scholarly journals Electro-mechanical Lung Simulator Using Polymer and Organic Human Lung Equivalents for Realistic Breathing Simulation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Richard Pasteka ◽  
Mathias Forjan ◽  
Stefan Sauermann ◽  
Andreas Drauschke

AbstractSimulation models in respiratory research are increasingly used for medical product development and testing, especially because in-vivo models are coupled with a high degree of complexity and ethical concerns. This work introduces a respiratory simulation system, which is bridging the gap between the complex, real anatomical environment and the safe, cost-effective simulation methods. The presented electro-mechanical lung simulator, xPULM, combines in-silico, ex-vivo and mechanical respiratory approaches by realistically replicating an actively breathing human lung. The reproducibility of sinusoidal breathing simulations with xPULM was verified for selected breathing frequencies (10–18 bpm) and tidal volumes (400–600 ml) physiologically occurring during human breathing at rest. Human lung anatomy was modelled using latex bags and primed porcine lungs. High reproducibility of flow and pressure characteristics was shown by evaluating breathing cycles (nTotal = 3273) with highest standard deviation |3σ| for both, simplified lung equivalents ($${{\boldsymbol{\mu }}}_{\dot{{\bf{V}}}}$$µV̇ = 23.98 ± 1.04 l/min, μP = −0.78 ± 0.63 hPa) and primed porcine lungs ($${{\boldsymbol{\mu }}}_{\dot{{\bf{V}}}}$$µV̇ = 18.87 ± 2.49 l/min, μP = −21.13 ± 1.47 hPa). The adaptability of the breathing simulation parameters, coupled with the use of porcine lungs salvaged from a slaughterhouse process, represents an advancement towards anatomically and physiologically realistic modelling of human respiration.

Biosensors ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 174
Author(s):  
Ramzan Ullah ◽  
Karl Doerfer ◽  
Pawjai Khampang ◽  
Faraneh Fathi ◽  
Wenzhou Hong ◽  
...  

Proper ventilation of a patient with an endotracheal tube (ETT) requires proper placement of the ETT. We present a sensitive, noninvasive, operator-free, and cost-effective optical sensor, called Opt-ETT, for the real-time assessment of ETT placement and alerting of the clinical care team should the ETT become displaced. The Opt-ETT uses a side-firing optical fiber, a near-infrared light-emitting diode, two photodetectors with an integrated amplifier, an Arduino board, and a computer loaded with a custom LabVIEW program to monitor the position of the endotracheal tube inside the windpipe. The Opt-ETT generates a visual and audible warning if the tube moves over a distance set by the operator. Displacement prediction is made using a second-order polynomial fit to the voltages measured from each detector. The system is tested on ex vivo porcine tissues, and the accuracy is determined to be better than 1.0 mm. In vivo experiments with a pig are conducted to test the performance and usability of the system.


Blood ◽  
1996 ◽  
Vol 87 (12) ◽  
pp. 5095-5103 ◽  
Author(s):  
G Hortelano ◽  
A Al-Hendy ◽  
FA Ofosu ◽  
PL Chang

A potentially cost-effective strategy for gene therapy of hemophilia B is to create universal factor IX-secreting cell lines suitable for implantation into different patients. To avoid graft rejection, the implanted cells are enclosed in alginate-polylysine-alginate microcapsules that are permeable to factor IX diffusion, but impermeable to the hosts' immune mediators. This nonautologous approach was assessed by implanting encapsulated mouse myoblasts secreting human factor IX into allogeneic mice. Human factor IX was detected in the mouse plasma for up to 14 days maximally at approximately 4 ng/mL. Antibodies to human factor IX were detected after 3 weeks at escalating levels, which were sustained throughout the entire experiment (213 days). The antibodies accelerated the clearance of human factor IX from the circulation of the implanted mice and inhibited the detection of human factor IX in the mice plasma in vitro. The encapsulated myoblasts retrieved periodically from the implanted mice up to 213 days postimplantation were viable and continued to secrete human factor IX ex vivo at undiminished rates, hence suggesting continued factor IX gene expression in vivo. Thus, this allogeneic gene therapy strategy represents a potentially feasible alternative to autologous approaches for the treatment of hemophilia B.


