A.G. Gudkov - Dr.Sc. (Eng.), Professor, Department of Instrumentation Technology, MSTU n.a. N.E. Bauman; General Director, OOO «NPI FIRMA «HYPERION» (Moscow). E-mail: profgudkov@gmail.com; ooo.giperion@gmail.com V.V. Zherdeva - Ph.D. (Biol.), Associate Professor, GBOU DPO RMAPO MZ RF (Moscow). E-mail: zherdeva.victoria@gmail.com V.N. Viyuginov - Ph.D. (Phys.-Math.), Director, CJSC «Svetlana-Elektronpribor» (St. Peterburg). E-mail: vyuginov@svetlana-ep.ru A.A. Zybin - Head of Laboratory, CJSC «Svetlana-Elektronpribor» (St. Peterburg). E-mail: zybin_aa@svetlana-ep.ru V.G. Tihomirov - Ph.D. (Phys.-Math.), CJSC «Svetlana-Elektronpribor» (St. Peterburg). E-mail: v11111@yandex.ru A.S. Borzinets - Technican, MSTU n.a. N.E. Bauman. E-mail: baosi@mail.ru

This article provides an overview the different directions of biosensor diagnostics. This artical shows the classification biosensors on the following criteria: application (for use in vitro / in vivo), the transmission mechanism of the biological signal, which is based interaction can be based antigen-antibody, substrate-enzyme, complementary DNA interaction sites metabolism of living cells use biosensorov- biomimics etc., a method of signal conversion (optical, electrochemical, mass-sensing, thermal). Various principles of invasive implantable biosensors based on the principle of cyclic voltmeter is completed. Some interesting approaches for the protection the surface of biosensor, the biosensor according to the power supply, which can be used with other electrical biosensor detection, including those based on field-effect transistors are designed. However, these biosensors have a small lifetime and low sensitivity. The principles of the development of biosensors based on AlGaN / GaN HEMT-transistors, different methods of immobilization of sensor molecules on the gate region, principally shown their stability, biocompatibility, the ability to achieve ultra-high sensitivities for such biosensors. It is shown that the possibility of widespread use of biosensors in vivo is limited to a set of requirements to them. First of all, it is non-invasive (or minimally invasive) in order to avoid changes in the properties of a biological object, which is achieved by the minia-turization of the biosensor from micro- to nano-scale; equally important requirement is the low toxicity of the materials of which the biosensor. The feasibility of using the biosensor in vivo is determined by the tasks of monitoring of certain biochemical processes in the body with high sensitivity when other methods can not give a complete, detailed picture of the time. You must be able to manage a biosensor, or remote contact method. Definitely preference should be given to biosensors that meet the above requirements and combine different modalities: eg, diagnosis and treatment (theranostics) or detection of several processes at the same time (multi-modal).

 

1. Nanostruktury v biomedicine / pod red. K.E. Gonsalves, K.R. KHalbershtadt, K.T. Lorensin, L.S. Nair / per. s angl. M.: Binom. Laboratorija znanijj. 2012. 519 s.
2. Varfolomeev S.D., Evdokimov JU.M., Ostrovskijj M.A. Sensornaja biologija, sensornye tekhnologii i sozdanie novykh organov chuvstv cheloveka // Vestnik Rossijjskojj akademii nauk. 2000. № 2(70). S. 99-108.
3. Gudkov A.G., Vjuginov V.N., Zybin A.A., Meshkov S.A., Cyganov D.I. Issledovanie putejj konstruktorsko-tekhnologicheskojj realizacii invazivnykh biosensorov na osnove HEMT-tranzistorov // Tekhnika mashinostroenija. 2014. № 2(90). S. 57-60.
4. Vjuginov V.N., Gudkov A.G., Zybin A.A., Meshkov S.A., Cyganov D.I. Vybor skhemotekhnicheskikh, konstruktorskikh i tekhnologicheskikh reshenijj pri razrabotke invazivnogo tranzistornogo biosensora // EHlektromagnitnye volny i ehlektronnye sistemy. 2014. T. 22. № 4. S. 66-70.
5. Ivanov JU.A., Gudkov A.G., Meshkov S.A., SHashurin V.D., Klevcov V.A., Agasieva S.V., Sinjakin V.JU. Primenenie rezonansno-tunnelnykh nanodiodov dlja povyshenija ehffektivnosti preobrazovatelja ehlektromagnitnojj ehnergii invazivnykh biosensornykh sistem na baze tekhnologii radiochastotnojj identifikacii // EHlektromagnitnye volny i ehlektronnye sistemy. 2014. T. 22. № 4. S. 60-65.
6. Ivanov JU.A., Agasieva S.V., Gudkov A.G., Meshkov S.A., Sinjakin V.JU., SHashurin V.D. Primenenie tekhnologii radiochastotnojj identifikacii s passivnymi metkami v invazivnojj biosensorike // Mashinostroitel. 2014. № 5. S. 12-20.
