Implanted medical device-associated infections are a leading cause of fixation failure, and early diagnosis is the key to successful treatment. During infection, acidosis near the implant plays a role in antibiotic resistance and low pH is a potential infection indicator. Herein, we describe a pH sensor which attaches to the implants to noninvasively image local pH with high spatial resolution. The sensor has two layers: a scintillator layer which emits 620 and 700 nm light upon X-ray irradiation and a pH indicator layer containing bromocresol green dye that absorbs 620 nm luminescence in neutral/basic pH and passes 700 nm light at all pHs. We also developed a dedicated imaging system capable of scanning relatively large specimens through thick tissues. A focused X-ray beam irradiates one spot on the sensor, and the 620 to 700 nm peak ratio is measured to determine the local pH; images are acquired by scanning the X-ray beam across the surface and measuring the pH point-by-point. The sensor was covered with varying thickness slices of chicken breast tissue (0−19 mm) to evaluate how the tissue affects the peak intensity and ratio. Thick tissues attenuated both 620 and 700 nm light, with more attenuation at 620 nm than 700 nm. Although this spectral distortion shifted the pH calibration curve, the effect could be corrected for using a scintillator film region with no pH indicator layer as a spectral reference. The sensor was attached to an orthopedic plate affixed to a human cadaveric tibia and imaged through tissue. This approach provides both high spatial resolution from focused X-ray excitation and surface chemical specificity from the indicator dye, providing a tool for imaging local pH through tissue.

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 2 O 2 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.

X-ray excited luminescent chemical imaging (XELCI) uses a combination of X-ray excitation to provide high resolution and optical detection to provide chemical sensing. A key application is to detect and study implant-associated infection. The implant is coated with a layer of X-ray scintillators which generate visible near infrared light when irradiated with an X-ray beam. This light first passes through a pH indicator dye-loaded film placed over the scintillator film in order to modulate the luminescence spectrum according to pH. The light then passes through tissue is collected and the spectral ratio measured to determine pH. A focused X-ray beam irradiates a point in the scintillator film, and a pH image is formed point-by-point by scanning the beam across the sample. The sensor and scanning system are described along with preliminary results showing images in rabbit models.

<p>Using ultrasound luminescent chemical imaging (ULCI) technique we<i> </i>imaged changes in the luminescence spectra of the ultrasound luminescent film modulated by a pH sensitive dye coating in different pH environments through a light scattering media. Our results show that high resolution images can be obtained through scattering media, and that the ultrasound luminescent film could be modulated by the pH sensitive dye.</p>

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 (Gd₂O₂S: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.

No abstract

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 (Gd₂O₂S: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 (Gd₂O₂S: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.