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Low-dose intrapulmonary drug delivery device for studies on next-generation therapeutics in mice

Journal of Controlled Release 2023年第1期359卷 287-301页

作者： Gracioso Martins, Ana Maria Snider, Douglas B. Popowski, Kristen D. Schuchard, Karl G. Tenorio, Matias Akunuri, Sandip Wee, Junghyun Peters, Kara J. Jansson, Anton Shirwaiker, Rohan Cheng, Ke Freytes, Donald O. Cruse, Glenn P. Department of Molecular Biomedical Sciences College of Veterinary Medicine North Carolina State University RaleighNC United States Comparative Medicine and Translational Research Training Program North Carolina State University RaleighNC United States Comparative Medicine Institute North Carolina State University RaleighNC United States Joint Department of Biomedical Engineering College of Engineering North Carolina State University & University of North Carolina-Chapel Hill NC United States Edward P. Fitts Department of Industrial and Systems Engineering North Carolina State University RaleighNC United States Department of Mechanical and Aerospace Engineering North Carolina State University RaleighNC United States Analytical Instrumentation Facility Monteith Research Center North Carolina State University RaleighNC United States

Although nebulizers have been developed for delivery of small molecules in human patients, no tunable device has been purpose-built for targeted delivery of modern large molecule and temperature-sensitive therapeutics to mice. Mice are used most of all species in biomedical research and have the highest number of induced models for human-relevant diseases and transgene models. Regulatory approval of large molecule therapeutics, including antibody therapies and modified RNA highlight the need for quantifiable dose delivery in mice to model human delivery, proof-of-concept studies, efficacy, and dose-response. To this end, we developed and characterized a tunable nebulization system composed of an ultrasonic transducer equipped with a mesh nebulizer fitted with a silicone restrictor plate modification to control the nebulization rate. We have identified the elements of design that influence the most critical factors to targeted delivery to the deep lungs of BALB/c mice. By comparing an in silico model of the mouse lung with experimental data, we were able to optimize and confirm the targeted delivery of over 99% of the initial volume to the deep portions of the mouse lung. The resulting nebulizer system provides targeted lung delivery efficiency far exceeding conventional nebulizers preventing waste of expensive biologics and large molecules during proof-of-concept and pre-clinical experiments involving mice. (Word Count =207). © 2023 Elsevier B.V.

关键词： Molecules

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Scalable Stereolithography-Based Monolithic Microfluidic Device Creation for Rapid Biological Sample Analyses 25

Scalable Stereolithography-Based Monolithic Microfluidic Dev...

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25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021

作者： Markoski, Alex Wong, Ian Y. Borenstein, Jeffrey T. Department of Synthetic Biology and Bio Instrumentation Draper Bioengineering Division CambridgeMA United States School of Engineering Center for Biomedical Engineering Joint Program in Cancer Biology Brown University ProvidenceRI United States

ISBN: (纸本)9781733419031

Microfluidic manipulation and perfusion of multicellular spheroids often utilize device geometries with relatively large channels but smaller trapping features, which are tricky to fabricate with robust bonding. Here, we demonstrate one-step light-directed 3D printing of a sealed monolithic device with enclosed channels and pillar arrays, which we validate for capturing and imaging multicellular spheroids in varying flow. Our approach links computer-aided design with finite element simulations of flow and oxygen conditions, which were experimentally realized. We envision these design and fabrication approaches may be useful in generating rapidly designed multiplexed monolithic arrays for preclinical drug testing in cancer. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

关键词： Microfluidics

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Subcellular Composition Based On Light-Element EELS

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Microscopy and Microanalysis 2020年第S2期3卷 927-928页

作者： R.D. Leapman Biomedical Engineering & Instrumentation Program NCRR National Institutes of Health Bethesda MD 20892.

Recent work on biological electron energy-loss spectroscopy (EELS) in the analytical electron microscope has focused on measuring concentrations of the important elements, calcium and phosphorus. Analysis of the light elements, for which EELS was originally thought to be best suited, has so far not yielded much useful information from biological specimens. Whereas low-loss fine structure has been analyzed successfully to measure distributions of water and protein in frozen-hydrated cells, core-edge fine structure cannot be recorded at sufficiently low dose to obtain useful chemical information. However, the atomic ratios of the light elements (carbon, nitrogen and oxygen) obtained from EELS are less dependent on electron dose. Together with sulfur (in proteins) and phosphorus (in nucleic acids, phospholipids and phosphates) these ratios can help determine the types and proportions of compounds that are present at the subcellular level. Here we re-examine the potential for making these kinds of measurements.

