US-20260125734-A1 - SYSTEMS, DEVICES, AND METHODS FOR CONDUCTING ANTIMICROBIAL SUSCEPTIBILITY TESTING

US20260125734A1US 20260125734 A1US20260125734 A1US 20260125734A1US-20260125734-A1

Abstract

Various apparatus, systems, and methods for determining a susceptibility of a bacteria to an antibiotic are disclosed. In one aspect, a reader comprises at least one reader module configured to receive a well plate covered by a sensor array lid. Wells of the well plate contain aliquots of a sample comprising the bacteria. The wells also comprise test wells containing the antibiotic and at least one control well without the antibiotic. The reader module further comprises conductive connectors configured to contact conductive pads of the sensor array lid. One or more processors of the reader are programmed to determine the susceptibility of the bacteria to the antibiotic based on any changes in a solution characteristic of the aliquots within the test wells compared to the control well. The reader is also configured to perform certain internal quality checks when determining the susceptibility of the bacteria to the antibiotic.

Inventors

CREIGHTON T. BUIE
Andrew H. THEISS
Ankit BAINGANE
Tatiana LAM
Elizabeth Botbol PONTE
Kristen Lugenie COTNER
Nitin K. RAJAN
Oren S. KNOPFMACHER
Meike Herget
Suzanne PUTNEY

Assignees

AVAILS MEDICAL, INC.

Dates

Publication Date: 20260507
Application Date: 20251030

Claims (20)

