Apparatus, systems, and methods for determining the susceptibility of infectious agents to anti-infectives

Inventors

KNOPFMACHER, Oren S. • Herget, Meike • RAJAN, Nitin K. • WAHBA, Ashraf M.

Assignees

Avails Medical Inc

Abstract

Various methods, devices, and systems for determining the susceptibility of infectious agents to anti-infectives are disclosed herein. A method comprises introducing an inoculum solution comprising the infectious agent into a sample receiving space of a diagnostic device. The sample receiving space comprises a plurality of growth control wells devoid of the anti-infective and a plurality of active electrode wells comprising the anti-infective at differing concentrations. A water immiscible liquid can be introduced into the sample receiving space to seal the plurality of wells and the diagnostic device can be incubated for a period of time. The minimum inhibitory concentration (MIC) of the anti-infective on the infectious agent can be determined by monitoring and comparing one or more solution characteristics of the inoculum solution within the active electrode wells with the one or more solution characteristics of the inoculum solution with the growth control wells.

Core Innovation

The invention relates to determining a susceptibility of an infectious agent to an anti-infective by determining a minimum inhibitory concentration (MIC) using a diagnostic device. The diagnostic device includes a sample receiving space with a plurality of wells that include pH electrode wells and oxidation reduction potential (ORP) electrode wells, and at least one of these wells is a growth control well devoid of the anti-infective. At least two of the pH electrode wells and at least two of the ORP electrode wells are active electrode wells that include the anti-infective at differing concentrations.

In the disclosed method, an inoculum solution comprising the infectious agent is introduced into the sample receiving space through a sample inlet port. A reference buffer is introduced into a buffer receiving space through a buffer inlet port, where the buffer receiving space includes a plurality of reference electrode wells with reference electrodes that are in fluid communication with the pH electrode wells and the ORP electrode wells. After the inoculum solution fills the wells, a water immiscible liquid is introduced into the sample receiving space through the sample inlet port.

The device is incubated for a predetermined time period, and one or more solution characteristics of the inoculum solution within the active electrode wells and the growth control wells are monitored during incubation. The MIC is determined by comparing the solution characteristics in the growth control wells with the solution characteristics in the active electrode wells, optionally using growth-curve attributes derived from the monitored characteristics. The described solution characteristics include pH and/or oxidation reduction potential (ORP), monitored using pH electrodes and ORP electrodes.

Claims Coverage

Four independent claims are identified. Together, they define a susceptibility/MIC determination approach using multi-well diagnostic devices with pH and ORP electrodes, growth control and active electrode wells with differing anti-infective concentrations, reference buffer addition in fluid communication with the electrodes, water immiscible liquid introduction, incubation, monitoring of solution characteristics over time, and comparison to determine MIC.

Across the four independent claims, the core inventive contribution is a susceptibility testing workflow in which inoculum is introduced into a multi-well diagnostic device having growth control wells devoid of the anti-infective and active wells containing the anti-infective at differing concentrations, solution characteristics are monitored over time, a reference buffer and water immiscible liquid are introduced as specified, and a computing comparison between control and active wells is used to determine MIC.

Stated Advantages

Documented Applications