1990 ◽  
Vol 36 (8) ◽  
pp. 1552-1556 ◽  
Author(s):  
J R Hall

Abstract Critical-care medicine today is practiced by anesthesiologists, internists, pediatricians, and surgeons. Outcome from today's management of critically ill patients is very good, yet associated costs are very high. Over one-half of the hospital costs of critically ill patients emanates from the intensive-care unit (ICU), although the ICU stay accounts for less than 20% of their time in the hospital. Outside of the operating room, the ICU is the most expensive location for patient care in the hospital, and laboratory tests are the most expensive single item. Plans for cost containment should incorporate the following: more effective data management, education of practitioners about appropriateness and costs of tests, conversion from laboratory measurements to appropriate in vivo and ex vivo measurements, and real-time utilization assessment. To provide high-quality, cost-effective critical care in the future, laboratorians and clinicians must work together today to meet the challenges of technology, data management, and staff education.


2016 ◽  
Vol 09 (05) ◽  
pp. 1650046 ◽  
Author(s):  
Xiangqian Hong ◽  
Vivek K. Nagarajan ◽  
Dale H. Mugler ◽  
Bing Yu

High resolution optical endoscopes are increasingly used in diagnosis of various medical conditions of internal organs, such as the cervix and gastrointestinal (GI) tracts, but they are too expensive for use in resource-poor settings. On the other hand, smartphones with high resolution cameras and Internet access have become more affordable, enabling them to diffuse into most rural areas and developing countries in the past decade. In this paper, we describe a smartphone microendoscope that can take fluorescence images with a spatial resolution of 3.1 [Formula: see text]m. Images collected from ex vivo, in vitro and in vivo samples using the device are also presented. The compact and cost-effective smartphone microendoscope may be envisaged as a powerful tool for detecting pre-cancerous lesions of internal organs in low and middle-income countries (LMICs).


2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Wei-Ting Chang ◽  
Hui-Ming Chen ◽  
Shu-Yi Yin ◽  
Yung-Hsiang Chen ◽  
Chih-Chun Wen ◽  
...  

Dioscoreatuber phytoextracts can confer immunomodulatory activitiesex vivoand improve regeneration of bone marrow cellsin vivo. In present study, we evaluated specificDioscoreaphytoextracts for useex vivoas a bone-marrow-derived dendritic cell- (DC-) based vaccine adjuvant for cancer immunotherapy. FractionatedDioscoreaextracts (DsII) were assayed for their effect on maturation and functions of DCex vivoand antimelanoma activity of DC-based vaccinein vivo. The phytoextract from 50–75% ethanol-precipitated fraction ofDioscorea alatavar.purpureaTainung no. 5 tuber, designated as DsII-TN5, showed a strong augmentation of tumor cell lysate- (TCL-) loaded DC-mediated activation of T-cell proliferation. DsII-TN5 stimulated the expression of CD40, CD80, CD86, and IL-1βin TCL-loaded DCs and downregulated the expression of TGF-β1. DC vaccines prepared by a specific schema (TCL (2 h) + LPS (22 h)) showed the strongest antitumor activity. DsII-TN5 as a DC vaccine adjuvant showed strong antimelanoma activity and reduced myeloid-derived suppressor cell (MDSC) population in tested mice. DsII-TN5 can also activate DCs to enhance Th1- and Th17-related cytokine expressions. Biochemical analysis showed that DsII-TN5 consists mainly of polysaccharides containing a high level (53%) of mannose residues. We suggest that DsII-TN5 may have potential for future application as a potent, cost-effective adjuvant for DC-based cancer vaccines.


2021 ◽  
Author(s):  
Qiu Meiyu ◽  
Li Pei

Clustered regularly interspaced short palindromic repeats (CRISPR) technology, an easy, rapid, cost-effective, and precise gene-editing technique, has revolutionized diagnostics and gene therapy. Fast and accurate diagnosis of diseases is essential for point-of-care-testing (POCT) and specialized medical institutes. The CRISPR-associated (Cas) proteins system shed light on the new diagnostics methods at point-of-care (POC) owning to its advantages. In addition, CRISPR/Cas-based gene-editing technology has led to various breakthroughs in gene therapy. It has been employed in clinical trials for a variety of untreatable diseases, including cancer, blood disorders, and other syndromes. Currently, the clinical application of CRISPR/Cas has been mainly focused on ex vivo therapies. Recently, tremendous efforts have been made in the development of ex vivo gene therapy based on CRISPR-Cas9. Despite these efforts, in vivo CRISPR/Cas gene therapy is only in its initial stage. Here, we review the milestones of CRISPR/Cas technologies that advanced the field of diagnostics and gene therapy. We also highlight the recent advances of diagnostics and gene therapy based on CRISPR/Cas technology. In the last section, we discuss the strength and significant challenges of the CRISPR/Cas technology for its future clinical usage in diagnosis and gene therapy.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 117-117
Author(s):  
Ami Patel ◽  
Manisha Kintali ◽  
Gohar Mosoyan ◽  
Ronald Hoffman ◽  
Camelia Iancu-Rubin