1 . A reader for determining a susceptibility of a bacteria to an antibiotic, comprising: a plurality of reader modules, wherein each of the reader modules comprises: a plate tray configured to receive a well plate covered by a sensor array lid, wherein the well plate comprises a plurality of wells configured to contain aliquots of a sample comprising the bacteria, wherein the wells comprise test wells containing the antibiotic and at least one control well devoid of any antibiotic, and wherein the sensor array lid comprises a plurality of sensor units, a printed circuit board assembly (PCBA) disposed above the plate tray, wherein the PCBA comprises a plurality of conductive connectors configured to extend downward from an underside of the PCBA to contact conductive pads of the sensor array lid, wherein at least part of each of the sensor units is configured to be immersed in an aliquot of the sample within a well of the well plate, and one or more processors communicatively coupled to the PCBA, wherein the one or more processors are programmed to determine the susceptibility of the bacteria to the antibiotic based on any changes in a solution characteristic of the aliquots within the test wells compared to the control well over time.
2 . The reader of claim 1 , wherein the conductive connectors are leaf spring connectors.
3 . The reader of claim 2 , wherein the leaf spring connectors are made in part of a conductive metal or metal alloy.
4 . The reader of claim 1 , wherein each of the reader modules further comprises a gasket disposed in between the PCBA and the sensor array lid covering the well plate placed on the plate tray, wherein the gasket is configured to create a partial seal around a top of the sensor array lid to control an evaporation rate of the aliquots of the sample and to control a humidity level and a partial pressure of oxygen within a space above the well plate.
5 . The reader of claim 4 , wherein the gasket is made in part of a semipermeable polymeric material having a Shore A hardness of between about 20 to 55.
6 . The reader of claim 4 , wherein the gasket serves as a perimeter surrounding portions of the conductive connectors extending downward from the underside of the PCBA.
7 . The reader of claim 1 , wherein each of the reader modules further comprises an upper heater coupled to the PCBA, and wherein the upper heater is configured to control condensation on the conductive connectors by heating the conductive connectors above a dew point.
8 . The reader of claim 7 , wherein each of the reader modules further comprises a lower heater coupled to the plate tray, wherein the well plate is configured to be placed above the lower heater, wherein the lower heater is configured to heat the well plate.
9 . The reader of claim 8 , wherein each of the reader modules further comprises a first temperature sensor configured to monitor a temperature of the lower heater used to heat the well plate.
10 . The reader of claim 9 , wherein each of the reader modules further comprises a second temperature sensor and a humidity sensor to monitor the temperature and the humidity, respectively, within a space above the well plate.
11 . The reader of claim 1 , wherein the sensor units of the sensor array lid comprise oxidation-reduction potential (ORP) sensors, wherein the one or more processors are further programmed to perform an internal quality check, wherein the internal quality check comprises checking that a baseline voltage of a starting ORP of each of the aliquots of the sample within each of the wells is between about 2600 millivolts (mV) and 2750 mV.
12 . The reader of claim 1 , wherein the sensor units of the sensor array lid comprise oxidation-reduction potential (ORP) sensors, wherein the one or more processors are further programmed to perform an internal quality check, wherein the internal quality check comprises checking that a voltage noise of each of the ORP sensors is between about 0 millivolt root-mean-square (mVrms) and 5 mVrms.
13 . The reader of claim 1 , wherein the sensor units of the sensor array lid comprise oxidation-reduction potential (ORP) sensors, wherein the one or more processors are further programmed to perform an internal quality check, wherein the internal quality check comprises checking that a sensor voltage drift of each of the ORP sensors is between about 0 mV per hour and 40 mV per hour.
14 . The reader of claim 1 , further comprising a reader housing, wherein each of the reader modules further comprises a tray carrier configured to automatically translate or drive the plate tray at least partially out of the reader housing to receive the well plate covered by the sensor array lid, wherein the conductive connectors are aligned to contact the conductive pads of the sensor array lid after the plate tray loaded with the well plate covered by the sensor array lid is automatically retracted back into the reader housing by the tray carrier.
15 . The reader of claim 1 , wherein the sensor array lid further comprises a lid cover and a sensor substrate layer coupled to an underside of the lid cover, wherein the lid cover comprises a plurality of openings configured to expose the conductive pads, and wherein the conductive connectors are configured to extend into the openings to contact the conductive pads.
16 . A reader for determining a susceptibility of a bacteria to an antibiotic, comprising: a plurality of reader modules, wherein each of the reader modules comprises: a plate tray configured to receive a well plate covered by a sensor array lid, wherein the well plate comprises a plurality of wells configured to contain aliquots of a sample comprising the bacteria, wherein the wells comprise test wells containing the antibiotic and at least one control well devoid of any antibiotic, and wherein the sensor array lid comprises a plurality of sensor units, a printed circuit board assembly (PCBA) disposed above the plate tray and configured to be in electrical contact with the sensor array lid, wherein at least part of each of the sensor units of the sensor array lid is configured to be immersed in an aliquots of the sample within a well of the well plate, a gasket disposed in between the PCBA and the sensor array lid, wherein the gasket is configured to create a partial seal around a top of the sensor array lid to control an evaporation rate of the aliquots of the sample and a humidity level and a partial pressure of oxygen within a space above the well plate, and one or more processors communicatively coupled to the PCBA, wherein the one or more processors are programmed to determine the susceptibility of the bacteria to the antibiotic based on any changes in a solution characteristic of the aliquots within the test wells compared to the control well over time.
17 .- 31 . (canceled)
