Nanoparticles are considered to be a powerful approach for the delivery of poorly watersoluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, ...Nanoparticles are considered to be a powerful approach for the delivery of poorly watersoluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, rapid and scalable method, the flash nanoprecipitation(FNP) has been widely used to fabricate these drug nanoparticles, including pure drug nanocrystals, polymeric micelles,polymeric nanoparticles, solid lipid nanoparticles, and polyelectrolyte complexes. This review introduces the application of FNP to produce poorly water-soluble drug nanoparticles by controllable mixing devices, such as confined impinging jets mixer(CIJM), multi-inlet vortex mixer(MIVM) and many other microfluidic mixer systems. The formation mechanisms and processes of drug nanoparticles by FNP are described in detail. Then, the controlling of supersaturation level and mixing rate during the FNP process to tailor the ultrafine drug nanoparticles as well as the influence of drugs, solvent, anti-solvent, stabilizers and temperature on the fabrication are discussed. The ultrafine and uniform nanoparticles of poorly watersoluble drug nanoparticles prepared by CIJM, MIVM and microfluidic mixer systems are reviewed briefly. We believe that the application of microfluidic mixing devices in laboratory with continuous process control and good reproducibility will be benefit for industrial formulation scale-up.展开更多
In this work, monodisperse giant polymersomes are fabricated by dewetting of water-in-oil-in-water double emulsion droplets which are assembled by amphiphilic block copolymer molecules in a microfluidic device. The de...In this work, monodisperse giant polymersomes are fabricated by dewetting of water-in-oil-in-water double emulsion droplets which are assembled by amphiphilic block copolymer molecules in a microfluidic device. The dewetting process can be tuned by solvation between solvent and amphiphilic block copolymer to get polymersomes with controllable morphology. Good solvent (chloroform and toluene) hinders dewetting process of double emulsion droplets and gets acornlike polymersomes or patched polymersomes. On the other hand, poor solvent (hexane) accelerates the dewetting process and achieves complete separation of inner water phase from oil phase to form complete bilayer polymersomes. In addition, twin polymersomes with bilayer membrane structure are formed by this facile method. The formation mechanism for different polymersomes is discussed in detail.展开更多
Nanomaterials show promising opportunities to address clinical problems (such as insufficient capture of circulating tumor cells; CTCs) via the high surface area-to-volume ratio and high affinity for biological cell...Nanomaterials show promising opportunities to address clinical problems (such as insufficient capture of circulating tumor cells; CTCs) via the high surface area-to-volume ratio and high affinity for biological cells. However, how to apply these nanomaterials as a nano-bio interface in a microfluidic device for efficient CTC capture with high specificity remains a challenge. In the present work, we first found that a titanium dioxide (TiO2) nanorod array that can be conveniently prepared on multiple kinds of substrates has high affinity for tumor cells. Then, the TiO2 nanorod array was vertically grown on the surface of a microchannel with hexagonally patterned Si micropillars via a hydrothermal reaction, forming a new kind of a micro-nano 3D hierarchically structured microfluidic device. The vertically grown TiO2 nanorod array was used as a sensitive nano-bio interface of this 3D hierarchically structured microfluidic device, which showed high efficiency of CTC capture (76.7% ± 7.1%) in an artificial whole-blood sample.展开更多
A poly(dimethylsiloxane)(PDMS)/glass hybrid microchip for on-line solid phase extraction (SPE) and electrophoresis separation has been developed and evaluated. The SPE microchannel was crossed to the electrophoresis m...A poly(dimethylsiloxane)(PDMS)/glass hybrid microchip for on-line solid phase extraction (SPE) and electrophoresis separation has been developed and evaluated. The SPE microchannel was crossed to the electrophoresis microchannel. All the microfluidic channels were etched on the glass substrate. The magnetic microspheres were coated with hydroxyl-terminated poly-dimethylsiloxane (PDMS-OH) serving as extraction phase,which could be conveniently immobilized into the sample pretreatment channel by magnetic field. The PDMS-OH microspheres were mobilized into and out of the pretreatment channel by injection flow. The 0.1 μmol/L solution of fluorescence isothiocyanate (FITC)-labeled phenylalanine (Phe) was electrically injected into the SPE channel and extracted onto the PDMS-OH microspheres bed. The enriched FITC-labeled Phe was electrically eluted by 9 mmol/L sodium acetate containing 10% acetonitrile and electrically driven into the electrophoresis channel and then separated. The preconcentration factor could reach 87.5 after sufficient extraction. A linear preconcentration curve was obtained with the initial FITC-labeled Phe concentration ranging from 6 nmol/L to 300 nmol/L (R2=0.9922) with 200 s loading time. The detection limit (S/N=3) for the FITC-labeled Phe was 3 nmol/L.展开更多
基金supported by Research Committee of University of Macao (MYRG2017-00200-ICMS)Macao Science and Technology Development Fund (FDCT 0013/2018/A1)
文摘Nanoparticles are considered to be a powerful approach for the delivery of poorly watersoluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, rapid and scalable method, the flash nanoprecipitation(FNP) has been widely used to fabricate these drug nanoparticles, including pure drug nanocrystals, polymeric micelles,polymeric nanoparticles, solid lipid nanoparticles, and polyelectrolyte complexes. This review introduces the application of FNP to produce poorly water-soluble drug nanoparticles by controllable mixing devices, such as confined impinging jets mixer(CIJM), multi-inlet vortex mixer(MIVM) and many other microfluidic mixer systems. The formation mechanisms and processes of drug nanoparticles by FNP are described in detail. Then, the controlling of supersaturation level and mixing rate during the FNP process to tailor the ultrafine drug nanoparticles as well as the influence of drugs, solvent, anti-solvent, stabilizers and temperature on the fabrication are discussed. The ultrafine and uniform nanoparticles of poorly watersoluble drug nanoparticles prepared by CIJM, MIVM and microfluidic mixer systems are reviewed briefly. We believe that the application of microfluidic mixing devices in laboratory with continuous process control and good reproducibility will be benefit for industrial formulation scale-up.
