Apparatus, systems, and methods for determining susceptibility of microorganisms to anti-infectives
Inventors
KNOPFMACHER, Oren S. • Herget, Meike • Estabrook, August • RAJAN, Nitin K. • Laufer, Michael D.
Assignees
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Abstract
Various devices, systems and methods of detecting a susceptibility of one or more infectious agents to one or more anti-infectives are described herein. In one embodiment, a method of detecting the susceptibility of the infectious agents to the anti-infectives involves introducing a sample comprising the infectious agents to a filter comprising a filter surface. The filter surface can be configured to capture the infectious agents in the sample. The method can also involve introducing a solution to the filter surface such that the solution is in fluid communication with the infectious agents captured on the filter surface. The solution can comprise nutrients and one or more anti-infectives. The method can further involve monitoring an oxidation reduction potential (ORP) of the solution using one or more parameter analyzers coupled to a sensor currently in fluid communication with the solution to assess the susceptibility of the infectious agents to the anti-infectives.
Core Innovation
The disclosed invention provides a system for detecting a susceptibility of one or more infectious agents to one or more anti-infectives. The system includes a first housing with a first surface and a second housing with a second surface, where each housing is configured to receive an aliquot of a sample comprising one or more infectious agents. The first fluid delivery conduit introduces a first solution to the first surface in fluid communication with the infectious agents, and the first solution comprises a nutrient solution and one or more anti-infectives.
The second fluid delivery conduit introduces a second solution to the second surface such that the second solution is in fluid communication with the infectious agents on the second surface. The second solution comprises the nutrient solution and does not comprise the one or more anti-infectives. The system includes a first sensor with a redox-active layer positioned on top of at least one conductive metallic layer, coupled to the first housing to receive a portion of the first solution, and a second sensor with a redox-active layer positioned on top of at least one conductive metallic layer, coupled to the second housing to receive a portion of the second solution.
One or more parameter analyzers are coupled to the first sensor and the second sensor, and are configured to monitor a first oxidation reduction potential (ORP) of the first solution and to monitor a second ORP of the second solution. The first ORP is monitored in the absence of any added redox mediators or reporter molecules in the first solution, and the second ORP is monitored in the absence of any added redox mediators or reporter molecules in the second solution. The parameter analyzers compare the first ORP with the second ORP to assess the susceptibility of the infectious agents to the anti-infectives.
Claims Coverage
The independent claim defines a susceptibility-detection system that monitors and compares ORP from two separate solution conditions. The claim set includes 10 dependent members that refine the selectable anti-infectives, sensor redox-active layer materials, sensor electrode configuration, and sample or infectious-agent scope.
Susceptibility detection using dual-housing solution comparison
A system with a first housing and a second housing, each receiving an aliquot of a sample containing one or more infectious agents, and fluid delivery of two different solutions, nutrient plus anti-infectives versus nutrient without anti-infectives, in fluid communication with the infectious agents.
Redox-active ORP sensors without added mediators or reporter molecules
A first sensor and a second sensor, each comprising a redox-active layer positioned on top of at least one conductive metallic layer, coupled to respective housings to receive portions of the first and second solutions, with ORP monitored in the absence of any added redox mediators or reporter molecules.
Comparative ORP monitoring to assess susceptibility
One or more parameter analyzers configured to monitor a first ORP and a second ORP and to compare the first ORP with the second ORP to assess the susceptibility of the one or more infectious agents to the one or more anti-infectives.
Defined anti-infectives and antifungals for testing
The one or more anti-infectives are selected from specified antimicrobial drug classes and agents, and/or combinations thereof, including antifungals such as Amphotericin B, Flucytosine, Fluconazole, Ketoconazole, Itraconazole, Posaconazole, Ravuconazole, and Voriconazole.
Redox-active layer material set
The redox-active layer includes gold, platinum, a metal oxide, carbon, or combinations of these materials.
Active electrode and reference electrode configuration
The first sensor includes an active electrode and a reference electrode.
Sample and sample-source inputs
The sample can be a biological sample, bodily fluid, wound swab or sample, rectal swab or sample, a bacterial culture derived from them, or combinations thereof.
Infectious-agent bacterial genera scope
The one or more infectious agents are bacteria from a specified list of bacterial genera or combinations thereof.
Across the claim set, susceptibility is assessed by comparing ORP measured by a pair of sensors fed from two solution conditions, nutrient with anti-infectives versus nutrient without anti-infectives. The dependent claims further specify allowable anti-infectives, sensor redox-active layer materials, electrode configuration, and the types of samples and bacterial genera covered.
Stated Advantages
Provides a susceptibility assessment of infectious agents to anti-infectives by comparing first ORP and second ORP.
Documented Applications
Detecting the susceptibility of one or more infectious agents to one or more anti-infectives using a nutrient solution condition with anti-infectives and a nutrient solution condition without anti-infectives.
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