The Applications and Challenges of the Development of In Vitro Tumor Microenvironment Chips

The tumor microenvironment (TME) plays a critical, yet mechanistically elusive role in tumor development and progression, as well as drug resistance. To better understand the pathophysiology of the complex TME, a reductionist approach has been employed to create in vitro microfluidic models called “tumor chips”. Herein, we review the fabrication processes, applications, and limitations of the tumor chips currently under development for use in cancer research. Tumor chips afford capabilities for real-time observation, precise control of microenvironment factors (e.g. stromal and cellular components), and application of physiologically relevant fluid shear stresses and perturbations. Applications for tumor chips include drug screening and toxicity testing, assessment of drug delivery modalities, and studies of transport and interactions of immune cells and circulating tumor cells with primary tumor sites. The utility of tumor chips is currently limited by the ability to recapitulate the nuances of tumor physiology, including extracellular matrix composition and stiffness, heterogeneity of cellular components, hypoxic gradients, and inclusion of blood cells and the coagulome in the blood microenvironment. Overcoming these challenges and improving the physiological relevance of in vitro tumor models could provide powerful testing platforms in cancer research and decrease the need for animal and clinical studies

Virucidal efficacy comparison of surface disinfection using aerosolized peroxyacetic acid (aPAA), irradiation with UV C-LED or cold plasma

Ziel dieser Studie war es, die viruzide Wirksamkeit von alternativen Desinfektionsverfahren für Oberflächen, ohne den Einsatz von Feucht- und Wischdesinfektion, zu ermitteln. Dabei wurde die Anwendung der Trockenvernebelung aerosolisierter Peroxyessigsäure (aPES), UV C-LED-Strahlung bei 233 und 270 nm sowie einer UV C-Quecksilberlampe bei 254 nm und Kaltplasmastrahlung untersucht. Für diesen Zweck wurden unbelebte Oberflächen wie Edelstahl, Glas und PVC gegenüber einem breiten Erregerspektrum aus behüllten und unbehüllten Viren getestet. Die Auswahl geeigneter Viren erfolgte einerseits anhand der DVV-RKI-Leitlinien, der DVG-Leitlinien und der DIN EN 17272:2020. Andererseits wurden gezielt noch weitere Viren (MS 2 Bakteriophage, Bovines Coronavirus) ausgewählt und hinsichtlich ihrer Eignung als Surrogate untersucht. Zur jeweiligen Anwendung der einzelnen Methoden wurden entsprechende Keimträger aus den unterschiedlichen Materialien eingesetzt, auf denen die virushaltigen Suspensionen angetrocknet wurden. Die anschließende Quantifizierung des Desinfektionserfolges erfolgte durch Abspülen der Keimträger und nachfolgender Titration auf empfänglichen Zellkulturen. Da sowohl der UV C-LED-Strahler mit einer Wellenlänge von 233 nm als auch der Kaltplasmastrahler primär für die Desinfektion von belebten Oberflächen vorgesehen sind, wurde deren zytotoxisches Potenzial sowie die antivirale Wirksamkeit auch auf 2D-Monolayerkulturen und einem etablierten 3D-Schleimhautmodell getestet.The aim of this study was to assess the virucidal efficacy of alternative disinfection methods for surfaces without the use of wet and wipe disinfection. The application of dry fogging of aerosolized peroxyacetic acid (aPAA), UV C-LED radiation at 233 and 270 nm as well as a UV C mercury lamp at 254 nm and cold plasma radiation were investigated. For this purpose, inanimate surfaces such as stainless steel, glass and PVC were tested regarding a broad spectrum of enveloped and non-enveloped viruses. Suitable viruses were selected on the basis of the DVV-RKI guidelines, DVG guidelines and DIN EN 17272:2020 while other viruses (MS 2 bacteriophage, bovine coronavirus) were also specifically choosen and examined with regard to their suitability as surrogates. For the application of the individual methods, corresponding germ carriers made of the different materials were used, on which the virus-containing suspensions were dried. The quantification of the disinfection success was carried out by rinsing the germ carriers and subsequent titration on susceptible cell cultures. Because the UV C-LED radiator with a wavelength of 233 nm and the cold plasma radiator are primarily intended for the disinfection of living surfaces, their cytotoxic potential and virucidal efficacy were also tested on 2D monolayer cultures and an established 3D mucosa model