Resistive pulse analysis of chiral amino acids utilizing metal-amino acid crystallization differences.

Here, we report a proof-of-concept resistive pulse method for analyzing chiral amino acids utilizing metal-amino acid crystallization differences. This method involves introducing an amino acid sample solution into a micropipette through a pressure-driven flow. The sample then mixes with a metal ion solution inside the pipette, forming metal-amino acid crystals. The crystal size depends on the enantiomeric excess (x) of chiral amino acid samples. Large x values lead to large crystals. The crystal size difference is then reflected in the resistive pulse size as they block the ionic transport in a micropipette to different extents. We used Cd-cystine crystallization as a model system and found approximately five times the mean current pulse size difference for racemic (x = 0) and L-only (x = +1) cystine samples. A similar result was observed for aspartate. Our discovery opens up new opportunities for micro/nanoscopic chiral amino acid analysis, which can potentially be used in single-cell analysis.

Nitric Oxide-Releasing Insert for Disinfecting the Hub Region of Tunnel Dialysis Catheters.

The use of tunneled dialysis catheters (TDCs) for patients in need of hemodialysis treatments (HDs) causes a significant number of bloodstream infections (BSIs), with very few viable preventative/treatment methods. Use of antibiotics is relatively ineffective due to the development of multidrug-resistant bacterial strains and the inability to penetrate bacterial biofilms. Nitric oxide (NO) is an endogenous gas molecule that has broad-spectrum antimicrobial/antibiofilm activity. In this study, the potential of creating a NO-releasing insert device that is attached onto the hub region cap of TDCs and locally releases NO within the TDC hub is evaluated for its antimicrobial/antibiofilm effectiveness. The NO-releasing insert contains the natural NO donor S-nitrosoglutathione (GSNO), along with zinc oxide (ZnO) nanoparticles to accelerate NO release from the GSNO, within a short silicone tube that is sealed at both ends and attached to the catheter cap. An in vitro 3-d-long antimicrobial study using catheter hubs yielded >6.6 log reductions of both Pseudomonas aeruginosa and Staphylococcus aureus for the NO-releasing insert device compared to controls. Two 14-d-long sheep studies demonstrated that the NO-releasing insert devices are exceptionally potent at preventing bacteria/biofilm growth on the inner lumen walls of TDCs compared to controls that have no preventative treatment devices as well as implanted TDCs that have commercially available chlorhexidine-treated insert devices placed within the hub regions.

Feedback-controlled photolytic gas phase nitric oxide delivery from S-nitrosothiol-doped silicone rubber films.

Constant therapeutic gas phase nitric oxide (NO) delivery is achieved from S-nitrosothiol (RSNO) type NO donor doped silicone rubber films using feedback-controlled photolysis. For photo-release of the NO gas, the intensity of the LED light source is controlled via a PID (proportional-integral-derivative) controller implemented on a microcontroller. The NO concentration within the emitted gas phase is monitored continuously with a commercial amperometric NO gas sensor. NO release was accurately adjustable up to 10 ppm across a broad range of setpoints with response times of roughly 1 min or less. When NO is generated into an air recipient stream, lower NO yields and a comparable level of toxic nitrogen dioxide (NO2) formation is observed. However, NO gas generated into an N2 recipient gas stream can be blended into pure O2 with very low NO2 formation. Following scale-up, this technology could be used for point-of-care gas phase NO generation as an alternative for currently used gas cylinder technology for treatment of health conditions where inhaled NO is beneficial, such as pulmonary hypertension, hypoxemia, and cystic fibrosis.

Controlled light-induced gas phase nitric oxide release from S-nitrosothiol-doped silicone rubber films.

The light induced nitric oxide (NO) release properties of S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO) NO donors doped within polydimethylsiloxane (PDMS) films (PDMS-SNAP and PDMS-GSNO respectively) for potential inhaled NO (iNO) applications is examined. To achieve photolytic release of gas phase NO from the PDMS-SNAP and PDMS-GSNO films, narrow-band LED light sources are employed and the NO concentration in a N2 sweep gas above the film is monitored with an electrochemical NO sensor. The NO release kinetics using LED sources with different nominal wavelengths and optical power densities are reported. The effect of the NO donor loading within the PDMS films is also examined. The NO release levels can be controlled by the LED triggered release from the NO donor-doped silicone rubber films in order to generate therapeutic levels in a sweep gas for suitable durations potentially useful for iNO therapy. Hence this work may lay the groundwork for future development of a highly portable iNO system for treatment of patients with pulmonary hypertension, hypoxemia, and cystic fibrosis.