Abstract The demand for platelet (PTL) transfusions has steadily increased, straining a supply that is limited by its dependency on donors, short lifespan, risk of infections and alloimmunization. This stimulated the search for alternative PTL sources including PTLs generated ex vivo from primary CD34+ cells and immortalized pluripotent stem cells. These approaches, however, are associated with obstacles such as scalability and encounter identical limitations as donor PTLs: short shelf life, storage at ambient temperature and limited lifespan after infusion. These obstacles lead us to focus our efforts on not producing PLTs but rather a cryopreservable cell product consisting of megakaryocytes (MK) that can produce PTLs after transfusion into patients. Umbilical cord blood units (CBU) are readily available sources for stem cell for transplantation. We created an efficient and cost effective culture system in which CB-derived CD34+ cells are first expanded then allowed to mature into MKs. Initially, we determined the optimal culture period (10-11 days) resulting in the greatest number of CD41+/CD42b- and CD41+/CD42b+ MKs which are capable of PTL production. Next, we used research and clinical grade CBU to generate clinically relevant doses of MK. The median number of CD34+ cells selected from one CBU was 2.5x106 with a purity of 90% (n=4). Following expansion and MK maturation, these cells generated 5.8x107 viable total nucleated cells (TNC)/CBU. Out of these, 3.3 x 107 were CD41+ MKs which corresponds to a median cell dose of 4.1x105 CD41+ cells/Kg of body weight. 92% of CD41+ MKs were mature CD42b+ cells which we previously showed that are capable of ex vivo platelet production. Finally, we performed clonogenic assays and found that one CBU can generate ~1.5x106 CFU-MK. One half of these MK-biased cultures was characterized and assessed immediately after culture and the other half was cryopreserved. The fresh product was infused into sublethally irradiated NSG mice and the presence of human PTLs in the mouse peripheral blood (mPB) was evaluated weekly for 8 weeks at which time the animals were also analyzed for hMK chimerism in the bone marrow (BM), spleen (SP) and lung. The results demonstrate that 87% of animals (13 out of 15) had a robust hPTLs population in their PB. hPTL were detected as early as week 1 post infusion and their number peaked on week 4 (median, 6x103 hPTL/μl) after which it plateaued. The release of hPTL in the mPB was accompanied by the presence of hCD41+ MKs in the mBM, SP and the lung indicating that the infused cells provided both early hPTL release and a reservoir of MK precursors for continuous hPTL production. We also found that in addition to MKs, these same organs contained hCD34+, CD45+ and myeloid CD15+ cells. These findings underscore the capabilities of this product which might have broader clinical applicability such as utilization during myeloablative or suppressive chemo/radiotherapy to improve the time and duration for both neutrophil and platelet engraftment. Equally important, we provide novel evidence that the lung is a site for hMK engraftment after transplantation, in line with recent reports recognizing the pulmonary bed as site for platelet production in the mouse. The major advantage of developing a MK-based product over ex vivo generated PTLs is the amenability of the former to cryopreservation thus becoming a readily available cellular therapy which would be amenable to stock-piling. Therefore, portions of the same MK products described above were cryopreserved then subjected to ex vivo and in vivo studies identical to these performed on their fresh counterparts. Following thawing, the average recovery rate was 71% for TNC and 74.3% for CD41+ cells. MK phenotype and morphology as well as the number CFU-MK generated ex vivo were identical to that found in the fresh product. Although the number of TNC in the thawed product was lower than that of its fresh counterpart, the number of hPTL detected after its infusion ranged from 0.4 to 20.5x103 hPTL/μl which is comparable to that detected after infusion of the fresh equivalent, 0.7-16x103 hPTL/μl. In summary, we created a potent transfusable MK cell product that provides robust and sustained PTL and hematopoietic engraftment in vivo and maintains this capability after cryopreservation. Clinical development of such product is now being pursued for the treatment of thrombocytopenia in acute leukemia patients undergoing chemotherapy. Disclosures Hoffman: Summer Road: Research Funding; Janssen: Research Funding; Formation Biologics: Research Funding; Merus: Research Funding; Incyte: Research Funding. Iancu-Rubin:Incyte: Research Funding; Merck: Research Funding; Summer Road, LLC: Research Funding; Formation Biologics: Research Funding.