基金financially supported by the National Natural Science Foundation of China(No.50633030,Innovation Group:50921062)
文摘In this work, monodisperse giant polymersomes are fabricated by dewetting of water-in-oil-in-water double emulsion droplets which are assembled by amphiphilic block copolymer molecules in a microfluidic device. The dewetting process can be tuned by solvation between solvent and amphiphilic block copolymer to get polymersomes with controllable morphology. Good solvent (chloroform and toluene) hinders dewetting process of double emulsion droplets and gets acornlike polymersomes or patched polymersomes. On the other hand, poor solvent (hexane) accelerates the dewetting process and achieves complete separation of inner water phase from oil phase to form complete bilayer polymersomes. In addition, twin polymersomes with bilayer membrane structure are formed by this facile method. The formation mechanism for different polymersomes is discussed in detail.
基金The authors are thankful for funding from the National Natural Science Foundation of China (Nos. 51402063, 51432005, 61405040, 61505010, 51502018, 31270022, and 81471784), the "100 Talents Program" of the Chinese Academy of Sciences, Beijing City Committee of science and technology (No. Z151100003315010), Beijing Natural Science Foundation (Nos. 2164077 and 2164076), the Fundamental Research Funds of Shandong University (No. 2014QY003), and the Youth Innovation Promotion Association of the Chinese Academy of Sciences (No. 2015023). The authors also acknowledge the support from the"thousands talents" program for pioneer researchers and his innovation team, and support from the President Funding of the Chinese Academy of Sciences.
文摘Nanomaterials show promising opportunities to address clinical problems (such as insufficient capture of circulating tumor cells; CTCs) via the high surface area-to-volume ratio and high affinity for biological cells. However, how to apply these nanomaterials as a nano-bio interface in a microfluidic device for efficient CTC capture with high specificity remains a challenge. In the present work, we first found that a titanium dioxide (TiO2) nanorod array that can be conveniently prepared on multiple kinds of substrates has high affinity for tumor cells. Then, the TiO2 nanorod array was vertically grown on the surface of a microchannel with hexagonally patterned Si micropillars via a hydrothermal reaction, forming a new kind of a micro-nano 3D hierarchically structured microfluidic device. The vertically grown TiO2 nanorod array was used as a sensitive nano-bio interface of this 3D hierarchically structured microfluidic device, which showed high efficiency of CTC capture (76.7% ± 7.1%) in an artificial whole-blood sample.
基金Supported by the National Natural Science Foundation of China (Grant Nos. 20605018 & 30772006) the Beijing Natural Science Foundation (Grant No. 2072018)
文摘A poly(dimethylsiloxane)(PDMS)/glass hybrid microchip for on-line solid phase extraction (SPE) and electrophoresis separation has been developed and evaluated. The SPE microchannel was crossed to the electrophoresis microchannel. All the microfluidic channels were etched on the glass substrate. The magnetic microspheres were coated with hydroxyl-terminated poly-dimethylsiloxane (PDMS-OH) serving as extraction phase,which could be conveniently immobilized into the sample pretreatment channel by magnetic field. The PDMS-OH microspheres were mobilized into and out of the pretreatment channel by injection flow. The 0.1 μmol/L solution of fluorescence isothiocyanate (FITC)-labeled phenylalanine (Phe) was electrically injected into the SPE channel and extracted onto the PDMS-OH microspheres bed. The enriched FITC-labeled Phe was electrically eluted by 9 mmol/L sodium acetate containing 10% acetonitrile and electrically driven into the electrophoresis channel and then separated. The preconcentration factor could reach 87.5 after sufficient extraction. A linear preconcentration curve was obtained with the initial FITC-labeled Phe concentration ranging from 6 nmol/L to 300 nmol/L (R2=0.9922) with 200 s loading time. The detection limit (S/N=3) for the FITC-labeled Phe was 3 nmol/L.