Since December 1974, when revised regulations concerning shipment of live virus vaccines issued by the Food and Drug Administration, Bureau of Biologics, went into effect, Merck Sharp & Dohme has transported all shipments of our vaccines and diluent syringes in containers with dry ice.
Previously, our live virus vaccines turned pink to red when reconstituted. This color is due to the addition of phenol red, which is a pH-sensitive indicator. Now, however, a few of
Self-calibrating, fluorescent nanoparticles with diameter far below 50 nm are synthesized with embedding a new ratiometric and pH sensitive indicator dye. The prompt response of the fluorophore allows for determining the intracellular pH.
We describe a material that allows for high spatial resolution pH mapping through tissue using X-ray excited luminescence chemical imaging (XELCI). This is especially useful for detecting implant associated infection and elucidating how the local biochemical environment changes during infection and treatment. To acquire one pixel in the image, a focused X-ray beam irradiates a small region of scintillators coated on the implant and the X-ray excited optical luminescence spectrum is modulated by indicator dyes to provide a chemically sensitive measurement with low background. Scanning the X-ray beam across the implant surface generates high spatial resolution chemical measurements. Two associated challenges are 1) to make robust sensors that can be implanted in tissue to measure local chemical concentrations and specifically for metal orthopedic implants, and 2) to conformally coat the implant surface with scintillators and pH indicator dyes in order to make measurements over a large area. Previously, we have physically pressed or glued a pH-sensitive hydrogel sensor to the surface of an implant, but this is impractical for imaging over large irregular device areas such as an orthopedic plate with holes and edges. Herein we describe a chemically sensitive and biocompatible XELI sensor material containing scintillator particles (Gd<sub>2</sub>O<sub>2</sub>S:Eu) and a pH sensitive hydrogel coating using a roughened epoxy coating. A two-part commercial grade epoxy film was tested and found to make the coating of pH sensitive layer adhere better to the titanium surface. Sugar and salt particles were added to the surface of the epoxy as it cured to create a roughened surface and increase surface area. On this roughened surface, a secondary layer of diacrylated polyethylene glycol (PEG) hydrogel, containing a pH sensitive dye, was polymerized. This layer was found to adhere well to the epoxy-coated implant unlike other previously tested polymer surfaces which delaminated when exposed to water or humidity. The focused X-ray beam enabled 0.5 mm spatial resolution through 1 cm thick tissue. The pH sensor coated orthopedic plate was imaged with XELCI through tissue with different pH to acquire a calibration curve. The plates were also imaged through tissue with low pH region from a Staphylococcus aureus biofilm grown on one section. These studies demonstrate the use of pH sensor coated orthopedic plates for mapping the surface pH through tissue during biofilm formation using XELCI.
We describe a material that allows for high spatial resolution pH mapping through tissue using X-ray excited luminescence chemical imaging (XELCI). This is especially useful for detecting implant associated infection and elucidating how the local biochemical environment changes during infection and treatment. To acquire one pixel in the image, a focused X-ray beam irradiates a small region of scintillators coated on the implant and the X-ray excited optical luminescence spectrum is modulated by indicator dyes to provide a chemically sensitive measurement with low background. Scanning the X-ray beam across the implant surface generates high spatial resolution chemical measurements. Two associated challenges are 1) to make robust sensors that can be implanted in tissue to measure local chemical concentrations and specifically for metal orthopedic implants, and 2) to conformally coat the implant surface with scintillators and pH indicator dyes in order to make measurements over a large area. Previously, we have physically pressed or glued a pH-sensitive hydrogel sensor to the surface of an implant, but this is impractical for imaging over large irregular device areas such as an orthopedic plate with holes and edges. Herein we describe a chemically sensitive and biocompatible XELI sensor material containing scintillator particles (Gd<sub>2</sub>O<sub>2</sub>S:Eu) and a pH sensitive hydrogel coating using a roughened epoxy coating. A two-part commercial grade epoxy film was tested and found to make the coating of pH sensitive layer adhere better to the titanium surface. Sugar and salt particles were added to the surface of the epoxy as it cured to create a roughened surface and increase surface area. On this roughened surface, a secondary layer of diacrylated polyethylene glycol (PEG) hydrogel, containing a pH sensitive dye, was polymerized. This layer was found to adhere well to the epoxy-coated implant unlike other previously tested polymer surfaces which delaminated when exposed to water or humidity. The focused X-ray beam enabled 0.5 mm spatial resolution through 1 cm thick tissue. The pH sensor coated orthopedic plate was imaged with XELCI through tissue with different pH to acquire a calibration curve. The plates were also imaged through tissue with low pH region from a Staphylococcus aureus biofilm grown on one section. These studies demonstrate the use of pH sensor coated orthopedic plates for mapping the surface pH through tissue during biofilm formation using XELCI.
Evaluation of Root pH Change Through Gel Containing pH-sensitive Indicator Bromocresol Purple