Синтез микро- и наночастиц в микрофлюидных реакторах для биомедициского применения

В настоящее время наблюдается тенденция к внедрению микрофлюидных устройств во многих областях биомедицины: синтез лекарств, тераностика, биосенсоры. Такие устройства обеспечивают быстрое и достаточное перемешивание в микрофлюидных каналах, позволяют получать монодисперсные частицы, в том числе наноразмерные, проводить контроль за условиями синтеза и точно регулировать физико-химические свойства получаемых субстанций. Сенсоры на основе микрофлюидики позволяют детектировать различные патологические процессы. Настоящий обзор литературы дает представление о принципах построения микрофлюидных устройств и систем дозирования реактивов, а также о материалах для микрофлюидных чипов. Приведены примеры использования микрофлюидики в различных областях биомедицины.

1. El-Housiny S, Eldeen M A S, El-Attar YA, et al. Fluconazole-loaded solid lipid nanoparticles topical gel for treatment of pityriasis versicolor: formulation and clinical study. Drug Deliv. 2018;25(1):78-90.

2. Millstone JE, Kavulak DFJ, Woo CH, et al. Synthesis, properties, and electronic applications of size-controlledpoly(3-hexylthiophene) nanoparticles. Langmuir. 2010;26:13056–13061.

3. Arroyo GV, Madrid AT, Gavilanes AF, et al. Green synthesis of silver nanoparticles for application in cosmetics. Journal of environmental science and health, part A. 2020;55(11):1304-1320.

4. Gao Y, Wu Y, Lu H, et al. CsPbBr3 perovskite nanoparticles as additive for environmentally stable perovskite solar cells with 20.46% efficiency. Nano Energy. 2019;63:103838.

5. Lin CH, Lee GB, Lin YH, et al. A Fast Prototyping Process for Fabrication of Microfluidic Systems on Soda-Lime Glass. J. Micromech. Microeng. 2001;11:726–732.

6. Torabinia M, Asgari P, Dakarapu U, et al. Onchip organic synthesis enabled by engine-and-cargo in an electrowetting-on-dielectric digital microfluidic device. Lab Chip. 2019;19:3054-3064.

7. Herranz-Blanco B, Ginestar E, Zhang H, et al. Microfluidics platform for glass capillaries and its application in droplet and nanoparticle fabrication. Int J Pharm. 2017;516(1–2):100-105.

8. Talebi S, Abedini A, Lele P, et al. Microfluidics- based measurement of solubility and diffusion coefficient of propane in bitumen. Fuel. 2017;210:23–31.

9. Mukherjee P, Nebuloni F, Gao H, et al. Rapid prototyping of soft lithography masters for microfluidic devices using dry film photoresist in a non-cleanroom setting. Micromachines. 2019;10(3):192.

10. Ivanov SV, Trachevskii VV, Stolyarova NV, et al. Plasmochemical modification of polymer surfaces. Rus J Appl Chem. 2006;79:445–447.

11. Kim DNH, Kim KT, Kim C, et al. Soft lithography fabrication of index-matched microfluidic devices for reducing artifacts in fluorescence and quantitative phase imaging. Microfluid Nanofluid. 2018;22:2.

12. Costa PF, Albers HJ, Linssen JEA, et al. Mimicking arterial thrombosis in a 3D-printed microfluidic in vitro vascular model based on computed tomography angiography data. Lab on a Chip. 2017;17(16):2785–2792.

13. Prabhakar A, Agrawal M, Mishra N, et al. Cost-effective smart microfluidic device with immobilized silver nanoparticles and embedded UV-light sources for synergistic water disinfection effects. RSC Advances. 2020;10(30):17479–17485.

14. Lopez C, Oza G, Casannova JR, et al. Proposal to Develop a Microfluidic Platform with GMR Sensors and the Use of Magnetic Nanoparticles in Order to Detect Cancerous Cells: Preliminary experimentation. Global Medical Engineering Physics Exchanges/ Pan American Health Care Exchanges (GMEPE/PAHCE). 26-31 March 2019: 18691807.

15. Hao N, Nie Y, Zhang JXJ. Microfluidic synthesis of functional inorganic micro-/nanoparticles and applications in biomedical engineering. International Materials Reviews. 2018;63(8):461-487.

16. Lin WZS, Malmstadt N. Liposome production and concurrent loading of drug simulants by microfluidic hydrodynamic focusing. Eur Biophys J. 2019;48(6):549-558.