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Capabilities and Limitations of Biological Electron Energy-Loss Spectroscopy

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Microscopy and Microanalysis 2020年第S2期3卷 871-872页

作者： R.D. Leapman S.B. Andrews Biomedical Engineering & Instrumentation Program NCRR Bethesda MD 20892. Laboratory of Neurobiology NINDS National Institutes of HealthBethesda MD 20892.

Perhaps the ultimate aim of analytical electron microscopy in biology is to detect single atoms or ions bound to isolated macromolecular assemblies and small cellular organelles rapidly frozen in their native state. Although the meaningful spatial resolution in such analyses is limited to ∽10 nm or more by radiation damage, the high intrinsic sensitivity of electron energy-loss spectroscopy (EELS) coupled with recent developments seems to make this rather ambitious goal—originally proposed some twenty years ago—within reach. Here we describe examples where EELS has been able to detect surprisingly small numbers of atoms in biological specimens and discuss some fundamental limits that are encountered as well as some possible strategies for circumventing these *** our laboratory we have used a scanning transmission electron microscope (STEM) equipped with a field-emission source and parallel-detection EELS because the probe size and collection efficiency of this instrument are optimized to give the lowest detectable number of atoms and lowest detectable atomic fraction.

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From Challenges and Pitfalls to Recommendations and Opportunities: Implementing Federated Learning in Healthcare

arXiv

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arXiv 2024年

作者： Li, Ming Xu, Pengcheng Hu, Junjie Tang, Zeyu Yang, Guang Bioengineering Department Imperial-X Imperial College London LondonW12 7SL United Kingdom National Heart and Lung Institute Imperial College London LondonSW7 2AZ United Kingdom Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital BostonMA United States State Key Laboratory of Extreme Photonics and Instrumentation College of Optical Science and Engineering Zhejiang University Hangzhou China Tri-Institutional Computational Biology & Medicine Program Weill Cornell Medicine of Cornell University New York United States Cardiovascular Research Centre Royal Brompton Hospital LondonSW3 6NP United Kingdom School of Biomedical Engineering & Imaging Sciences King’s College London LondonWC2R 2LS United Kingdom

Federated learning holds great potential for enabling large-scale healthcare research and collaboration across multiple centres while ensuring data privacy and security are not compromised. Although numerous recent studies suggest or utilize federated learning based methods in healthcare, it remains unclear which ones have potential clinical utility. This review paper considers and analyzes the most recent studies up to May 2024 that describe federated learning based methods in healthcare. After a thorough review, we find that the vast majority are not appropriate for clinical use due to their methodological flaws and/or underlying biases which include but are not limited to privacy concerns, generalization issues, and communication costs. As a result, the effectiveness of federated learning in healthcare is significantly compromised. To overcome these challenges, we provide recommendations and promising opportunities that might be implemented to resolve these problems and improve the quality of model development in federated learning with healthcare. © 2024, CC BY-NC-ND.

关键词： Federated learning

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Obesity-driven changes in breast tissue exhibit a pro-angiogenic extracellular matrix signature

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Matrix Biology Plus 2024年 24卷 100162页

作者： Bamberg, Ellen E. Maslanka, Mark Vinod-Paul, Kiran Sams, Sharon Pollack, Erica Conklin, Matthew Kabos, Peter Hansen, Kirk C. Department of Medicine Division of Medical Oncology University of Colorado Anschutz Medical Campus Aurora CO United States Department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus Aurora CO United States Department of Pathology University of Colorado Anschutz Medical Campus Aurora CO United States Department of Radiology and Medical Imaging University of Colorado Anschutz Medical Campus Aurora CO United States Department of Cell and Regenerative Biology School of Medicine and Public Health Carbone Cancer Center (Tumor Microenvironment Program) University of Wisconsin Madison WI United States Laboratory for Optical and Computations Instrumentation Department of Biomedical Engineering University of Wisconsin-Madison Madison WI United States

