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Biocomputing based on particle disassembly

Abstract

Nanoparticles with biocomputing capabilities could potentially be used to create sophisticated robotic devices with a variety of biomedical applications, including intelligent sensors and theranostic agents. DNA/RNA-based computing techniques have already been developed that can offer a complete set of Boolean logic functions and have been used, for example, to analyse cells and deliver molecular payloads. However, the computing potential of particle-based systems remains relatively unexplored. Here, we show that almost any type of nanoparticle or microparticle can be transformed into autonomous biocomputing structures that are capable of implementing a functionally complete set of Boolean logic gates (YES, NOT, AND and OR) and binding to a target as result of a computation. The logic-gating functionality is incorporated into self-assembled particle/biomolecule interfaces (demonstrated here with proteins) and the logic gating is achieved through input-induced disassembly of the structures. To illustrate the capabilities of the approach, we show that the structures can be used for logic-gated cell targeting and advanced immunoassays.

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Figure 1: Conceptual designs of biocomputing structures for YES/NOT/AND/OR logic basis.
Figure 2: Dependences of output on input concentration for YES gates implemented with different protein-based input-processing interfaces.
Figure 3: YES/NOT gates for CAP in different experimental set-ups.
Figure 4: Double-input gates in the set-up with 3 μm core particles, FH-HRP:STR output receptor's ligand, and quantitative peroxidase assay for output signal readout.
Figure 5: Cell targeting as the output action of logic gating.

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Acknowledgements

The authors thank A.V. Orlov (General Physics Institute, RAS) and P.M. Vetoshko (Institute of Radio Engineering and Electronics, RAS) for assistance with magnetic measurements, A.V. Zherdev and B.B. Dzantiev (Institute of Biochemistry, RAS) for providing the CAP antibody, and I.E. Deyev (Institute of Bioorganic Chemistry, RAS) for supplying GST.

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M.P.N. conceived the idea, designed the study and performed the experiments. V.O.S. assisted with cell targeting experiments. M.P.N., S.M.D. and P.I.N. analysed data and wrote the manuscript.

Corresponding authors

Correspondence to Maxim P. Nikitin or Sergey M. Deyev.

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Competing interests

Two patent applications have been filed by M.P.N. (1) Nikitin, M.P. Logic element complex based on biomolecules (variants). Russian patent no. RU2491631, PCT application WO2013151465 (2012). (2) Nikitin, M.P. Method for determining the content of a ligand in a sample (alternatives). Russian patent no. RU2517161, PCT application WO2013151464 (2012).

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Nikitin, M., Shipunova, V., Deyev, S. et al. Biocomputing based on particle disassembly. Nature Nanotech 9, 716–722 (2014). https://doi.org/10.1038/nnano.2014.156

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