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Abstract Objective Our aim was to produce a mono-biotinylated single domain antibody (‘nanobody’) specific for the epidermal growth factor receptor (EGFR), which is overexpressed in many cancer cells. The binding of the nanobody and its function are tested in cancer cells. The construct could be used to carry variable therapeutic or diagnostic load using biotin-streptavidin bridging. Results The EGFR-specific 7D12 nanobody was genetically fused to an IgA hinge linker and to a C-terminal biotin ligase acceptor sequence, allowing mono-biotinylation in E. coli. Expression was in strain BL21-DE3 from a T7 RNA polymerase driven pET22b vector. The biotinylated nanobody, isolated from the periplasm, was purified using streptavidin-mutein affinity chromatography. Final yields were up to 5 mg/l of cell culture. We showed that the construct could bind to EGFR expressing A431 epidermoid carcinoma cells, and to transiently transformed EGFR overexpressing HEK293T cells and not to EGFR negative control cells. The specificity for the EGFR was further demonstrated by immunoprecipitation. To test the functionality, PC9 non-small cell lung cancer cells were treated with mono-biotinylated nanobody or with streptavidin-coupled tetravalent nanobodies. Both were able to block mutant EGFR phosphorylation and slow down growth of PC9 cells. Tetravalent nanobodies were able to downregulate AKT phosphorylation.

Objective collapse theories propose a solution to the quantum measurement problem by predicting deviations from Schrödinger's equation that can be tested experimentally. A class of objective theories based on spontaneous unitarity violation was recently introduced, in which the stochastic field required for obtaining Born's rule does not depend on the state of the system being measured. Here, we classify possible models for the stochastic field dynamics in theories of spontaneous unitarity violation. We show that for correlated stochastic dynamics, the field must be defined on a closed manifold. In two or more dimensions, it is then always possible to find stochastic dynamics yielding Born's rule, independent of the state being measured or the correlation time of the stochastic field. We show that the models defined this way are all isomorphic to the definition on a two-sphere, which we propose to be a minimal physical model for the stochastic field in models of spontaneous unitarity violation.

The impossibility of describing measurement in quantum mechanics while using a quantum mechanical model for the measurement machine, remains one of its central problems. Objective collapse theories attempt to resolve this problem by proposing alterations to Schrödinger's equation. Here, we present a minimal model for an objective collapse theory that, in contrast to previous proposals, does not employ state dependent stochastic terms in its construction. It is an explicit proof of principle that it is possible for Born's rule to emerge from a stochastic evolution in which no properties of the stochastic process depend on the state being evolved. We propose the presented model as a basis from which more realistic objective collapse theories can be constructed.