Direct and Continuous Monitoring of Multicomponent Antibiotic Gentamicin in Blood at Single-Molecule Resolution.

Area of Science:

• Biotechnology
• Nanotechnology
• Analytical Chemistry

Background:

• Point-of-care monitoring of small molecules in biofluids is critical for healthcare.
• Current detection methods face challenges due to low molecular recognition and complex biofluid matrices.
• Nanopore sensing shows promise for small molecule analysis but struggles with direct detection in complex samples.

Purpose of the Study:

• To develop a novel method for direct sensing of the small molecule drug gentamicin in whole blood.
• To utilize the Pseudomonas aeruginosa mechanosensitive channel of small conductance (PaMscS) nanopore for enhanced molecular detection.
• To establish a foundation for continuous, in vivo, single-molecule level drug monitoring.

Main Methods:

• Employing the PaMscS nanopore for direct detection of gentamicin in human whole blood.
• Leveraging the unique 'molecular sieve' structure of PaMscS for precise molecular discrimination.
• Developing a continuous monitoring device based on PaMscS for in vivo animal studies.

Main Results:

• PaMscS directly detected gentamicin in whole blood with high specificity, distinguishing components with minor structural differences.
• Gentamicin was measured in human whole blood within 10 minutes.
• Continuous in vivo monitoring of gentamicin in live rats was achieved for 2.5 hours without blood withdrawal, with in situ analysis of drug components.

Conclusions:

• The PaMscS nanopore sensor enables rapid, convenient, and highly sensitive drug monitoring at the single-molecule level.
• This technology significantly lowers the threshold for drug concentration monitoring, promoting optimized drug usage.
• The study establishes a robust platform for future development of continuous, in vivo, single-molecule resolution monitoring technologies.