Format chain exchange (FORCE) for high-throughput generation of bispecific antibodies in combinatorial binder-format matrices

Generation of bispecific antibodies (bsAbs) requires a combination of compatible binders in formats that support desired functionalities. Here, we report that bsAb-matrices can be generated by Format Chain Exchange (FORCE), enabling screening of combinatorial binder/format spaces. Input molecules for generation of bi/multi-valent bsAbs are monospecific entities similar to knob-into-hole half-antibodies, yet with complementary CH3-interface-modulated and affinity-tagged dummy-chains. These contain mutations that lead to limited interface repulsions without compromising expression or biophysical properties of educts. Mild reduction of combinations of educts triggers spontaneous chain-exchange reactions driven by partially flawed CH3-educt interfaces resolving to perfect complementarity. This generates large bsAb matrices harboring different binders in multiple formats. Benign biophysical properties and good expression yields of educts, combined with simplicity of purification enables process automation. Examples that demonstrate the relevance of screening binder/format combinations are provided as a matrix of bsAbs that simultaneously bind Her1/Her2 and DR5 without encountering binder or format-inflicted interferences.

Quantum statistics

Indistinguishability of like particles, and the fermion and boson exchange symmetries discussed.Pauli exclusion principle and features of multi-electron atoms, including selection rules are discussed. Degeneracy pressure and the formation of compact stellar objects is analysed. Quantum exchange force between electrons and its contribution to ferromagnetism is outlined. Fermi-Dirac and Bose-Einstein statistics, includng the chemical potential are derived. The conditions for Bose-Einstein condensation are deduced; condensates and their stability are considered.

Magnetic exchange force microscopy: theoretical analysis of induced magnetization reversals

In magnetic exchange force microscopy a magnetic tip is scanned over the surface of a solid and an image representing the exchange interaction recorded. Theoretical calculations are presented showing how lifetime of the magnetic states depends on tip size, distance and magnetic field.

Observation of Ferromagnetic Resonance in Magnetic Exchange Force Microscopy (MExFM)

The atomic spin interaction is very important for understanding the superficially magnetic feature of nanostructure at atomic level. Magnetic exchange force microscopy (MExFM) is an innovative means of measuring surface spin force. But it is difficult to separate the surface topography and spin information. We develop the magnetic exchange force microscopy using ferromagnetic resonance (FMR-MExFM). The theoretical and experimental results demonstrate that this method can separate the two kinds of information effectively. Here, in order to obtain the high sensitivity in detecting the ferromagnetic resonance, we fabricate the microwave irradiation device to optimize the position between the device and the cantilever. We have succeeded in observing the ferromagnetic resonance effect and determining its resonant frequency using the homemade microwave irradiation device and the network analyzer. This research is very important for developing FMR-MExFM and novel magnetic sensor, detecting the magnetic information, etc.