Obesity has reached epidemic proportions in the United States, emerging as a risk factor for the onset of breast cancer and a harbinger of unfavorable outcomes [1–3]. Despite limited understanding of the precise mechanisms, both obesity and breast cancer are associated with extracellular matrix (ECM) rewiring [4–6]. Utilizing total breast tissue proteomics, we analyzed normal-weight (18.5 to < 25 kg/m²), overweight (25 to < 30 kg/m²), and obese (≥30 kg/m²) individuals to identify potential ECM modifying proteins for cancer development and acceleration. Obese individuals exhibited substantial ECM alterations, marked by increased basement membrane deposition, angiogenic signatures, and ECM-modifying proteins. Notably, the collagen IV crosslinking enzyme peroxidasin (PXDN) emerged as a potential mediator of the ECM changes in individuals with an elevated body mass index (BMI), strongly correlating with angiogenic and basement membrane signatures. Furthermore, glycan-binding proteins galectin-1 (LGALS1) and galectin-3 (LGALS3), which play crucial roles in matrix interactions and angiogenesis, also strongly correlate with ECM modifications. In breast cancer, elevated PXDN, LGALS1, and LGALS3 correlate with reduced relapse-free and distant-metastatic-free survival. These proteins were significantly associated with mesenchymal stromal cell markers, indicating adipocytes and fibroblasts may be the primary contributors of the obesity-related ECM changes. Our findings unveil a pro-angiogenic ECM signature in obese breast tissue, offering potential targets to inhibit breast cancer development and progression. © 2024

关键词： Adipocytes Body Mass Index Breast Extracellular matrix Fibroblasts Galectin LGALS1 LGALS3 Obesity Peroxidasin PXDN Stromal cells Tissue Proteomics Tumor Microenvironment

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Highly accelerated EPI with wave encoding and multi-shot simultaneous multi-slice imaging

arXiv

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arXiv 2021年

作者： Cho, Jaejin Liao, Congyu Tian, Qiyuan Zhang, Zijing Xu, Jinmin Lo, Wei-Ching Poser, Benedikt A. Stenger, V. Andrew Stockmann, Jason Setsompop, Kawin Bilgic, Berkin Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital BostonMA United States Harvard Medical School BostonMA United States Radiological Sciences Laboratory Stanford University Palo AltoCA United States State Key Laboratory of Modern Optical Instrumentation College of Optical Science and Engineering Zhejiang University Hangzhou China Siemens Medical Solutions BostonMA United States Maastricht Brain Imaging Centre Maastricht University Maastricht Netherlands MR Research Program Department of Medicine John A. Burns School of Medicine University of Hawai'i HI United States Harvard-MIT Health Sciences and Technology Massachusetts Institute of Technology CambridgeMA United States

Purpose: To introduce wave encoded acquisition and reconstruction techniques for highly accelerated echo planar imaging (EPI) with reduced g-factor penalty and image artifacts. Method: Wave-EPI involves playing sinusoidal gradients during the EPI readout while employing interslice shifts as in blipped-CAIPI acquisitions. This spreads the aliasing in all spatial directions, thereby taking better advantage of 3D coil sensitivity profiles. The amount of voxel spreading that can be achieved by the wave gradients during the short EPI readout period is constrained by the slew rate of the gradient coils and peripheral nerve stimulation (PNS) monitor. We propose to use a "half-cycle" sinusoidal gradient to increase the amount of voxel spreading that can be achieved while respecting the slew and stimulation constraints. Extending wave-EPI to multi-shot acquisition minimizes geometric distortion and voxel blurring at high in-plane resolution, while structured low-rank regularization mitigates shot-to-shot phase variations without additional navigators. We propose to use different point spread functions (PSFs) for the k-space lines with positive and negative polarities, which are calibrated with a FLEET-based reference scan and allow for addressing gradient imperfections. Results: Wave-EPI provided whole-brain single-shot gradient echo (GE) and multi-shot spin echo (SE) EPI acquisitions at high acceleration factors and was combined with g-Slider slab encoding to boost the SNR level in 1mm isotropic diffusion imaging. Relative to blipped-CAIPI, wave-EPI reduced average and maximum g-factors by up to 1.21- and 1.37-fold, respectively. Conclusion: Wave-EPI allows highly accelerated single- and multi-shot EPI with reduced g-factor and artifacts and may facilitate clinical and neuroscientific applications of EPI by improving the spatial and temporal resolution in functional and diffusion imaging. Copyright © 2021, The Authors. All rights reserved.

