Search

We outline a simple, low-cost design—both scalable and adaptable worldwide—to decontaminate filtering facepiece respirators (FFRs) using ultraviolet bulbs and supplies found in most hardware stores. The setup will help health care workers safely reuse FFRs in light of the shortages during the COVID-19 pandemic., Key Messages Ultraviolet germicidal irradiation (UVGI) systems can be used to decontaminate filtering facepiece respirators that are in short supply during the current COVID-19 pandemic, but are costly and scarce.Custom-built UVGI systems can be easily and affordably created using common items found in hardware stores and within research institutions.Health care workers and administrators should consider this setup as a cost-effective option to combat personal protective equipment (PPE) shortages during the current pandemic.Academic institutions should consider fostering collaborations with local health care institutions to provide idle resources to front line health care workers facing PPE shortages., As the current COVID-19 pandemic illustrates, not all hospitals and other patient care facilities are equipped with enough personal protective equipment to meet the demand in a crisis. Health care workers around the world use filtering facepiece respirators to protect themselves and their patients, yet during this global pandemic they are forced to reuse what are intended to be single-use masks. This poses a significant risk to these health care workers along with the people they are trying to protect. Ultraviolet germicidal irradiation (UVGI) has been validated previously as a method to effectively decontaminate these masks between use. However, not all facilities have access to the expensive commercial ultraviolet type C (UV-C) lamp decontamination equipment required for UVGI. UV-C bulbs are sitting idle in biosafety cabinets at universities and research facilities around the world that have been shuttered to slow the spread of COVID-19. These bulbs may also be available in existing medical centers where infectious diseases are commonly treated. We developed a method to modify existing light fixtures or create custom light fixtures that are compatible with new or existing UV-C bulbs. This system is scalable; can be created for less than US$50, on site and at the point of need; and leverages resources that are currently untapped and sitting unused in public and private research facilities during the pandemic. The freely accessible design can be easily modified for use around the world. Health care facilities can obtain this potentially lifesaving UVGI resource with minimal funds by collaborating with research facilities to obtain the UV-C meters and UV-C bulbs if they are unavailable from other sources. Although mask reuse is not ideal, we must do what we can in emergency situations to protect our health care workers responding to the pandemic and the communities they serve.

COVID-19 is a disease that manifests itself in a multitude of ways across a wide range of tissues. Many factors are involved, and though impressive strides have been made in studying this novel disease in a very short time, there is still a great deal that is unknown about how the virus functions. Clinical data has been crucial for providing information on COVID-19 progression and determining risk factors. However, the mechanisms leading to the multi-tissue pathology are yet to be fully established. Although insights from SARS-CoV-1 and MERS-CoV have been valuable, it is clear that SARS-CoV-2 is different and merits its own extensive studies. In this review, we highlight unresolved questions surrounding this virus including the temporal immune dynamics, infection of non-pulmonary tissue, early life exposure, and the role of circadian rhythms. Risk factors such as sex and exposure to pollutants are also explored followed by a discussion of ways in which bioengineering approaches can be employed to help understand COVID-19. The use of sophisticated in vitro models can be employed to interrogate intercellular interactions and also to tease apart effects of the virus itself from the resulting immune response. Additionally, spatiotemporal information can be gleaned from these models to learn more about the dynamics of the virus and COVID-19 progression. Application of advanced tissue and organ system models into COVID-19 research can result in more nuanced insight into the mechanisms underlying this condition and elucidate strategies to combat its effects.

Background The ability to detect tumor-specific biomarkers in real-time using optical imaging plays a critical role in preclinical studies aimed at evaluating drug safety and treatment response. In this study, we engineered an imaging platform capable of targeting different tumor biomarkers using a multi-colored library of nanoprobes. These probes contain rare-earth elements that emit light in the short-wave infrared (SWIR) wavelength region (900–1700 nm), which exhibits reduced absorption and scattering compared to visible and NIR, and are rendered biocompatible by encapsulation in human serum albumin. The spectrally distinct emissions of the holmium (Ho), erbium (Er), and thulium (Tm) cations that constitute the cores of these nanoprobes make them attractive candidates for optical molecular imaging of multiple disease biomarkers. Methods SWIR-emitting rare-earth-doped albumin nanocomposites (ReANCs) were synthesized using controlled coacervation, with visible light-emitting fluorophores additionally incorporated during the crosslinking phase for validation purposes. Specifically, HoANCs, ErANCs, and TmANCs were co-labeled with rhodamine-B, FITC, and Alexa Fluor 647 dyes respectively. These Rh-HoANCs, FITC-ErANCs, and 647-TmANCs were further conjugated with the targeting ligands daidzein, AMD3100, and folic acid respectively. Binding specificities of each nanoprobe to distinct cellular subsets were established by in vitro uptake studies. Quantitative whole-body SWIR imaging of subcutaneous tumor bearing mice was used to validate the in vivo targeting ability of these nanoprobes. Results Each of the three ligand-functionalized nanoprobes showed significantly higher uptake in the targeted cell line compared to untargeted probes. Increased accumulation of tumor-specific nanoprobes was also measured relative to untargeted probes in subcutaneous tumor models of breast (4175 and MCF-7) and ovarian cancer (SKOV3). Preferential accumulation of tumor-specific nanoprobes was also observed in tumors overexpressing targeted biomarkers in mice bearing molecularly-distinct bilateral subcutaneous tumors, as evidenced by significantly higher signal intensities on SWIR imaging. Conclusions The results from this study show that tumors can be detected in vivo using a set of targeted multispectral SWIR-emitting nanoprobes. Significantly, these nanoprobes enabled imaging of biomarkers in mice bearing bilateral tumors with distinct molecular phenotypes. The findings from this study provide a foundation for optical molecular imaging of heterogeneous tumors and for studying the response of these complex lesions to targeted therapy.