2021 ◽  
Author(s):  
Les Bogdanowicz ◽  
Onur Fidaner ◽  
Donato Ceres ◽  
Alex Grycuk ◽  
David Demos

UNSTRUCTURED Lung cancer is the world’s leading cause of cancer deaths, and diagnosis remains challenging. Lung cancer starts as small nodules; early and accurate diagnosis allows timely surgical resection of malignant nodules while avoiding unnecessary surgery in patients with benign nodules. The Cole Relaxation Frequency (CRF) is a derived electrical bioimpedance signature, which may be utilized to distinguish cancerous tissues from normal tissues. Here we show that CRF allows for diagnosis of cancer in human subjects, based on evaluation of 60 specimens obtained from 30 patients. We observed clear discrimination of CRF values in tumor and distant normal tissues, resulting in a high degree of sensitivity (97%) and specificity (87%) in cancer diagnosis. Furthermore, we tested 20 xenograft small animal model specimens, observing a similar separation of CRF values as in the human in-vivo measurements. We also obtained CRF measurements in pressurized and unpressurized lungs by implanting tumors into ex-vivo porcine lungs. CRF measurements align with previous tests in human and small animal models.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yoann Montigaud ◽  
Quentin Georges ◽  
Jérémie Pourchez ◽  
Lara Leclerc ◽  
Clémence Goy ◽  
...  

AbstractIn intensive care units, nebulization is a usual route for drug administration to patients under mechanical ventilation (MV). The effectiveness of inhalation devices as well as depositions sites of aerosols for ventilated patients remain poorly documented. In vivo human inhalation studies are scarce due to ethical restrictions because imaging techniques require radioaerosols to assess regional aerosol deposition. Thus, we developed an ex vivo respiratory model under invasive MV for preclinical aerosol deposition studies. The model was composed of ex vivo porcine respiratory tracts. MV was achieved thanks to a tracheal intubation and a medical ventilator under controlled conditions. Respiratory features were studied using analogical sensors. Then regional homogeneity of gas-ventilation was assessed with 81mKrypton scintigraphies. Finally, a proof of concept study for aerosol deposition was performed. Obtained respiratory features as well as gamma-imaging techniques, which demonstrated a homogenous regional ventilation and about 18% ± 4% of the nebulized dose deposited the respiratory tract, were in good agreement with human data available in the literature. This original ex vivo respiratory model provides a feasible, reproducible and cost-effective preclinical tool to achieve aerosol deposition studies under MV.


2020 ◽  
Vol 319 (4) ◽  
pp. C675-C693
Author(s):  
Kalpaj R. Parekh ◽  
Janna Nawroth ◽  
Albert Pai ◽  
Shana M. Busch ◽  
Christiana N. Senger ◽  
...  

The ability to replace defective cells in an airway with cells that can engraft, integrate, and restore a functional epithelium could potentially cure a number of lung diseases. Progress toward the development of strategies to regenerate the adult lung by either in vivo or ex vivo targeting of endogenous stem cells or pluripotent stem cell derivatives is limited by our fundamental lack of understanding of the mechanisms controlling human lung development, the precise identity and function of human lung stem and progenitor cell types, and the genetic and epigenetic control of human lung fate. In this review, we intend to discuss the known stem/progenitor cell populations, their relative differences between rodents and humans, their roles in chronic lung disease, and their therapeutic prospects. Additionally, we highlight the recent breakthroughs that have increased our understanding of these cell types. These advancements include novel lineage-traced animal models and single-cell RNA sequencing of human airway cells, which have provided critical information on the stem cell subtypes, transition states, identifying cell markers, and intricate pathways that commit a stem cell to differentiate or to maintain plasticity. As our capacity to model the human lung evolves, so will our understanding of lung regeneration and our ability to target endogenous stem cells as a therapeutic approach for lung disease.


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