Biological platform for en masse detection of rare cells
Daniel Georgiev, XENO Cell Innovations s.r.o.; Laura Berne , XENO Cell Innovations s.r.o.; Martin Cienciala, XENO Cell Innovations s.r.o.; Tereza Puchrova, XENO Cell Innovations s.r.o.
ZCU TTO, (Transfer and Research, University of West Bohemia)
Due to a fundamental limitation shared by all diagnostic facilities, the majority of information provided by a patient within a standard blood sample is deliberately discarded. The field of modern diagnostics recognizes the importance of patterns. There is a global bioanalytical effort based on machine learning that seeks to unlock patterns in multivariate datasets in order to improve the quality of care. But patterns are a double-edged sword. One on hand, multidimensional data sets are a rich source of information. On the other hand, collecting multidimensional data requires exponentially more effort and resources. Existing experimental tools efficiently measure one-dimensional data but are technologically bottlenecked if the dimension of data points is increased to two. Protein concentrations are routinely measured through ELISA in 1536 batches. Measurement of heterogeneous particles (i.e., particles defined by two or more markers), however, requires brute force flow cytometry. ELISA is a purely biological solution employing parallelization, flow cytometry is a purely electromechanical solution requiring serialism. The challenge is to extend biological parallelization to simplify the detection of heterogeneous targets (e.g., viral particles, exosomes, microbial cells, mammalian cells). Such technologies stand to have an impact across the medical spectrum.
Our team has developed a biological platform for modular detection of surface marker profiles on cellular targets, specifically targets suspended in complex samples. The technology is particularly applicable to detection of rare circulating tumour cells or immune cells collected in samples of peripheral blood. The overall function is comparable to flow cytometry in that a set of positive and negative gates are evaluated on each potential target cell. The function is unique in that the entire gating process is purely biological and occurs within the bulk sample volume. Target cells are never extracted from the sample by enrichment or otherwise. The solution comprises a microbial cocktail of genetically engineered yeast strains. This cocktail is mixed with a standard blood sample and incubated for a fixed time. Subsequently, results are given via a simple colorimetric readout, e.g., in a standard plate reader. To the user, the assay is comparable in effort to ELISA.
The primary impact is expected in the liquid biopsy space. Over $10B has been raised by newly founded companies, e.g., Grail ($1.6B), Freenome ($238M), Foundation Medicine ($2.4B), Guardant ($550M), to revolutionize cancer diagnostics with blood tests enabling early detection, treatment monitoring, and relapse screening. Technologically, however, this space is extremely narrow with liquid biopsy essentially reduced to NGS enabled genetic liquid biopsy. The XENO platform has a high potential for improving the specificity of liquid biopsy and for bridging the gap between liquid biopsy and the clinical de facto standard, the solid biopsy.
The technological IP is fully owned by XENO Cell Innovations s.r.o. founded in 2016. The latest technological development is in agreement with TRL 5 as defined by the European Commission, i.e., the technology is validated in a laboratory setting on defined samples comprising a complex matrix spiked with immortalized cell lines.
The above-described technology is protected by a Patent Cooperation Treaty (PCT) international application filed on September 6, 2019, designating all PCT member states and regions.