17. Wang Y, Seidel M. Strategy for fast manufacturing of 3D hydrodynamic focusing multilayer microfluidic chips and its application for flow-based synthesis of gold nanoparticles. Microfluid Nanofluid. 2021;25:64.

18. Sounart TL, Safier PA, Voigt JA, et al. Spatially- resolved analysis of nanoparticle nucleation and growth in a microfluidic reactor. Lab Chip. 2007;7:908–915.

19. Tofighi G, Lichtenberg H, Pesek J, et al. Continuous microfluidic synthesis of colloidal ultrasmall gold nanoparticles: in situ study of the early reaction stages and application for catalysis. React. Chem. Eng. 2017;2:876–884.

20. Haoa N, Xua Z, Niea Y, et al. Microfluidics-enabled rational design of ZnO micro-/nanoparticles withenhanced photocatalysis, cytotoxicity, and piezoelectric properties. Chem Eng J. 2019;378:122222.

21. Zhang Y, Tong X, Yang L, et al. A herringbone mixer based microfluidic device HBEXO-chip for purifying tumor-derived exosomes and establishing miRNA signature in pancreatic cancer. Sensors and Actuators B: Chemical. 2021;332:129511.

22. Christopher GF, Anna SL. Microfluidic methods for generating continuous droplet streams. J Phys D: Appl Phys. 2007;40:R319.

23. Schimel TM, Nguyen MA, Sarles SA, et al. Pressure-driven generation of complex microfluidic droplet networks. Microfluidics and Nanofluidics. 2021;25:78.

24. Xie T, Wang P, Wu L, et al. A hand-powered microfluidic system for portable and low-waste sample discretization. Lab on a Chip. 2021;21:3429-3437.

25. Davis JJ, Padalino M, Kaplitz AS, et al. Utility of low-cost, miniaturized peristaltic and Venturi pumps in droplet microfluidics. Analytica Chimica Acta. 2021;1151:338230.

26. Khizar S, Halima HB, Ahmad NM, et al. Magnetic nanoparticles in microfluidic and sensing: From transport to detection. Electrophoresis. 2020;41(13-14):1206-1224.

27. Abedini-Nassab R, Miandoab MP, Şaşmaz M. Microfluidic Synthesis, Control, and Sensing of Magnetic Nanoparticles: A Review. Micromachines (Basel). 2021;12(7):768.

28. Bemetz J, Wegemann A, Saatchi K, et al. Microfluidic-Based Synthesis of Magnetic Nanoparticles Coupled with Miniaturized NMR for Online Relaxation Studies. Anal Chem. 2018;90(16):9975-9982.

29. Hermann CA, Mayer M, Griesche C, et al. Microfluidic-enabled magnetic labelling of nanovesicles for bioanalytical applications. Analyst. 2021;146(3):997-1003.

30. Rao L, Cai B, Bu LL, et al. Microfluidic Electroporation- Facilitated Synthesis of Erythrocyte Membrane- Coated Magnetic Nanoparticles for Enhanced Imaging-Guided Cancer Therapy. ACS Nano. 2017;11(4): 3496-3505.

31. Ma J, Yi C, Li CW. Facile synthesis and functionalization of color-tunable Ln3+-doped KGdF4 nanoparticles on a microfluidic platform. Mater Sci Eng C Mater Biol Appl. 2020;108:110381.

32. Мелерзанов А, Москалев А, Жаров В. Прецизионная медицина и молекулярная тераностика. Врач. 2016;2:11-14.

33. Stratified, personalised or P4 medicine: a new direction for placing the patient at the centre of healthcare and health education (Technical report). Academy of Medical Sciences, 2015. p. 37.

34. Papavassiliou AG. Transcription-factormodulating agents: precision and selectivity in drug design. Mol Med Today. 1998;4(8):358-66.

35. Kalash RS, Lakshmanan VK, Cho CS, et al. Theranostics. In: Mitsuhiro Ebara. Biomaterials Nanoarchitectonics. Elsevier Inc., 2016:197–215.

36. Mosayebi J, Kiyasatfar M, Laurent S. Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications. Adv. Healthcare Mater. 2017;6:1700306.

37. Khositanon C, Adpakpang K, Bureekaew S, et al. Continuous-flow purification of silver nanoparticles and its integration with flow synthesis. J Flow Chem. 2020;10:353–362.