7. Wang W.DuY., Luo Q., LiuB.-F. Optical molecular imaging for systems biology: from molecule to organism // Anal. Bioanal. Chem. 2006. V. 386. P. 444-457.
8. Savickijj V.V. ZHerdeva I.G. Meerovich. Primenenie fluorescentnogo imidzhinga na osnove reporternykh genov cvetnykh fluorescentnykh belkov v izuchenii molekuljarnykh mekhanizmov fotodinamicheskojj terapii // Fundamentalnye nauki medicine: Biofizicheskie medicinskie tekhnologii: Monografija: v 2-kh tomakh. T.1 / pod red. A.I. Grigoreva i JU.A. Vladimirova. M.: MAKS Press. 2015. Gl. 2. S. 265-313.
9. Leung K., Chopra A., Shan L., Eckelman W.C, Menkens A.E. Essential parameters to consider for the characterization of optical imaging probes. Nanomedicine (Lond). 2012. № 7(7). P. 1101-1107. doi: 10.2217/nnm.12.79.
10. Leblond F., Davis S.C., Valdés P.A., Pogue B.W.Preclinical Whole-body Fluorescence Imaging: Review of Instruments, Methods and Applications // J. Photochem. Photobiol. B. 2010. № 98(1). P. 77-94. doi:10.1016/j.jphotobiol.2009.11.007.
11. Weissleder R., Tung C.H., Mahmood U., Bogdanov A.(Jr.)In vivo imaging of tumors with protease activated near-infrared fluo­rescent probes // Nat Biotechnol. 1999. V. 17. P. 375-378.
12. Ntziachristos V., Bremer C., Graves E.E., Ripoll J., Weissleder R. In vivo tomographic imaging of nearinfrared fluorescent probes // Mol. Imaging.2002. № 1. P. 82-88.
13. Resch-Genger, U., et al. Quantum dots versus organic dyes as fluorescent labels // Nat. Methods. 2008. № 5(9). P. 763-775.
14. Gao X., et al. In vivo cancer targeting and imaging with semiconductor quantum dots // Nat. Biotechnol. 2004. № 22(8). P. 969-976.
15. Karabanovas V., Zakarevicius E., Sukackaite A., Streckyte G., Rotomskis R. Examination of the stability of hydrophobic (CdSe)ZnS quantum dots in the digestive tract of rats // Photochem. Photobiol. Sci. 2008. V. 7. P. 725-728.
16. Loginova JA.F., ZHerdeva V.V., Kazachkina N.I., Savickijj A.P. Bioraspredelenie i farmakokinetika kvantovykh tochek pri raznykh sposobakh vvedenija // Sbornik statejj Vtorojj Mezhdunar. nauchno-praktich. konf. «Vysokie tekhnologii, fundamentalnye i prikladnye issledovanija v fiziologii i medicine» / pod red. A.P. Kudinova i B.V. Krylova. SPb.: Izd-vo Politekhn. un-ta. 2011. T. 2. C. 217-219.
17. He X., Ma N. An overview of recent advances in quantum dots for biomedical applications // Colloids and Surfaces B. 2014. V. 124. P. 118-131.
18. Zhou J., Liub Zh., Li F. Upconversion nanophosphors for small-animal imaging // Chem. Soc. Rev. 2012. V. 41. P. 1323-1349.
19. Nyk M., Kumar R., Ohulchanskyy T., et al. // Nano Lett. 2008. № 8. R. 3834-3838.
20. Fischer H.C., Liu L., Pang K.S., Chan W.C.W.Pharmacokinetics of Nanoscale Quantum Dots: In vivo distribution, sequestration, and clearance in the rat // Advanced Functional Materials. 2006. № 16. R. 1299-1305.
21. Schipper M.L., Iyer G., Koh A.L., Cheng Z., Ebenstein Y., Aharoni A., Keren S., Bentolila L.A., Li J., Rao J., Chen X., Banin U., Wu A.M., Sinclair R., Weiss S., Gambhir S.S. Particle size, surface coating, and PEGylation influence the biodistribution of quantum dots in living mice // Small. 2009. № 5.
22. Janát-Amsbury A.M.M., Ray A., Peterson C.M., GhandehariH. Geometry and Surface Characteristics of Gold Nanoparticles Influence their Biodistribution and Uptake by Macrophages // Eur. J. Pharm. Biopharm. 2011. V. 77. № 3. R. 417-423.
23. Cao T., Yang Y., Sun Y., Wu Y., Gao Y., Feng W., Li F.Biodistribution of sub-10nm PEG-modified radioactive /upconversion nanoparticles // Biomaterials. 2013. V. 34. № 29. R. 7127-1734. doi: 10.1016/j.biomaterials.2013.05.028. Epub 2013 Jun 21.
