Surface-Enhanced Spatially Offset Raman Spectroscopy in Tissue.

One aim of personalized medicine is to use continuous or on-demand monitoring of metabolites to adjust prescription dosages in real time. Surface-enhanced spatially offset Raman spectroscopy (SESORS) is an optical technique capable of detecting surface-enhanced Raman spectroscopy (SERS)-active targets under a barrier, which may enable frequent metabolite monitoring. Here we investigate how the intensity of the signal from SERS-active material varies spatially through tissue, both experimentally and in a computational model. Implant-sized, SERS-active hydrogel was placed under different thicknesses of contiguous tissue. Emission spectra were collected at the air-tissue boundary over a range of offsets from the excitation site. New features were added to the Monte Carlo light-tissue interaction model to modify the optical properties after inelastic scattering and to calculate the distribution of photons as they exit the model. The Raman signals were detectable through all barrier thicknesses, with strongest emission for the case of 0 mm offset between the excitation and detector. A steep decline in the signal intensities occurred for offsets greater than 2 mm. These results did not match published SORS work (where targets were much larger than an implant). However, the model and experimental results agree in showing the greatest intensities at 0 mm offset and a steep gradient in the intensities with increasing offset. Also, the model showed an increase in the number of photons when the new, longer wavelengths were used following the Stokes shift for scattering and the graphical display of the exiting photons was helpful in the determination and confirmation of the optimal offset.

Comparison of SERS pH probe responses after microencapsulation within hydrogel matrices.

SIGNIFICANCE: Personalized medicine requires the tracking of an individual's metabolite levels over time to detect anomalies and evaluate the body's response to medications. Implanted sensors offer effective means to continuously monitor specific metabolite levels, provided they are accurate, stable over long time periods, and do no harm. AIM: Four types of hydrogel embedded with pH-sensitive sensors were evaluated for their accuracy, sensitivity, reversibility, longevity, dynamic response, and consistency in static versus dynamic conditions and long-term storage. APPROACH: Raman spectroscopy was first used to calibrate the intensity of pH-sensitive peaks of the Raman-active hydrogel sensors in a static pH environment. The dynamic response was then assessed for hydrogels exposed to changing pH conditions within a flow cell. Finally, the static pH response after 5 months of storage was determined. RESULTS: All four types of hydrogels allowed the surface-enhanced Raman spectroscopy (SERS) sensors to respond to the pH level of the local environment without introducing interfering signals, resulting in consistent calibration curves. When the pH level changed, the probes in the gels were slow to reach steady-state, requiring several hours, and response times were found to vary among hydrogels. Only one type, poly(2-hydroxyethyl methacrylate) (pHEMA), lasted five months without significant degradation of dynamic range. CONCLUSIONS: While all hydrogels appear to be viable candidates as biocompatible hosts for the SERS sensing chemistry, pHEMA was found to be most functionally stable over the long interval tested. Poly(ethylene glycol) hydrogels exhibit the most rapid response to changing pH. Since these two gel types are covalently cross-linked and do not generally degrade, they both offer advantages over sodium alginate for use as implants.

Enzyme-coated Janus nanoparticles that selectively bind cell receptors as a function of the concentration of glucose.

A method is proposed for controlling the number of nanoparticles bound to cell membranes via RGDS peptide-integrin interactions. It consists of propelling nanoparticles bearing the peptides with enzymes (glucose oxidase), which disrupts biomolecular interactions as a function of the concentration of enzyme substrate (glucose).

Light-Triggered Inactivation of Enzymes with Photothermal Nanoheaters.

A universal method for inactivating enzymes on demand is introduced, which involves irradiating nanorod-bound enzymes with near-infrared light. The subsequent generation of plasmonic heat denatures the enzymes selectively without damaging other proteins or cell membranes present in the same solution.

Naked-eye detection as a universal approach to lower the limit of detection of enzyme-linked immunoassays.

Colorimetric biosensors for the detection of analytes with the naked eye are required in environmental monitoring, point-of-care diagnostics, and analyses in resources constrained settings, where detection instruments may not be available. However, instrument-based detection methods are usually more adequate for detecting small variations in the signal compared to naked-eye detection schemes, and consequently the limit of detection of the latter is usually higher than the former. Here, we demonstrate that the limit of detection of colorimetric enzyme-linked immunoassays can be decreased several orders of magnitude when using naked-eye detection instead of a spectrophotometer for detecting the signal. The key step to lower the limit of detection is adding a small volume of chromogenic substrate during the signal generation step. This generates highly colored solutions that can be easily visualized with the naked eye and recorded with the camera of a mobile phone. The proposed method does not require expensive equipment or complex protocols to enhance the signal, and therefore it is a universal approach to lower the limit of detection of colorimetric enzyme-linked immunoassays.

Laparoscopic nephrectomy for adult polycystic kidney disease: safety, feasibility, and early outcomes.

BACKGROUND AND PURPOSE: Indications for laparoscopic renal surgery are increasing; however, benefits in adult polycystic kidney disease (APKD) remain uncertain. Our objective was to systematically synthesize the reported literature on safety, feasibility, complications, and early outcomes of laparoscopic nephrectomy in APKD to determine clinical benefits for surgical practice. METHODS: We conducted a meta-analysis of the published literature reporting on laparoscopic nephrectomy in APKD between 1991 and 2013. The criteria from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) study were used to assess the quality of reported literature. RESULTS: One prospective and 15 retrospective studies of low to modest quality (according to the STROBE checklist) were identified, reporting on 293 patients who underwent laparoscopic nephrectomy for APKD. None of the studies was a randomized clinical trial (RCT). The transperitoneal approach was the most commonly used technique. Body mass index ranged from 16 to 57 (mean 26.2 kg/m(2); 53% of patients were dialysis dependent, and 31% had a previous or simultaneous transplant. Kidney length ranged from 8 to 50 cm (mean 34.5cm), and the mean mass of affected kidneys was 1647 g (range 132 g-7200 g). Duration of hospital stay ranged from 2.6 to 11 days (mean 4.9 days). Operative time ranged from 90 to 568 minutes, with 16.2% of patients needing blood transfusion. There were 24 intraoperative complications and 68 postoperative complications, a rate of 8% and 24%, respectively. A total of 16 (5%) cases were converted to an open technique. No mortality was reported in any of the included studies. CONCLUSION: The quality of the included studies is poor, and it is difficult to argue for or against change in clinical practice because the evidence included is of level 3 and 4 only. Higher quality studies are needed to demonstrate that the technique is generalizable across all populations.