38. Chastek TQ, Iida K, Amis EJ, et al. A microfluidic platform for integrated synthesis and dynamic light scattering measurement of block copolymer micelles. Lab on a Chip. 2008;8(6):950–957.

39. Perro A, Lebourdon G, Henry S, et al. Combining microfluidics and FT-IR spectroscopy: towards spatially resolved information on chemical processes. React. Chem. Eng. 2016;1:577–594.

40. Măriuţa D, Colin S, Barrot-Lattes C, et al. Miniaturization of fluorescence sensing in optofluidic devices. Microfluid Nanofluid. 2020;24:65.

41. Ryu G, Huang J, Hofmann O, et al. Highly sensitive fluorescence detection system for microfluidic lab-on-a-chip. Lab on a Chip. 2011;11(9):1664.

42. Bates KE, Lu H. Optics-Integrated Microfluidic Platforms for Biomolecular Analyses. Biophysical Journal. 2016;110(8):1684-1697.

43. Li Z, Ju R, Sekine S, et al. All-in-one microfluidic device for on-site diagnosis of pathogens based on integrated continuous flow PCR and electrophoresis biochip. Lab Chip. 2019;19:2663–2668.

44. Bomers M, Charlot B, Barho F, et al. Microfluidic surface-enhanced infrared spectroscopy with semiconductor plasmonics for the fingerprint region. React Chem Eng. 2020;5:124.

45. Vaccari L, Birarda G, Businaro L, et al. Infrared Microspectroscopy of Live Cells in Microfluidic Devices (MD-IRMS): Toward a Powerful Label-Free Cell-Based Assay. Analytical Chemistry. 2012;84(11):4768–4775.

46. Xiao L, Zhang P, Li W, et al. Multi-angle Fiber DLS system Based on Microfluidics Technology. International Applied Computational Electromagnetics Society Symposium. China (ACES). 2019:19565492.

47. McArdle H, Jimenez-Mateos EM, Raoof R, et al. “TORNADO” – Theranostic One-Step RNA Detector; microfluidic disc for the direct detection of microRNA-134 in plasma and cerebrospinal fluid. Sci Rep. 2017;7:1750.

48. Kaur G, Tomar M, Gupta V. Development of a microfluidic electrochemical biosensor: Prospect for point-of-care cholesterol monitoring. Sensors and Actuators B: Chemical. 2018;261:460–466.

49. Shin SR, Kilic T, Zhang YS, et al. Label-Free and Regenerative Electrochemical Microfluidic Biosensors for Continual Monitoring of Cell Secretomes. Advanced Science. 2017;4(5):1600522.

50. Kirsch J, Siltanen C, Zhou Q, et al. Biosensor technology: recent advances in threat agent detection and medicine Chem Soc Rev. 2013;42:8733–8768.

51. Ghrera AS, Pandey CM, Malhotra BD. Multiwalled carbon nanotube modified microfluidic-based biosensor chip for nucleic acid detection. Sensors and Actuators B: Chemical. 2018;266:329–336.

52. Jiang H, Jiang D, Zhu P, et al. A novel mast cell co-culture microfluidic chip for the electrochemical evaluation of food allergen. Biosensors and Bioelectronics. 2016; 83: 126–133.

53. Campaña A, Florez S, Noguera M, et al. Enzyme-Based Electrochemical Biosensors for Microfluidic Platforms to Detect Pharmaceutical Residues in Wastewater. Biosensors. 2019;9(1):41.

54. Arora A, Simone G, Salieb-Beugelaar GB, et al. Latest Developments in Micro Total Analysis Systems. Analytical Chemistry. 2010;82(12):4830–4847.

55. Fernández-la-Villa A, Pozo-Ayuso DF, CastañoÁlvarez M. Microfluidics and electrochemistry: An emerging tandem for next-generation analytical microsystems. Current Opinion in Electrochemistry. 2019;15:175-185.

56. Haeberle S, Zengerle R. Microfluidic platforms for lab-on-a-chip applications. Lab Chip. 2007;7:1094–1110.

57. Rackus DG, Shamsi MH, Wheeler AR. Electrochemistry, biosensors and microfluidics: a convergence of fields. Chemical Society Reviews. 2015;44(15):5320–5340.

58. Jin Z, Liu Y, Fan W, et al. Integrating Flexible Electrochemical Sensor into Microfluidic Chip for Simulating and Monitoring Vascular Mechanotransduction. Small. 2019:1903204.

