Development of Luminescent pH Sensor Films for Monitoring Bacterial Growth Through Tissue

Abstract

Although implanted medical devices (IMDs) offer many benefits, they are susceptible to bacterial colonization and infections. Such infections are difficult to treat because bacteria could form biofilms on the implant surface, which reduce antibiotics penetration and generate local dormant regions with low pH and low oxygen. In addition, these infections are hard to detect early because biofilms are often localized on the surface. Herein, an optical sensor film is developed to detect local acidosis on an implanted surface. The film contains both upconverting particles (UCPs) that serve as a light source and a pH indicator that alters the luminescence spectrum. When irradiated with 980 nm light, the UCPs produce deeply penetrating red light emission, while generating negligible autofluorescence in the tissue. The basic form of the pH indicator absorbs more of upconversion luminescence at 661 nm than at 671 nm and consequently the spectral ratio indicates pH. Implanting this pH sensor film beneath 6-7 mm of porcine tissue does not substantially affect the calibration curve because the peaks are closely spaced. Furthermore, growth of Staphylococcus epidermidis on the sensor surface causes a local pH decrease that can be detected non-invasively through the tissue.

Nitric Oxide Releasing Materials Triggered by Near-Infrared Excitation Through Tissue Filters

“…Figure 3 illustrates the NO released as a function of the length of the photolysis time-interval indicated. This result is consistent with the earlier observation by Garcia et al 13 that 980 nm excitation of solutions containing both free RBS and erbium-based UCNPs generated significant quantities of NO. Free RBS alone in solution is insensitive to this excitation wavelength.…”

“…This behavior also contrasts to that for solutions of UNCPs and RBS 13 with a stationary laser beam, from which NO production was linear with time, although nonlinear with laser power as expected for a process where the upconversion involves sequential multiphoton absorptions. We attribute the behavior of the current systems to a "charging" effect, whereas the more often the oscillating laser beam addresses a particular nanoparticle repeatedly within a short time frame (the beam is moving at an average speed of ∼1 m s −1 ), the higher the probability that it will stimulate the upconversion, which requires the excitation of multiple Yb 3+ ion sensitizations.…”

“…An earlier study of RBS and UCNPs in solution 13 also showed that quantitative NO release has a nonlinear response to the intensity of the excitation source as does the upconverted visible emission. Thus, a much higher NO release could be expected for a higher intensity NIR beam, and this was accomplished by focusing to a diameter of ∼0.8 mm to give an intensity ∼40-fold greater than the expanded beam at the same total power.…”

“…This was surprising since solutions of RBS show no photochemistry under similar NIR excitation. 13 The NO detected from these E(0) PDs was quite small [∼7 pmoles (av) after 20 s irradiation] but was linearly proportional to the length of the photolysis interval. In addition, there was a noticeable decrease with each subsequent irradiation sequence.…”

“…The visible emissions from these UCNPs nicely overlap the broad absorption bands of RBS (Figure 2). 13 Three compositions of Na(Y/Gd)F 4 UCNPs (20% Gd, 20% Yb, and 2% Er), (20% Gd, 30% Yb, and 2% Er), and (20% Gd, 20% Yb, and 0.2% Tm), each coated with a thin shell of NaYF 4 to improve optical performance, 19 were used. These were prepared using a high throughput robotic system at the Molecular Foundry, 20 using procedures adapted from Ostrowski et al 21 with modest modifications.…”