As the current COVID-19 pandemic illustrates, not all hospitals and other facilities are equipped with enough personal protective equipment to meet the demand in a crisis. Healthcare workers around the world utilize N95 masks to protect themselves and their patients, yet during this global pandemic they are forced to re-wear what is intended to be single-use masks. This poses significant risk to these healthcare workers along with the populations they are trying to protect. Ultraviolet germicidal irradiation (UVGI) has been validated previously as a way to effectively sterilize these masks between use, however, not all facilities have access to the high cost commercial UV-C lamp sterilization equipment. However, UV-C bulbs are sitting idle in biosafety cabinets (BSCs) at universities and research facilities around the globe that have been shuttered to slow the spread of COVID-19. These bulbs may also be available in existing medical centers where infectious diseases are commonly treated. Therefore, we have developed a method to modify existing light fixtures, or create custom light fixtures compatible with new or existing common UV-C bulbs. This system is scalable and can be created for less than 50 US dollars, on site, at the point of need, and leverages resources that are currently untapped and sitting unused in public and private research facilities. The freely-accessible design can be easily modified for use around the world. Hospitals can obtain this potentially life-saving UVGI resource with minimal funds, via collaboration between research facilities to obtain the UV-C meters and limited availability UVGI bulbs. While mask reuse is not ideal, we must do what we can in emergency situations to protect our frontline healthcare workers and the communities they serve.

The identification and molecular profiling of early metastases remains a major challenge in cancer diagnostics and therapy. Most in vivo imaging methods fail to detect small cancerous lesions, a problem that is compounded by the distinct physical and biological barriers associated with different metastatic niches. Here, we show that intravenously injected rare-earth-doped albumin-encapsulated nanoparticles emitting short-wave infrared light (SWIR) can detect targeted metastatic lesions in vivo, allowing for the longitudinal tracking of multi-organ metastases. In a murine model of basal human breast cancer, the nanoprobes enabled whole-body SWIR detection of adrenal gland microlesions and bone lesions that were undetectable via contrast-enhanced magnetic resonance imaging (CE-MRI) as early as, respectively, three weeks and five weeks post-inoculation. Whole-body SWIR imaging of nanoprobes functionalized to differentially target distinct metastatic sites and administered to a biomimetic murine model of human breast cancer resolved multi-organ metastases that showed varied molecular profiles at the lungs, adrenal glands and bones. Real-time surveillance of lesions in multiple organs should facilitate pre-therapy and post-therapy monitoring in preclinical settings.

Breast cancer is made up of distinct heterogeneous subpopulations that influence treatment responses. Currently, molecular phenotyping of a tumor involves post-biopsy histology, which makes quantification and assessment of spatial heterogeneity difficult. While there has been moderate success in radiographic imaging of heterogeneity, by PET and MRI, there is an urgent need for non-invasive imaging modalities to quantitatively index tumor heterogeneity in real-time. Our study utilizes rare earth(Re) nanoprobes which absorb near infrared radiation (980nm) and emit in the short wave infrared (SWIR) region (1000- 3000nm), allowing for improved tissue penetration and detection depth. We designed Re nanoprobes encapsulated in albumin to form Rare-Earth Albumin NanoComposites (ReANCs), which can be administered in vivo to target and detect deep tissue microlesions (~18mm3) at a depth of ~1cm. Additionally, ReANCs have been shown to detect multi-organ micro-lesions early and have excellent safety and tolerability profile. Albumin encapsulation not only creates a biocompatible nanoparticle, but also allows for increased biodistribution, pharmacokinetics, and the possibility of functionalization. Most notably, the availability of different Re dopants, Erbium and Thulium, with distinct emission spectral bands allows for accurate indexing of cellular subsets. In this study, we first demonstrate the ability of multi-spectral, ReANCs to distinguish and map a heterogeneous tumor lesion. 3D spheroids made of varying ratios of prelabeled populations of MDA-MB-231 cells (erbium-doped) and HCC1954 (thulium doped) were engineered and imaged to obtain a training set for spatial mapping of the different cell populations. Ratiometric analysis of the spheroids was performed to develop an algorithm for indexing. Subsequently, cancer-targeted ReANCs were engineered and target validation was performed in a 3D spheroid model followed by spatial mapping of targeted populations leading to ratiometric indexing of the different populations. Briefly, erbium doped ReANCs (MDA-MB-231 cells) and thulium doped ReANCs (HCC1954 cells), were deployed to detect distinct subpopulations in a 3D heterogeneous spheroid model of Her2+/- breast cancer. Images were obtained using in vitro microscopy platforms, using 980 nm excitation sources. Separate band-pass filters isolated emissions from the distinct REANC dopants, allowing for quantification of each pre-labeled cell in the training set. This was followed by development of an algorithm to find the percentage of subsets with unknown proportions allowing indexing of unknown subsets in a single tumor spheroid. This novel in vivo imaging modality forms the early basis for real-time on molecular aspects of the tumor and real-time tumor response tracking. Citation Format: Harini Kantamneni, Michael Donzanti, Xinyu Zhao, Shuqing He, Mei Chee Tan, Mark Pierce, Charles M. Roth, Shridar Ganesan, Vidya Ganapathy, Prabhas V. Moghe. Spatial mapping and molecular phenotyping of heterogeneous breast cancer lesions with multi-spectral short wave infrared emitting rare-earth nanoprobes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4119.