Biology subjects

Wang, B.-Y.

Publications and source records attributed to Wang, B.-Y..

5 recordsLinked to original sources

bioRxiv2024

Diversity and characteristics of the oral microbiome influenced by race and ethnicity

Periodontitis disproportionately affects racial/ethnic populations. Besides social determinants contributing to disparities in periodontal health, variations of oral microbial communities may also be a key factor influencing oral immune responses. To characterize the oral microbiome from different racial/ethnic populations, we collected 161 dental plaque samples from African Americans (AAs), Caucasian Americans (CAs), and Hispanic Americans (HAs) with clinical gingival health or biofilm-induced gingivitis on an intact periodontium. Using metagenomic sequencing, we found significant difference in diversity and abundance of microbial taxa in the dental plaque samples from AA, CA, and HA groups and unique microbial species that can only be detected in a particular racial/ethnic group. Moreover, we revealed racial/ethnic associated variations in functional potential of the oral microbiome, showing that diversity and abundance of antibiotic resistant genes were greater in the oral microbiome of the AAs than those in CAs or HAs, and that the AAs exhibited higher levels of genes involving in modification of glycoconjugates, oligo- and polysaccharides. These findings indicate more complex and higher virulence potential oral microbiome in AA and HA populations, which likely contributes to higher prevalence of periodontitis in AAs and HAs. ImportanceRecognizing the variations in the oral microbiome among racial/ethnic populations offers insight into the microbial determinants contributing to oral health disparities. In the study presented here, we found a higher level of bleeding on probing (BOP), an indicator of tissue inflammatory response, in the AA group, which is correspondence with a more complex oral microbiome detected in this group. Our observations suggest that the variations of the oral microbiome associated with racial/ethnic backgrounds may directly relate to their virulence potential including their abilities to induce host immune responses and to resist antibiotic treatment. Therefore, these finding can be a stepping stone for developing precision medicine and personalized periodontal prevention/treatment and for reducing oral health disparities.

microbiology↗

bioRxiv2023

Three-dimensional electro-neural interfaces electroplated on subretinal prostheses

ObjectiveHigh-resolution retinal prosthetics offer partial restoration of sight to patients blinded by retinal degenerative diseases through electrical stimulation of the remaining neurons. Decreasing the pixel size enables an increase in prosthetic visual acuity, as demonstrated in animal models of retinal degeneration. However, scaling down the size of planar pixels is limited by the reduced penetration depth of the electric field in tissue. We investigate 3-dimensional structures on top of the photovoltaic arrays for enhanced penetration of electric field to permit higher-resolution implants. ApproachWe developed 3D COMSOL models of subretinal photovoltaic arrays that accurately quantify the device electrodynamics during stimulation and verified it experimentally through comparison with the standard (flat) photovoltaic arrays. The models were then applied to optimise the design of 3D electrode structures (pillars and honeycombs) to efficiently stimulate the inner retinal neurons. The return electrodes elevated on top of the honeycomb walls surrounding each pixel orient the electric field inside the cavities vertically, aligning it with bipolar cells for optimal stimulation. Alternatively, pillars elevate the active electrode into the inner nuclear layer, improving proximity to the target neurons. Modelling results informed a microfabrication process of electroplating the 3D electrode structures on top of the existing flat subretinal prosthesis. Main resultsSimulations demonstrate that despite the conductive sidewalls of the 3D electrodes being exposed to electrolyte, most of the charge flows via the high-capacitance sputtered Iridium Oxide film that caps the top of the 3D structures. The 24 {micro}m height of the electroplated honeycomb structures was optimised for integration with the inner nuclear layer cells in rat retina, while 35 {micro}m height of the pillars was optimized for penetrating the debris layer in human patients. Release from the wafer and implantation of the 3D arrays demonstrated that they are mechanically robust to withstand the associated forces. Histology demonstrated successful integration of the 3D structures with the rat retina in-vivo. SignificanceElectroplated 3D honeycomb structures produce a vertically oriented electric field that offers low stimulation threshold, high spatial resolution and high contrast for the retinal implants with pixel sizes down to 20{micro}m in width. Pillar electrodes offer an alternative configuration for extending the stimulation past the debris layers. Electroplating of the 3D structures is compatible with the fabrication process of the flat photovoltaic arrays, thereby enabling much more efficient stimulation than in their original flat configuration.