24. Grebenik E.A., Nadort A., Generalova A.N., Nechaev A.V., Sreenivasan V.K.A., Khaydukov E.V., Semchishen V.A., Popov A.P., Sokolov V.I., Akhmanov A.S., Zubov V.P., Klinov D.V., Panchenko V.Y., Deyev S.M., Zvyagin A.V. Feasibility study of the optical imaging of a breast cancer lesion labeled with upconversion nanoparticle biocomplexes // J. Biomed. Opt. 2013. V. 18. № 7.  R. 076004. doi:10.1117/1.JBO.18.7.076004.
25. Key J., James F. Nanoparticles for multimodal in vivoimaging in nanomedicine // International Journal of Nanomedicine. 2014. № 9. R. 711-726
26. Choy G.,Choyke P.,Libutti S.K.Current advances in molecular imaging: noninvasive in vivo bioluminescent and fluorescent optical imaging in cancer research // Mol. Imaging.2003. V. 2. № 4. R. 303-312.
27. Joo Hyun Kang, June-Key Chungl. Molecular-Genetic Imaging Based on ReporterGene Expression // J. Nucl. Med. 2008. № 49. R. 164S-179S
28. Zherdeva V.V., Savitsky A.P. Using Lanthanide_Based Resonance Energy Transfer for in vitro and in vivo Studies of Biological Processes // Biochemistry. 2012. V. 77. № 13. R. 1553.
29. Rajapakse H.E.,Reddy D.R.,Mohandessi S.,Butlin N.G.,Miller L.W. Luminescent terbium protein labels for time-resolved microscopy and screening // Angew. Chem. Int. Ed. Engl. 2009. V. 48. Is. 27. R. 4990-4992.
30. Hoffman R.M. The multiple uses of fluorescent proteins to visualize cancer in vivo // Nat. Rev. Cancer. 2005. № 5. R. 796-806.
31. Chudakov D.M., Matz M.V., Lukyanov S., Lukyanov K.A. Fluorescent proteins and their applications in imaging living cells and tissues // Physiol. Rev. 2010. V. 90. № 3. R. 1103-1163. doi:10.1152/physrev.00038.2009.
32. Rusanov A.L., Savitsky A.P. Fluorescence resonance energy transfer between fluorescent proteins as powerful toolkits for in vivo studies // Laser Phys. Lett. 2011. V. 8. № 2. R. 91-102. doi:10.1002/lapl.201010107.
33. Savitsky A.P., Rusanov A.L., Zherdeva V.V., Gorodnicheva T.V., Khrenova M.G., Nemukhin A.V. FLIM-FRET Imaging of caspase-3 activity in live cells using pair of red fluorescent proteins // Theranostics. 2012. V. 2. № 2. R. 215-226. doi:10.7150/thno.3885.
34. Ambacher O., Eickhoff M., Steinhoff G., Hermann M., Gorgens L., Werss V. // Proc. ECS. 2002. № 27. R. 214.
35. Neuberger R., Muller G., Ambacher O., Stutzmann M. // Phys. Status Solidi A. 2001. № 185. R. 85.
36. Schalwig J., Muller G., Ambacher O., Stutzmann M. // Phys Status Solidi A. 2001. № 185. R. 39.
37. Steinhoff G., Hermann M., Schaff W.J., Eastman L.F., Stutzmann M., Eickhoff M. // Appl. Phys. Lett. 2003. № 83. R. 177.
38. Eickhoff M., Neuberger R., Steinhoff G., Ambacher O., Muller G., Stutzmann M. Phys. Status Solidi B. 2001. № 228. R. 519.
39. Schalwig J., Muller G., Eickhoff M., Ambacher O., Statzmann M. // Sens. Actuat. B. 2002. № 81. R. 425.
40. Stutzmann M., Steinhoff G., Eickhoff M., Ambacher O., Nobel C.E., Schalwig J., et al. Diamond Rel. Mater. 2002. № 11. R. 886.
41. Kang B.S., Wang H.T., Ren F., Pearton S.J. Electrical detection of biomaterials using AlGaN/GaN HEMTs // J. Appl. Phys. 2008. V. 104. № 8. R. 031101
42. Tikhomirov V.G., Maleev N.A., Kuzmenkov A.G., Solovev JU.V., Gladyshev A.G., Kulagina M.M., Zemljakov V.E., Dudinov K.V., JAnkevich V.B., Bobyl A.V., Ustinov V.M. // FTP. 2011. V. 45. № 10. R. 1405.
43. Vyuginov V.N., Gudkov A.G., Dobrov V.A., Leushin V.Yu., Meshkov S.A., Popov V.V. Account of inheritable characteristics interns of complex technological optimization of MMIC // 2011 21th Int. Crimean Conf. «Microwave & Telecommunication Yechnology» (CriMiCo-2011). Sevastopol. 2011. 709 r.