Inductively coupled capacitor wireless sensor system for rapid antimicrobial susceptibility testing

Inventors

Ren, DachengXu, Yikang

Assignees

Syracuse University

Publication Number

US-12071602-B2

Publication Date

2024-08-27

Expiration Date

2042-10-25

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Abstract

An electrochemical biosensor based on magnetically coupled LC sensors for the rapid detection of microbial growth and sensitivity to microbials. The engineered LC sensors can be placed in 96 well plates and communicate the reading remotely with a receiver coil for signal analysis. The sensors were validated by testing the growth of Escherichia. coli, Staphylococcus. aureus, and Pseudomonas aeruginosa in the presence and absence of different antibiotics. Drug-resistant strains were used as controls. Bacterial growth was detected within 30 mins of culture inoculation, allowing rapid determination of antibiotic susceptibility at the phenotypic level. The pattern shown in the LC sensor AST is consistent with results collected with traditional optical density (OD) 600 nm measurement, additional validation was also performed with lysogeny broth (LB) dosed with fetal bovine serum (FBS). With the compatibility with 96-well plates, this rapid AST may be used for low-cost, point-of-care applications.

Core Innovation

The present invention provides a rapid phenotypic antimicrobial susceptibility testing (AST) system utilizing a wirelessly magnetically coupled LC sensor that exploits the capacitive properties of bacteria. Unlike conventional approaches that require targeted sample enrichment or surface modifications, this system enables direct monitoring of bacterial growth and killing/inhibition in response to antibiotics, facilitating rapid diagnosis of bacterial infections and antimicrobial susceptibility in a simple format. Bacterial cultures, with or without antibiotics, are aliquoted into wells containing the sensor; the resonance frequency between the sensor and an external receiver coil is periodically measured wirelessly, and the permittivity of the bacterial culture calculated based on this data.

The core problem addressed by this invention is the delayed and complicated nature of current antimicrobial susceptibility testing methods, which often require extensive time (1–2 days for traditional phenotypic methods), detailed knowledge of resistance genes (for genotypic ASTs), or involve complex equipment and sample preparation unsuitable for rapid, point-of-care clinical use. Existing methods are insufficient for timely detection, potentially missing the critical window for effective patient treatment. The invention specifically aims to enable rapid, high-throughput, low-cost phenotypic detection of antimicrobial resistance that can produce results within 30 minutes, without requiring complex processing or specialized consumables.

The system comprises a well plate (such as a standard 96-well plate) where each well contains a sensor designed and optimized for high sensitivity through parameters like coil turns, diameter, and gap dimensions. A receiver coil placed below the well plate communicates wirelessly with each sensor, while an impedance analyzer determines the resonance frequency and computes permittivity changes induced by bacterial growth or inhibition. The results are plotted as time series of permittivity, where the slope of the curve during the initial measurement period (e.g., 30 minutes) provides a sensitivity score, allowing rapid determination of antibiotic susceptibility. The system is compatible with automation, standard labware, and minimal sample preparation.

Claims Coverage

There are two independent claims in the patent, each introducing an inventive feature: a system for rapid antimicrobial susceptibility testing and a method for performing an antimicrobial susceptibility test.

System for rapid antimicrobial susceptibility testing using wirelessly coupled LC sensors and impedance analysis

The inventive feature consists of: - A well including a cavity designed to receive a sample containing a microbial population and an antimicrobial. - A sensor, having a set of defined parameters, positioned vertically within the well to ensure contact with the sample. - A receiver located under the well, wirelessly coupled to the sensor. - An impedance analyzer connected to the receiver, configured to: - Identify the resonance frequency between the sensor and the receiver. - Record resonance frequency data over a predetermined set of time intervals. - Calculate the permittivity of the sample based on the resonance frequency and the defined parameters of the sensor. - Track the permittivity over a second predetermined time period.

Method for performing an antimicrobial susceptibility test by tracking permittivity over time

The inventive feature comprises the following steps: 1. Providing a well with a cavity, a sensor with defined parameters in the well, and a receiver under the well wirelessly coupled to the sensor. 2. Adding a sample containing a microbial population and an antimicrobial so that it contacts the sensor. 3. Using an impedance analyzer connected to the receiver to identify the resonance frequency between the sensor and receiver. 4. Recording the resonance frequency over a predetermined set of time intervals. 5. Calculating the permittivity of the sample based on the resonance frequency and sensor parameters. 6. Tracking the calculated permittivity over a second predetermined time period.

In summary, the patent claims cover both a system and a method for rapid antimicrobial susceptibility testing. The system uses wirelessly coupled LC sensors and impedance analysis to track changes in permittivity caused by microbial growth or inhibition, while the method outlines the steps necessary to conduct such tests using the system. Both inventive features enable rapid, contactless, and high-throughput determination of microbial susceptibility.

Stated Advantages

Provides rapid detection of antimicrobial susceptibility at the phenotypic level within approximately 30 minutes.

Bypasses the need for surface modifications, sample enrichment, or complex preparation, enabling simpler and more accessible testing.

Compatible with standard 96-well plates and automated workflow systems for high-throughput, low-cost applications.

Eliminates the requirement for advanced data analysis or handling of large data sets.

Does not require specific cartridges or consumables for particular strains, allowing broader applicability.

Possible use with clinical samples after simple dilution, as demonstrated with serum-spiked media.

Documented Applications

Rapid antimicrobial susceptibility testing (AST) of bacterial cultures to determine susceptibility to various antibiotics.

High-throughput, low-cost phenotypic detection and monitoring of microbial growth or inhibition in clinical microbiology laboratories.

Point-of-care diagnostic testing for bacterial infections using standard lab equipment and automated workflows.

Testing of clinical samples, including those spiked with fetal bovine serum to mimic human serum, for feasibility in clinical settings.

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