59. Wang S, Zheng L, Cai G, et al. A microfluidic biosensor for online and sensitive detection of Salmonella typhimurium using fluorescence labeling and smartphone video processing. Biosensors and Bioelectronics. 2019:111333.

60. Ahadian S, Civitarese R, Bannerman D, et al. Organ-On-A-Chip Platforms: A Convergence of Advanced Materials, Cells, and Microscale Technologies. Adv Healthc Mater. 2018;7:1700506.

61. Asif A, Kim KH, Jabbar F, et al. Real-time sensors for live monitoring of disease and drug analysis in microfluidic model of proximal tubule. Microfluid Nanofluid. 2020;24:43.

62. Khetani S, Yong KW, Kollath, VO, et al. Engineering Shelf-Stable Coating for Microfluidic Organon- a-Chip using Bioinspired Catecholamine Polymers. ACS Appl Mater Interfaces. 2020;12(6):6910-6923.

63. Arefi SMA, Tony Yang CWT, Sin DD, et al. Simulation of nanoparticle transport and adsorption in a microfluidic lung-on-a-chip device. Biomicrofluidics. 2020;14(4):044117.

64. Xia Y, Chen Y, Tang Y et al. A Smartphone-based Point-of-care Microfluidic Platform Fabricated with ZnO Nanorod Template for Colorimetric Virus Detection. ACS Sensors. 2019 ;4(12):3298-3307.

65. Wang Y, Wang P, Qin J. Microfluidic Organs-ona- Chip for Modeling Human Infectious Diseases. Acc. Chem. Res. 2021;54(18):3550–3562.

66. Olofsson S, Brittain-Long R, Andersson LM, et al. PCR for detection of respiratory viruses: seasonal variations of virus infections. Expert Rev Anti Infect Ther. 2011;9(8):615–626.

67. Saijo M, Morikawa S, Kurane I. Real-time quantitative polymerase chain reaction for virus infection diagnostics. Expert Opin Med Diagn. 2008;2(10):1155–1171.

68. Whitman JD, Hiatt J, Mowery CT, et al. Evaluation of SARS-CoV-2 serology assays reveals a range of test performance. Nat Biotechnol. 2020;38(10):1174–1183.

69. Peeling RW, Wedderburn CJ, Garcia PJ, et al. Serology testing in the COVID-19 pandemic response. Lancet. 2020;20(9):E245–E249.

70. Derakhshan MA, Amani A, Faridi-Majidi R. Stateof- the-Art of Nanodiagnostics and Nanotherapeutics against SARS-CoV-2. ACS Appl Mater Interfaces. 2021;13(13):14816–14843.

71. Bellan LM, Wu D, Langer RS. Current trends in nanobiosensor technology. Wiley Interdiscip. Rev Nanomed Nanobiotechnol. 2011;3(3):229–246.

72. Talebian S, Wallace GG, Schroeder A, el at. Nanotechnology- based disinfectants and sensors for SARSCoV-2. Nat Nanotechnol. 2020;15(8):618–621.

73. Saxena A, Khare D, Agrawal S et al. Recent advances in materials science: a reinforced approach toward challenges against COVID-19. Emergent Mater. 2021;4(1):57–73.

74. Chintagunta AD, M SK, Nalluru S, et al. Nanotechnology: An emerging approach to combat COVID-19. Emergent Mater. 2021;4:119–130.

75. Hassanzadeh P. Nanotheranostics against COVID-19: From multivalent to immune-targeted materials. J Control Release. 2020;328:112–126.

76. Akhmedova DA, Shatalov DO, Ivanov IS, et al. The use of microfluidic hardware in the synthesis of oligohexamethylene guanidine derivatives. Fine Chemical Technologies. 2021;16(4):307-317.

77. Woolley AT, Hadley В, Landre P, et al. Functional integration of PCR amplification and capillary electrophoresis in a microfabricated DNA analysis device. Anal. Chem. 1996;68(23):4081–4086.

78. Кухтевич И.В., Евстрапов А.А., Букатин А.С. Микрофлюидные устройства для исследований клеток (обзор). Научное приборостроение. 2013;4:66–75.

79. Занавескин М.Л., Миронова А.А., Попов А.М. и др. Применение микрофлюидной технологии для синтеза радиофармпрепаратов, меченных 18F. Медицинская физика. 2013;4:44-51.