关键词： Signal encoding

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PID control design and implementation for laboratory scale infant incubator temperature using FOPDT model

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AIP Conference Proceedings 2020年第1期2314卷

作者： Akif Rahmatillah Inten Fauziah Hidayat Alfian Pramudita Putra Osmalina Nur Rahma Suhariningsih 1Medical Instrumentation Laboratory Biomedical Engineering Study Program Faculty of Science & Technology Universitas Airlangga Surabaya Indonesia 2Institute of Tropical Disease (ITD) Universitas Airlangga Surabaya Indonesia

Premature babies have difficulty for regulating their body temperature because weight deficiency. Infant incubator that equipped by temperature control system can support thermoregulation process in baby body. This paper explained design of temperature control system using Proportional-Integral-Derivative (PID) controller and its implementation to the laboratory scale infant incubator. The transfer function of infant incubator was obtained by step test method using First-Order and Dead Time (FOPDT) model where process gain K = 0.29, settling time Ts = 18s and dead time Td = 1. Ziegler-Nichols (ZN) and Direct Synthesis (DS) PID coefficients tuning method was used is this experiment and it resulted for ZN tunning method, proportional gain Kc = 20.14, integration time Ti = 0.2 and derivative time Td = 0.05 and DS tunning method proportional gain Kc = 5, integration time Ti = 18. PID controller was implemented to the Personal Computer (PC) with LabVIEW 2013 programing language, LabJack U3 HV data acquisition device and LM-35 temperature sensor. Set point of temperature that required was 350C with t and 250C initial temperature. The controller performance that resulted by this experiment were for ZN tunning method 38 minutes for settling time while DS tunning method resulted 12 minutes for setling time.

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Design and implementation of multichannel EMG for upper extremity myoelectric signal acquisition using IIR filter

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AIP Conference Proceedings 2020年第1期2314卷

作者： Akif Rahmatillah Amila Sofiah Prihartini Widiyanti 1Medical Instrumentation Laboratory Biomedical Engineering Study Program Faculty of Science & Technology Universitas Airlangga Surabaya Indonesia 2Institute of Tropical Disease (ITD) Universitas Airlangga Surabaya Indonesia

This study aimed at designing and implementing a multichannel EMG based on Infinite Impulse Response (IIR) filter and then compare its performance with the standard EMG devices. Hence, the design of this multichannel EMG system consists of two parts: hardware and software. The hardware comprises instrumentation amplifier and NI DAQ USB 6009 as data acquisition device, while the software is composed of myoelectric signal processing (e.g. filtering, rectifying, and smoothing) and interface signal on personal computer (PC) using LabVIEW programming. To test the device, two procedures were performed, there were instrumentation test and performance test of the EMG device. The instrumentation test resulted in the gain value of instrumentation amplifier at 12.794 times with linearity of 0.9998. Moreover, the response of implemented Butterworth IIR filter is compatible with the design at the cut off frequency of 30-400 Hz and 50 Hz. For the performance test, quantitative and qualitative data recorded from normal male subjects aged of 20-40 were compared. The result showed that EMG prototype work as well as EMG comparison with relative error percentage for each value parameter of maximum, minimum, and average amplitude signals at 14.05885 %, 14.82683 %, and 14.0411 % respectively. Furthermore, the features of recorded signal for similar simultaneous movements using EMG prototype also share identical features with the recorded signal using standard EMG.

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Positive Staining for Improved Contrast Of Macromolecules In Transmission Electron Microscopy

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Microscopy and Microanalysis 2018年第S1期24卷 1730-1731页

作者： Kelly A. Parker Yue Li Adam Eshein Shengshuang Zhu Cheri M. Hampton Lawrence F. Drummy Vinayak P. Dravid Department of Materials Science & Engineering Northwestern University Evanston Illinois60208 Applied Physics Program Northwestern University Evanston Illinois 60208 Department of Biomedical Engineering Northwestern University Evanston Illinois60208 Materials and Manufacturing Directorate Air Force Research Laboratory WPAFB OH45433 Electron Probe Instrumentation Center (EPIC) Facility NUANCE Center Northwestern University Evanston Illinois60208

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