32 . A reader for determining a susceptibility of a bacteria to an antibiotic, comprising: a plurality of reader modules, wherein each of the reader modules comprises: a plate tray configured to receive a well plate covered by a sensor array lid, wherein the well plate comprises a plurality of wells configured to contain aliquots of a sample comprising the bacteria, wherein the wells comprise test wells containing the antibiotic and at least one control well devoid of any antibiotic, and wherein the sensor array lid comprises a plurality of oxidation-reduction potential (ORP) sensors, a printed circuit board assembly (PCBA) disposed above the plate tray and configured to be in electrical contact with the sensor array lid, wherein at least part of each of the ORP sensors is configured to be immersed in an aliquot of the sample within a well of the well plate, and one or more processors communicatively coupled to the PCBA, wherein the one or more processors are programmed to: check that a baseline voltage of a starting ORP of each of the aliquots of the sample within the wells is between about 2600 millivolts (mV) and 2750 mV, a voltage noise of each of the ORP sensors is between about 0 millivolt root-mean-square (mVrms) and 5 mVrms, and a sensor voltage drift of each of the ORP sensors is between about 0 mV per hour and 40 mV per hour, and determine the susceptibility of the bacteria to the antibiotic based on any changes in a solution characteristic of the aliquots within the test wells compared to the control well over time.
33 .- 41 . (canceled)
42 . One or more non-transitory computer-readable media comprising instructions stored thereon, that when executed by one or more processors, cause the one or more processors to perform operations comprising: checking that a baseline voltage of a starting oxidation-reduction potential (ORP) of each aliquot of a sample within wells of a well plate is between about 2600 millivolts (mV) and 2750 mV, wherein the sample comprises bacteria, wherein the wells comprise test wells containing an antibiotic and at least one control well devoid of any antibiotic, wherein the well plate is covered by a sensor array lid comprising a plurality of ORP sensors configured to be immersed in the aliquots of the sample within the well plate, wherein the well plate is placed on a plate tray of reader module, wherein the reader module further comprises a printed circuit board assembly (PCBA) disposed above the plate tray and configured to be in electrical contact with the sensor array lid; checking that a voltage noise of each of the ORP sensors is between about 0 millivolt root-mean-square (mVrms) and 5 mVrms; checking that a sensor voltage drift of each of the ORP sensors is between about 0 mV per hour and 40 mV per hour; and determining a susceptibility of the bacteria to the antibiotic based on any changes in a solution characteristic of the aliquots within the test wells compared to the control well over time.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63/715,378 filed on Nov. 1, 2024, the content of which is incorporated herein by reference in its entirety. STATEMENT AS TO FEDERALLY SPONSORED RESEARCH This invention was made with U.S. Government support under Agreement Number 75A50122C00028, awarded by the U.S. Department of Health and Human Services. The U.S. Government has certain rights in the invention. TECHNICAL FIELD The present disclosure relates generally to diagnostic testing and, more specifically, to systems, devices, and methods for conducting antimicrobial susceptibility testing. BACKGROUND An increasing number of pathogenic bacteria are acquiring antibiotic resistance and new forms of resistance are continuously emerging with alarming speed across international boundaries. The U.S. Center for Disease Control (CDC) considers antimicrobial resistance as one of the biggest public health challenges of our time. Every year in the U.S. alone, over 2 million people acquire antibiotic-resistant infections and death rates are continuously rising. Providing a rapid and low-cost antibiotic susceptibility test (AST) will be crucial in controlling this burgeoning problem. Current gold standard AST tests still often require burdensome and time-consuming overnight culturing steps. This has prompted a push for rapid AST tests that can provide results in a matter of hours. Speeding up AST results to provide targeted antibiotic therapy early on is key to improving patient survival. Delays in obtaining AST results can lead to healthcare professionals having no choice but to administer broad-spectrum antibiotics, which can promote antibiotic resistance (AR). While new technologies are under development, most still require a culture isolate as an input. Therefore, a solution is needed that can detect phenotypic bacterial growth in samples containing a patient's blood (e.g., a positive blood culture) that does not need to go through the bacterial isolation steps of traditional testing procedures. Such a solution should not be overly complex and should be cost-effective to manufacture. Such a solution should also not rely on labor-intensive techniques and provide accurate results. Such a solution should also allow for multiplex detection involving simultaneous readout of multiple wells to rapidly determine minimum inhibitory concentrations (MICs). SUMMARY Disclosed herein are systems, devices, and methods for conducting antimicrobial susceptibility testing. In some embodiments, a reader for determining the susceptibility of a bacteria to an antibiotic comprises a plurality of reader modules. Each of the reader modules can comprise a moveable or slidable plate tray configured to receive a well plate covered by a sensor array lid. Each of the reader modules can also comprise a printed circuit board assembly (PCBA) disposed above the plate tray when the plate tray is inserted or otherwise retracted into the reader. The well plate can comprise a plurality of wells configured to contain aliquots of a sample including the bacteria. The wells of the well plate can comprise test wells containing the antibiotic and at least one control well devoid of any antibiotic. The PCBA can comprise a plurality of conductive connectors. The conductive connectors can extend downward from an underside of the PCBA to contact conductive pads of the sensor array lid. Sensor units of the sensor array lid can be configured to be immersed in the aliquots of the sample within the well plate. The reader can further comprise one or more processors and one more memory units. The one or more processors can be programmed to determine the susceptibility of the bacteria to the antibiotic based on any changes in a solution characteristic of the aliquots within the test wells compared to the control well over time. In some embodiments, the conductive connectors can be leaf spring connectors. The leaf spring connectors can be made in part of a conductive metal or metal alloy. In some embodiments, each of the reader modules can further comprise a gasket disposed in between the PCBA and the sensor array lid covering the well plate placed on the plate tray. The gasket can be configured to create a partial seal around a top of the sensor array lid to control an evaporation rate of the aliquots of the sample and to control a humidity level and a partial pressure of oxygen within a test headspace above the well plate. In some embodiments, the gasket can be made in part of a semipermeable polymeric material having a Shore A hardness between about 20 to 55. In certain embodiments, the gasket can be made in part of a semipermeable polymeric material having a Shore A hardness of between about 45 to 50. The gasket can act as a perimeter surrounding the portions of the conductive connectors extending downward from the underside of the PCBA. In some embodiments, each of the reader m