To study the mechanisms of metastatic disease, we observe tumor cell behavior and migration in collagen-1 bioconjugated LLS™. Laser-scanning confocal microscopy is used to monitor progression, which is further analyzed for tumor margin and identification of motile cells and clusters of cells. Various "paths" can be identified, and in some cases cells are observed augmenting their environment in a way that appears to be supporting further tumor growth and metastasis.

Murine lymph nodes were resected, processed into microtissues, and cultured in collagen-1 bioconjugated LLS™ for 10 days in the 48-well Darcy Microplate™. High levels of viability were observed via imaging with Calcein AM, BOBO-3 Iodide, and Hoechst 33342. Staining for CD45 and CD19 confirmed retention of immune cells generally, and B-cells specifically, on day 10.

Liquid Like Solid (LLS™) microgels are highly tunable including adjustments to surface conjugations of most biopolymers, functional tags, or activation markers, the ability to choose an internal fluorescence, and a range of mechanical characteristics like elastic modulus, hydraulic conductivity, and particle size. In our research, LLS™ properties are chosen to mimic parameters of the niche from which the microtissues are from.

Microtissue models of infectious disease are readily produced as infectious agents such as viruses are easily perfused through LLS™ microgels. Due to size exclusion by the mesh size of the LLS™ hydrogel material, viral particles are ensured to travel through the network of channels and encounter the sample specimens. Lung tissue fragments perfused with SARS-CoV-2 were screened for effective anti-viral drugs.

Real biological systems are inherently cell-dense. Replication of these conditions is only possible in 3D. Aurita has developed protocols for high-density culture on the order of 10 million cells per milliliter for applications in biologic production, viral directed evolution, and expansion of immune cells for cell-based therapy. This is made possible with gentle perfusion in Darcy Plates™ to ensure appropriate waste and metabolite transport.

The missing component of human disease research is an appropriate test track on which to iterate and make discoveries that are directly applicable to real biology. Aurita develops the tools to create that test track. Our team takes an interdisciplinary approach to research and development, with an emphasis on engineering principles, when designing experiments or devices. We are engaged in research with both academic and industrial partners as we refine our 3D culture platform. Contact us at info@auritabio.com to learn more!

Highly local cytokine gradients are strong signals for in the microenvironment that cannot be investigated through sampling of homogenized media supernatants. Concentrations at the periphery of a tissue, a volume of tens of nanoliters, can be orders of magnitude higher than what could be measured by traditional volumetric sampling. Taking advantage of the on/off rates of cytokines to ELISA beads, a 3D dispersion of beads can be interrogated to determine local gradients using laser scanning confocal microscopy.

Aurita has developed methods for reproducible, well characterized, biofabricated micro-tumors and tissues using cell lines, dissociated primary cells, or tissue fragments. Custom fabricated micro-tumors produced with known ratios of cell types and spatial distribution are cultured in BME droplets. Droplet cultures are maintained for extended duration (>10 days) until BME has been fully consumed or remodeled.

The inherent heterogeneity of cancer is a hallmark of the disease that must be accounted for in bench top research models. Aurita cultures micro tumors produced from biopsy material to ensure the inclusion of the entire microenvironment and resident immune populations. Microtumors and tissue samples can grow uninhibited in LLS™ microgels and immune populations are free to explore the network of channels throughout the capillary-mimicking LLS™ bed.