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

Avails Medical Inc

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Publication Number

US-11385200-B2

Patent

Publication Date

2022-07-12

Expiration Date


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 method detects a susceptibility of one or more infectious agents to one or more anti-infectives by introducing a sample containing the infectious agents to a first filter and to a second filter. The first filter surface and the second filter surface are configured to capture the infectious agents, and the method uses filter capture followed by delivery to separate sensors. Two solution pathways are created by introducing different solutions to the first and second filter surfaces in fluid communication with the captured infectious agents.

A first solution is introduced to the first filter surface, where the first solution comprises a nutrient solution and one or more anti-infectives. A second solution is introduced to the second filter surface, where the second solution comprises the nutrient solution and does not comprise the one or more anti-infectives. Portions of the first and second solutions are separated from the respective filter surfaces and delivered to corresponding sensors, each sensor comprising a redox-active material.

The method monitors a first oxidation reduction potential (ORP) of the first solution and a second ORP of the portion of the second solution using one or more parameter analyzers coupled to the sensors. The ORP measurements are monitored in the absence of any added redox mediators or reporter molecules in both solutions. The method compares the first ORP with the second ORP to assess susceptibility of the infectious agents to the anti-infectives.

Claims Coverage

The independent claim is clm-00001. It contains 3 main inventive features: filter-split dual-solution delivery, mediator-free ORP sensing, and comparison of the ORPs to assess susceptibility. Dependent claims refine the anti-infective scope, redox-active materials, and the sample/infectious agent categories.

Filter capture with split first and second solutions

Introducing a sample comprising one or more infectious agents to a first filter and a second filter, capturing the infectious agents on the filter surfaces, and introducing to the first filter a first nutrient solution comprising one or more anti-infectives while introducing to the second filter a second nutrient solution that does not comprise the one or more anti-infectives.

Mediator-free redox sensing with corresponding redox sensors

Separating the first solution from the first filter surface and delivering a portion of the first solution to a first sensor comprising a redox-active material, separating the second solution from the second filter surface and delivering a portion of the second solution to a second sensor comprising the redox-active material or another redox-active material, and monitoring a first ORP and a second ORP using one or more parameter analyzers coupled to the sensors, where both ORPs are monitored in the absence of any added redox mediators or reporter molecules.

Comparing first ORP with second ORP to assess susceptibility

Comparing 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.

Anti-infectives from a specified set including combinations

Wherein the one or more anti-infectives include one or more of the listed antimicrobial agents or combinations.

Redox-active material selected from gold, platinum, metal oxide, and carbon layers

Wherein the redox-active material includes one or more layers selected from a gold layer, a platinum layer, a metal oxide layer, a carbon layer, or a combination thereof.

Metal oxide layer includes iridium oxide and/or ruthenium oxide

Wherein the metal oxide layer includes an iridium oxide layer, a ruthenium oxide layer, or both in combination.

Sample includes biological sample and/or bodily fluid and/or swab and/or derived culture

Wherein the sample includes one or more of a biological sample, bodily fluid, wound swab or sample, rectal swab or sample, and/or a bacterial culture derived from them.

Infectious agents include bacteria from one or more specified genera

Wherein the infectious agents include bacteria from one or more specified genera or combinations thereof.

The claim coverage centers on a split two-filter approach that delivers a nutrient-plus-anti-infective solution and a nutrient-only solution to separate redox-active sensors, then monitors ORP without added redox mediators or reporter molecules and compares the ORPs to assess susceptibility. Dependent claims refine which anti-infectives are included, possible redox-active material layers, and the types or categories of samples and bacterial genera.

Stated Advantages

The ORP is monitored without added redox mediators or reporter molecules.

Documented Applications

Detecting susceptibility of one or more infectious agents to one or more anti-infectives using ORP monitoring with a two-filter split and comparison of ORPs.

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