Autonomic Innervation and Segmental Muscular Disconnections at the Human Pulmonary Vein-Atrial Junction Implications for Catheter Ablation of Atrial-Pulmonary Vein Junction

ObjectivesThis study sought to examine the muscle connections and autonomic nerve distributions at the human pulmonary vein (PV)-left atrium (LA) junction.BackgroundOne approach to catheter ablation of atrial fibrillation (AF) is to isolate PV muscle sleeves from the LA. Elimination of vagal response further improves success rates.MethodsWe performed immunohistochemical staining on 192 circumferential venoatrial segments (32 veins) harvested from 8 autopsied human hearts using antibodies to tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT).ResultsMuscular discontinuities of widths 0.1 to 5.5 mm (1.1 ± 1.0 mm) and abrupt 90° changes in fiber orientation were found in 70 of 192 (36%) and 36 of 192 (19%) of PV-LA junctions, respectively. Although these anisotropic features were more common in the anterosuperior junction (p < 0.01), they were also present around the entire PV-LA junction. Autonomic nerve density was highest in the anterosuperior segments of both superior veins (p < 0.05 versus posteroinferior) and inferior segments of both inferior veins (p < 0.05 vs. superior), highest in the LA within 5 mm of the PV-LA junction (p < 0.01), and higher in the epicardium than endocardium (p < 0.01). Adrenergic and cholinergic nerves were highly co-located at tissue and cellular levels. A significant proportion (30%) of ganglion cells expressed dual adrenocholinergic phenotypes.ConclusionsMuscular discontinuities and abrupt fiber orientation changes are present in >50% of PV-LA segments, creating significant substrates for re-entry. Adrenergic and cholinergic nerves have highest densities within 5 mm of the PV-LA junction, but are highly co-located, indicating that it is impossible to selectively target either vagal or sympathetic nerves during ablation procedures

Fluorescence-suppressed time-resolved Raman spectroscopy of pharmaceuticals using complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) detector

In this work, we utilize a short-wavelength, 532-nm picosecond pulsed laser coupled with a time-gated complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) detector to acquire Raman spectra of several drugs of interest. With this approach, we are able to reveal previously unseen Raman features and suppress the fluorescence background of these drugs. Compared to traditional Raman setups, the present time-resolved technique has two major improvements. First, it is possible to overcome the strong fluorescence background that usually interferes with the much weaker Raman spectra. Second, using the high photon energy excitation light source, we are able to generate a stronger Raman signal compared to traditional instruments. In addition, observations in the time domain can be performed, thus enabling new capabilities in the field of Raman and fluorescence spectroscopy. With this system, we demonstrate for the first time the possibility of recording fluorescence-suppressed Raman spectra of solid, amorphous and crystalline, and non-photoluminescent and photoluminescent drugs such as caffeine, ranitidine hydrochloride, and indomethacin (amorphous and crystalline forms). The raw data acquired by utilizing only the picosecond pulsed laser and a CMOS SPAD detector could be used for identifying the compounds directly without any data processing. Moreover, to validate the accuracy of this time-resolved technique, we present density functional theory (DFT) calculations for a widely used gastric acid inhibitor, ranitidine hydrochloride. The obtained time-resolved Raman peaks were identified based on the calculations and existing literature. Raman spectra using non-time-resolved setups with continuous-wave 785- and 532-nm excitation lasers were used as reference data. Overall, this demonstration of time-resolved Raman and fluorescence measurements with a CMOS SPAD detector shows promise in diverse areas, including fundamental chemical research, the pharmaceutical setting, process analytical technology (PAT), and the life sciences.Peer reviewe

An Adaptable, Portable Microarray Reader for Biodetection

We have developed an inexpensive portable microarray reader that can be applied to standard microscope slide-based arrays and other array formats printed on chemically modified surfaces. Measuring only 19 cm in length, the imaging device is portable and may be applicable to both triage and clinical settings. For multiplexing and adaptability purposes, it can be modified to work with multiple excitation/emission wavelengths. Our device is shown to be comparable to a commercial laser scanner when detecting both streptavidin-biotin and antibody interactions. This paper presents the development and characterization of a handheld microarray imager and directly compares it with a commercial scanner

Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer

The overall prognosis of bladder cancer has not been improved over the last 30 years and therefore, there is a great medical need to develop novel diagnosis and therapy approaches for bladder cancer. We developed a multifunctional nanoporphyrin platform that was coated with a bladder cancer-specific ligand named PLZ4. PLZ4-nanoporphyrin (PNP) integrates photodynamic diagnosis, image-guided photodynamic therapy, photothermal therapy and targeted chemotherapy in a single procedure. PNPs are spherical, relatively small (around 23&nbsp;nm), and have the ability to preferably emit fluorescence/heat/reactive oxygen species upon illumination with near infrared light. Doxorubicin (DOX) loaded PNPs possess slower drug release and dramatically longer systemic circulation time compared to free DOX. The fluorescence signal of PNPs efficiently and selectively increased in bladder cancer cells but not normal urothelial cells in&nbsp;vitro and in an orthotopic patient derived bladder cancer xenograft (PDX) models, indicating their great potential for photodynamic diagnosis. Photodynamic therapy with PNPs was significantly more potent than 5-aminolevulinic acid, and eliminated orthotopic PDX bladder cancers after intravesical treatment. Image-guided photodynamic and photothermal therapies synergized with targeted chemotherapy of DOX and significantly prolonged overall survival of mice carrying PDXs. In conclusion, this uniquely engineered targeting PNP selectively targeted tumor cells for photodynamic diagnosis, and served as effective triple-modality (photodynamic/photothermal/chemo) therapeutic agents against bladder cancers. This platform can be easily adapted to individualized medicine in a clinical setting and has tremendous potential to improve the management of bladder cancer in the clinic

