incubator for receiving the plurality of sample tubes therein and incubating the plurality of sample tubes at a predetermined temperature;

a first translational device coupled to the plurality of sample tubes and capable of moving the plurality of sample tubes to agitate the plurality of sample tubes, the first translational device further capable of moving the plurality of sample tubes from the incubator to a detection zone and agitating the plurality of sample tubes within the detection zone;

the detection zone comprising a pelleting/read assembly, the pelleting/read assembly comprising;

a magnet assembly for applying a magnetic field to the plurality of sample tubes within the detection zone to form a pellet in each of the plurality of sample tubes;

an optical device for interrogating each of the plurality of sample tubes within the detection zone to detect one or more microorganisms; and

a second translational device coupled to the optical device and capable of moving the optical device within the detection zone to interrogate the pellets.

2. The system according to claim 1, wherein the magnet assembly is capable of pivoting away from the plurality of sample tubes before interrogation by the optical device.

3. The system according to claim 1, wherein the system defines a plurality of thermal zones that can operate at different temperatures and contain one or more incubators.

4. The system according to claim 1 further comprising at least one heating element for heating the incubator.

5. The system according to claim 1, wherein the incubator is capable of receiving a tray for holding the plurality of sample tubes.

6. The system according to claim 5, wherein the first translation device is capable of oscillating the tray horizontally along an axis of the incubator.

7. The system according to claim 1, wherein the magnet assembly comprises a pair of longitudinal magnets spaced apart, and wherein the optical device comprises a read head extending between the pair of longitudinal magnets.

8. The system according to claim 1, wherein each of the plurality of sample tubes contains at least a sample, culture media, magnetic particles, and SERS particles, and wherein the SERS particles comprise a specific binding member for a microorganism.

9. The system according to claim 8, wherein the magnetic assembly is capable of forming at least one pellet comprising the microorganism bound to one or more of the SERS particles, and wherein the magnetic assembly comprises a slot through which the optical device is capable of interrogating the at least one pellet.

10. The system according to claim 1, wherein the magnetic assembly is capable of remaining adjacent to the plurality of sample tubes during pelleting by the magnet assembly and during interrogation by the optical device.