neuroscience↗

bioRxiv2022

Pixel size limit of the PRIMA implants: from humans to rodents and back

ObjectiveRetinal prostheses aim at restoring sight in patients with retinal degeneration by electrically stimulating the inner retinal neurons. Clinical trials with patients blinded by atrophic Age-related Macular Degeneration (AMD) using the PRIMA subretinal implant, a 2x2 mm array of 100m-wide photovoltaic pixels, have demonstrated a prosthetic visual acuity closely matching the pixel size. Further improvement in resolution requires smaller pixels, which necessitates more intense stimulation. ApproachHere, we examine the lower limit of the pixel size for PRIMA implants by modeling the electric field, leveraging the clinical benchmarks, as well as using a preclinical animal data to assess the stimulation strength and contrast of various patterns. Visually evoked potentials were measured in RCS rats with photovoltaic implants of 100 and 75m pixels and compared to clinical thresholds with 100 m pixels. Electrical stimulation model calibrated by these clinical and rodent data was used to predict the performance of the implant with smaller pixels. Main ResultsWe found that PRIMA implants with 75m pixels under the maximum safe near-infrared (880nm) illumination of 8 mW/mm2 with 30% duty cycle (10ms pulses at 30Hz) should provide a similar perceptual brightness as with 100 m pixels under 3 mW/mm2 irradiance, used in the current clinical trials. Contrast of the Landolt C pattern scaled down to 75m pixels is also similar under such illumination to that with 100m pixels in clinical settings, increasing the maximum acuity from 20/420 to 20/300. SignificanceComputational model of the photovoltaic subretinal prosthesis defines the minimum pixel size of the PRIMA implants as 75m. Increasing the implant width from 2 to 3 mm and reducing the pixel size from 100 to 75m will nearly quadrupole the number of pixels and thereby should significantly improve the visual performance. Smaller pixels of the same bipolar flat geometry would require excessively intense illumination, and therefore a different pixel design should be considered for further improvement in resolution.

bioengineering↗

bioRxiv2021

Electronic "photoreceptors" enable prosthetic vision with acuity matching the natural resolution in rats

Localized stimulation of the inner retinal neurons for high-acuity prosthetic vision requires small pixels and minimal cross-talk from neighboring electrodes. Local return electrodes within each pixel limit crosstalk, but can over-constrain the electric field, thus precluding efficient stimulation with subretinal pixels smaller than 50 m. Here we demonstrate high-resolution prosthetic vision based on a novel design of a photovoltaic array, where field confinement is achieved dynamically, leveraging the adjustable conductivity of the diodes under forward bias to turn the designated pixels into transient returns. We validated computational modeling of the field confinement in such an optically-controlled circuit by ex-vivo and in-vivo measurements. Most importantly, using this strategy, we demonstrated that the grating acuity with 40 m pixels matches the pixel pitch, while with 20 m pixels, it reaches the 28 m limit of the natural visual resolution in rats. This method enables customized field shaping based on individual retinal thickness and distance from the implant, paving the way to prosthetic vision with acuity as high as 20/80 in atrophic macular degeneration.

bioengineering↗

bioRxiv2020

Vertical-junction Photodiodes for High-resolution Retinal Prostheses

ObjectiveTo restore central vision in patients with atrophic age-related macular degeneration, we replace the lost photoreceptors with photovoltaic pixels, which convert light into current and stimulate the secondary retinal neurons. Clinical trials demonstrated prosthetic acuity closely matching the sampling limit of the 100 m pixels, and hence smaller pixels are required for improving visual acuity. However, with smaller flat bipolar pixels, the electric field penetration depth and the photodiode responsivity significantly decrease, making the device inefficient. Smaller pixels may be enabled (1) by increasing the diode responsivity using vertical p-n junctions and (2) by directing the electric field vertically using 3-D electrodes. Here, we demonstrate such novel photodiodes and test the retinal stimulation in a vertical electric field. ApproachArrays of silicon photodiodes of 55, 40, 30, and 20 m in width, with vertical p-n junctions, were fabricated. The electric field in the retina was directed vertically by a common return electrode at the edge of the devices. Optical and electronic performance of the diodes was characterized in-vitro, and retinal stimulation threshold measured by recording the visually evoked potentials (VEPs) in rats with retinal degeneration. Main resultsThe photodiodes exhibited sufficiently low dark current (<10 pA) and responsivity at 880 nm wavelength as high as 0.51 A/W, with 85% internal quantum efficiency, independent of pixel size. Field mapping in saline demonstrated uniformity of the pixel performance in the array. The full-field stimulation threshold was as low as 0.057{+/-}0.029 mW/mm2 with 10 ms pulses, independent of pixel size. SignificancePhotodiodes with vertical p-n junctions demonstrated excellent charge collection efficiency independent of pixel size, down to 20 m. Vertically-oriented electric field provides a stimulation threshold that is independent of pixel size. These results are the first steps in validation of the feasibility of scaling down the photovoltaic pixels for subretinal stimulation.

bioengineering↗