Publications by authors named "Sarah Spitz"

Label-free imaging through two-photon autofluorescence of NAD(P)H allows for nondestructive, high-resolution visualization of cellular activities in living systems. However, its application to thick tissues has been restricted by its limited penetration depth within 300 μm, largely due to light scattering. Here, we demonstrate that the imaging depth for NAD(P)H can be extended to more than 700 μm in living engineered human multicellular microtissues by adopting multimode fiber-based, low repetition rate, high peak power, three-photon excitation of NAD(P)H at 1100 nm.

View Article and Find Full Text PDF

The blood-brain barrier (BBB) serves as a selective filter that prevents harmful substances from entering the healthy brain. Dysfunction of this barrier is implicated in several neurological diseases. In the context of Alzheimer's disease (AD), BBB breakdown plays a significant role in both the initiation and progression of the disease.

View Article and Find Full Text PDF

Neurodegenerative diseases (NDDs) affect more than 50 million people worldwide, posing a significant global health challenge as well as a high socioeconomic burden. With aging constituting one of the main risk factors for some NDDs such as Alzheimer's disease (AD) and Parkinson's disease (PD), this societal toll is expected to rise considering the predicted increase in the aging population as well as the limited progress in the development of effective therapeutics. To address the high failure rates in clinical trials, legislative changes permitting the use of alternatives to traditional pre-clinical in vivo models are implemented.

View Article and Find Full Text PDF

Affecting millions of individuals worldwide, neurodegenerative diseases (NDDs) pose a significant and growing health concern in people over the age of 60 years. Contributing to this trend are the steady increase in the aging population coupled with a persistent lack of disease-altering treatment strategies targeting NDDs. The absence of efficient therapeutics can be attributed to high failure rates in clinical trials and the ineptness of animal models in preceding preclinical studies.

View Article and Find Full Text PDF

Neutral and positively charged archaeal ether lipids (AEL) have been studied for their utilization as novel delivery systems for pDNA, showing efficient immune response with a strong memory effect while lacking noticeable toxicity. Recent technological advances placed mRNA lipid nanoparticles (LNPs) at the forefront of next-generation delivery systems; however, no study has examined AELs in mRNA delivery yet. In this study, we investigated either a crude lipid extract or the purified tetraether lipid caldarchaeol from Sulfolobus acidocaldarius as potential novel excipients for mRNA LNPs.

View Article and Find Full Text PDF
Article Synopsis
  • Neutralizing antibodies against SARS-CoV-2, acquired from prior infections or vaccinations, are critical in preventing COVID-19 outbreaks unless the virus changes.
  • The study introduces a novel lateral flow assay (LFA) that uses a biomimetic mock virus system with functionalized gold nanoparticles to detect these antibodies in blood samples.
  • The assay features enhanced sensitivity for identifying low antibody levels and has been validated against WHO standards, making it reliable for point-of-care testing.
View Article and Find Full Text PDF

High failure rates in clinical trials for neurodegenerative disorders such as Alzheimer's disease have been linked to an insufficient predictive validity of current animal-based disease models. This has created an increasing demand for alternative, human-based models capable of emulating key pathological phenotypes . Here, a three-dimensional Alzheimer's disease model was developed using a compartmentalized microfluidic device that combines a self-assembled microvascular network of the human blood-brain barrier with neurospheres derived from Alzheimer's disease-specific neural progenitor cells.

View Article and Find Full Text PDF

Glucose is the primary energy source of human cells. Therefore, monitoring glucose inside microphysiological systems (MPS) provides valuable information on the viability and metabolic state of the cultured cells. However, continuous glucose monitoring inside MPS is challenging due to a lack of suitable miniaturized sensors.

View Article and Find Full Text PDF
Article Synopsis
  • The human brain lacks a traditional lymphatic system, leading researchers to explore alternative ways to clear waste, resulting in the discovery of the glymphatic system which connects cerebrospinal fluid to lymphatic vessels.
  • The glymphatic system helps transport solutes and clear waste in the brain, playing a critical role in neurodegenerative diseases, but much of the current understanding comes from animal studies, which have limitations.
  • Advances in organ-on-a-chip technology offer new human-based in vitro research models to better understand the glymphatic system and explore potential treatments for neurodegenerative disorders.
View Article and Find Full Text PDF

The re-creation of physiological cellular microenvironments that truly resemble complex architectures is the key aspect in the development of advanced organotypic tissue constructs. Among others, organ-on-a-chip technology has been increasingly used in recent years to create improved models for organs and tissues in human health and disease, because of its ability to provide spatio-temporal control over soluble cues, biophysical signals and biomechanical forces necessary to maintain proper organotypic functions. While media supply and waste removal are controlled by microfluidic channel by a network the formation of tissue-like architectures in designated micro-structured hydrogel compartments is commonly achieved by cellular self-assembly and intrinsic biological reorganization mechanisms.

View Article and Find Full Text PDF

Stem cell technology and embryonic stem cell models are of great interest in biomedical research since they provide deeper insights into, e.g., neurogenesis and early mammalian brain development.

