Monolayer culture systems are used by pharmaceuticals and research labs to investigate the efficacy

Biocompatibility is an essential aspect of the medical device industry. Biocompatibility testing ensures that devices do not contain materials or substances that could be harmful to patients during initial use or over the course of time. Biocompatibility tests can be used to detect many possible negative side effects of a product on patient. These may include effects on cells and physiological systems, tissue irritation and inflammation, immunological and allergic reactions and the possibility of cellular mutations leading to cancer. Email:marketing@medicilon.com.cn web:www.medicilon.com

Microfabricated platforms can be used to study a heterogeneous panel of biosamples in a realistic in vivo setting. The platform can be formed of a polymer and can be constructed for implantation into an animal host for in vivo testing. The platform can have a plurality of testing regions therein that are constructed to allow exposure of the testing region to the host stroma when implanted in vivo. For example, the microfabricated platform can be used for screening different cancer cell-lines or for screening different biomaterials .

The present application relates generally to testing of biological samples, and, more particularly, to systems, methods, and devices for multiplexed in vivo screening of biological samples, for example, for cancer drug screening or material biocompatibility testing.

Monolayer culture systems are used by pharmaceuticals and research labs to investigate the efficacy of anti-cancer therapeutic agents. However, the inability of the monolayer system to mimic tumor microenvironment leads to inaccurate prediction of drug efficacy in vivo. Often, promising lead compounds fail in the later phases of clinical trials despite initially encouraging results. Compared to other therapeutic areas, there is a particularly high attrition rate for anti-cancer drugs. Indeed, in recent years there have been a large number of unsuccessful clinical trials, with only 8% of drug candidates which enter Phase I trials actually reaching the bedside.

Individual anti-cancer compounds may only be effective for cells with specific genotypes. Efficacy studies to determine which genotypes a particular drug is effective against are performed at a relatively low throughput in animal models. A single compound is thus screened against one genotype per animal. While animal models, such as transgenic mice and xenograft models, can serve as a promising tool for preclinical studies, the low throughput of these systems and the inability to test large number of cell-lines limits their potential to capture the genomic heterogeneity of cancer. It is therefore logistically challenging to identify the subgroups of responsive cancer cells for the developed rationally targeted drugs.

An effective high-throughput method to identify in vivo (not just in vitro) efficacious compounds, as well as identifying the cell types that would be susceptible to compounds and/or other treatment therapies or devices, well before the expensive Phase II/III clinical trials could make the drug discovery process much more cost-effective. In addition, biomaterials can be used in various in vivo applications, such as drug delivery devices, artificial heart valves, intraocular lenses, scaffolds for cell transplantations, coatings for medical implants, etc. The success of these applications relies at least in part on the response of the host to the implanted biomaterial. The testing of host response can be performed by implanting a material of a single composition into a single host. In order to test the biocompatibility of many compositions and/or materials, many animals would be necessary. Not only would a large number of animals need to be sacrificed during such testing, but variance in observed responses due to inconsistencies in host microenvironment and in surgical operation may increase. High throughput testing of in vivo host response of biomaterials may serve to reduce the number of animals needed as well as improve testing results and consistency.

Microfabricated platforms can be used to study a heterogeneous panel of biosamples in a realistic in vivo setting. The platform can be formed of a polymer and can be constructed for implantation into an animal host for in vivo testing. The platform can have a plurality of testing regions therein that are constructed to allow exposure of the testing region to the host stroma when implanted in vivo. For example, the microfabricated platform can be used for screening different cancer cell-lines or for screening different biomaterials. For example, hydrogel precursors and cells may be 3D-printed to form a structure that immobilizes the cells. Alternatively, cells may be sandwiched between preformed hydrogel plates. Still other means for fabricating three-dimensional or two-dimensional structures can be employed. Any structure suitable for immobilizing and isolating cells of differing genotype from each other while permitting the transmission of mechanical, chemical, thermal, or other signals from stromal cells may be employed.

In one or more embodiments, the testing regions may be individual chambers holding respective tumor spheroids therein. A membrane layer may retain the tumor spheroid within the interior of each chamber while allowing stromal cell interaction with the tumor spheroid. The tumors may be of different genotypes from each other so as to allow simultaneous testing of multiple genotypes in a single host animal. An anti-cancer drug (or any other type of therapeutic device or agent) can be given to the host animal while (or before) the platform is implanted therein, thereby subjecting each of the tumor genotypes to the same host environment at the same time. The construction and arrangement of the platform and the testing regions may be such that the cross-talk between adjacent testing regions is minimized or at least reduced.