Progress and Challenges of Point-of-Need Photonic Biosensors for the Diagnosis of COVID-19 Infections and Immunity

The new coronavirus disease, COVID-19, caused by SARS-CoV-2, continues to affect the world and after more than two years of the pandemic, approximately half a billion people are reported to have been infected. Due to its high contagiousness, our life has changed dramatically, with consequences that remain to be seen. To prevent the transmission of the virus, it is crucial to diagnose COVID-19 accurately, such that the infected cases can be rapidly identified and managed. Currently, the gold standard of testing is polymerase chain reaction (PCR), which provides the highest accuracy. However, the reliance on centralized rapid testing modalities throughout the COVID-19 pandemic has made access to timely diagnosis inconsistent and inefficient. Recent advancements in photonic biosensors with respect to cost-effectiveness, analytical performance, and portability have shown the potential for such platforms to enable the delivery of preventative and diagnostic care beyond clinics and into point-of-need (PON) settings. Herein, we review photonic technologies that have become commercially relevant throughout the COVID-19 pandemic, as well as emerging research in the field of photonic biosensors, shedding light on prospective technologies for responding to future health outbreaks. Therefore, in this article, we provide a review of recent progress and challenges of photonic biosensors that are developed for the testing of COVID-19, consisting of their working fundamentals and implementation for COVID-19 testing in practice with emphasis on the challenges that are faced in different development stages towards commercialization. In addition, we also present the characteristics of a biosensor both from technical and clinical perspectives. We present an estimate of the impact of testing on disease burden (in terms of Disability-Adjusted Life Years (DALYs), Quality Adjusted Life Years (QALYs), and Quality-Adjusted Life Days (QALDs)) and how improvements in cost can lower the economic impact and lead to reduced or averted DALYs. While COVID19 is the main focus of these technologies, similar concepts and approaches can be used and developed for future outbreaks of other infectious diseases

Microfluidics on lensless, semiconductor optical image sensors: challenges and opportunities for democratization of biosensing at the micro-and nano-scale

Optical image sensors are 2D arrays of pixels that integrate semiconductor photodiodes and field effect transistors for efficient photon conversion and processing of generated electrons. With technological advancements and subsequent democratization of these sensors, opportunities for integration with microfluidics devices are currently explored. 2D pixel arrays of such optical image sensors can reach dimensions larger than one centimeter with a sub-micrometer pixel size, for high spatial resolution lensless imaging with large field of view, a feat that cannot be achieved with lens-based optical microscopy. Moreover, with advancements in fabrication processes, the field of microfluidics has evolved to develop microfluidic devices with an overall size below one centimeter and individual components of sub-micrometer size, such that they can now be implemented onto optical image sensors. The convergence of these fields is discussed in this article, where we review fundamental principles, opportunities, challenges, and outlook for integration, with focus on contact-mode imaging configuration. Most recent developments and applications of microfluidic lensless contact-based imaging to the field of biosensors, in particular those related to the potential for point of need applications, are also discussed

Nanometer-scale sizing accuracy of particle suspensions on an unmodified cell phone using elastic light scattering.

We report on the construction of a Fourier plane imaging system attached to a cell phone. By illuminating particle suspensions with a collimated beam from an inexpensive diode laser, angularly resolved scattering patterns are imaged by the phone's camera. Analyzing these patterns with Mie theory results in predictions of size distributions of the particles in suspension. Despite using consumer grade electronics, we extracted size distributions of sphere suspensions with better than 20 nm accuracy in determining the mean size. We also show results from milk, yeast, and blood cells. Performing these measurements on a portable device presents opportunities for field-testing of food quality, process monitoring, and medical diagnosis

Hydrophobicity-driven self-assembly of protein and silver nanoparticles for protein detection using surface-enhanced Raman scattering

Kahraman M, Balz BN, Wachsmann-Hogiu S. Hydrophobicity-driven self-assembly of protein and silver nanoparticles for protein detection using surface-enhanced Raman scattering. The Analyst. 2013;138(10):2906-2913.Surface-enhanced Raman scattering (SERS) is a promising analytical technique for the detection and characterization of biological molecules and structures. The role of hydrophobic and hydrophilic surfaces in the self-assembly of protein-metallic nanoparticle structures for label-free protein detection is demonstrated. Aggregation is driven by both the hydrophobicity of the surface as well as the charge of the proteins. The best conditions for obtaining a reproducible SERS signal that allows for sensitive, label-free protein detection are provided by the use of hydrophobic surfaces and 16 x 10(11) NPs per mL. A detection limit of approximately 0.5 mu g mL(-1) is achieved regardless of the proteins' charge properties and size. The developed method is simple and can be used for reproducible and sensitive detection and characterization of a wide variety of biological molecules and various structures with different sizes and charge status