View Article and Find Full Text PDF

Translation of advanced cell-based assays exhibiting a higher degree of automation, miniaturization, and integration of complementary sensing functions is mainly limited by the development of industrial-relevant prototypes that can be readily produced in larger volumes. Despite the increasing number of academic publications in recent years, the manufacturability of these microfluidic cell cultures systems is largely ignored, thus severely restricting their implementation in routine toxicological applications. We have developed a dual-sensor integrated microfluidic cell analysis platform using industrial specifications, materials, and fabrication methods to conduct risk assessment studies of engineered nanoparticles to overcome this academic-industrial gap.

View Article and Find Full Text PDF

Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane as the joint capsule's inner layer is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bone erosion and cartilage destruction. While microfluidic models that model molecular aspects of bone erosion between bone-derived cells and synoviocytes have been established, RA's synovial-chondral axis has not yet been realised using a microfluidic 3D model based on human patient cultures.

View Article and Find Full Text PDF

Owing to their self-renewal and multi-lineage differentiation capability, mesenchymal stem cells (MSCs) hold enormous potential in regenerative medicine. A prerequisite for a successful MSC therapy is the rigorous investigation of their function after in vitro cultivation. Damages introduced to mitochondria during cultivation adversely affect MSCs function and can determine their fate.

View Article and Find Full Text PDF

The understanding that systemic context and tissue crosstalk are essential keys for bridging the gap between in vitro models and in vivo conditions led to a growing effort in the last decade to develop advanced multi-organ-on-a-chip devices. However, many of the proposed devices have failed to implement the means to allow for conditions tailored to each organ individually, a crucial aspect in cell functionality. Here, we present two 3D-print-based fabrication methods for a generic multi-organ-on-a-chip device: One with a PDMS microfluidic core unit and one based on 3D-printed units.

View Article and Find Full Text PDF

Organ-on-a-chip technology has the potential to accelerate pharmaceutical drug development, improve the clinical translation of basic research, and provide personalized intervention strategies. In the last decade, big pharma has engaged in many academic research cooperations to develop organ-on-a-chip systems for future drug discoveries. Although most organ-on-a-chip systems present proof-of-concept studies, miniaturized organ systems still need to demonstrate translational relevance and predictive power in clinical and pharmaceutical settings.

View Article and Find Full Text PDF

In this study, we have aimed at developing a novel electrochemical sensing approach capable of detecting dopamine, the main biomarker in Parkinson's disease, within the highly complex cell culture matrix of human midbrain organoids in a non-invasive and label-free manner. With its ability to generate organotypic structures in vitro, induced pluripotent stem cell technology has provided the basis for the development of advanced patient-derived disease models. These include models of the human midbrain, the affected region in the neurodegenerative disorder Parkinson's disease.

View Article and Find Full Text PDF

Biomechanical cues such as shear stress, stretching, compression, and matrix elasticity are vital in the establishment of next generation physiological tissue models. Matrix elasticity, for instance, is known to guide stem cell differentiation, influence healing processes and modulate extracellular matrix (ECM) deposition needed for tissue development and maintenance. To better understand the biomechanical effect of matrix elasticity on the formation of articular cartilage analogs , this study aims at assessing the redifferentiation capacity of primary human chondrocytes in three different hydrogel matrices of predefined matrix elasticities.

View Article and Find Full Text PDF

Glucose transport is key for cellular metabolism as well as physiological function and is maintained via passive facilitated and active sodium-glucose linked transport routes. Here, we present for the first time Fourier-transform infrared spectroscopy as a novel approach for quantification of apical-to-basolateral glucose transport of in vitro cell barrier models using liver, lung, intestinal and placental cancer cell lines. Results of our comparative study revealed that distinct differences could be observed upon subjection to transport inhibitors.

View Article and Find Full Text PDF

Synthetic biology aims to understand fundamental biological processes in more detail than possible for actual living cells. Synthetic biology can combat decomposition and build-up of artificial experimental models under precisely controlled and defined environmental and biochemical conditions. Microfluidic systems can provide the tools to improve and refine existing synthetic systems because they allow control and manipulation of liquids on a micro- and nanoscale.

View Article and Find Full Text PDF

Knowledge on the availability of dissolved oxygen inside microfluidic cell culture systems is vital for recreating physiological-relevant microenvironments and for providing reliable and reproducible measurement conditions. It is important to highlight that cells experience a diverse range of oxygen tensions depending on the resident tissue type, which can also be recreated using specialized cell culture instruments that regulate external oxygen concentrations. While cell-culture conditions can be readily adjusted using state-of-the-art incubators, the control of physiological-relevant microenvironments within the microfluidic chip, however, requires the integration of oxygen sensors.

View Article and Find Full Text PDF

Reengineering functional vascular networks remains an integral part in tissue engineering, since the incorporation of non-perfused tissues results in restricted nutrient supply and limited waste removal. Microfluidic devices are routinely used to mimic both physiological and pathological vascular microenvironments. Current procedures either involve the investigation of growth factor gradients and interstitial flow on endothelial cell sprouting alone or on the heterotypic cell-cell interactions between endothelial and mural cells.

View Article and Find Full Text PDF

It is crucial but challenging to keep physiologic conditions during the cultivation of 3D cell scaffold constructs for the optimization of 3D cell culture processes. Therefore, we demonstrate the benefits of a recently developed miniaturized perfusion bioreactor together with a specialized incubator system that allows for the cultivation of multiple samples while screening different conditions. Hence, a decellularized bone matrix was tested towards its suitability for 3D osteogenic differentiation under flow perfusion conditions.

View Article and Find Full Text PDF