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1.
Nat Biomed Eng ; 3(12): 961-973, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31712645

RESUMO

Dysregulated leukocyte responses underlie the pathobiology of sepsis, which is a leading cause of death. However, measures of leukocyte function are not routinely available in clinical care. Here we report the development and testing of an inertial microfluidic system for the label-free isolation and downstream functional assessment of leukocytes from 50 µl of peripheral blood. We used the system to assess leukocyte phenotype and function in serial samples from 18 hospitalized patients with sepsis and 10 healthy subjects. The sepsis samples had significantly higher levels of CD16dim and CD16- neutrophils and CD16+ 'intermediate' monocytes, as well as significantly lower levels of neutrophil-elastase release, O2- production and phagolysosome formation. Repeated sampling of sepsis patients over 7 days showed that leukocyte activation (measured by isodielectric separation) and leukocyte phenotype and function were significantly more predictive of the clinical course than complete-blood-count parameters. We conclude that the serial assessment of leukocyte function in microlitre blood volumes is feasible and that it provides significantly more prognostic information than leukocyte counting.


Assuntos
Leucócitos , Técnicas Analíticas Microfluídicas/métodos , Sepse/sangue , Sepse/diagnóstico , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Proteínas Ligadas por GPI , Humanos , Contagem de Leucócitos , Elastase de Leucócito/sangue , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Pessoa de Meia-Idade , Monócitos , Neutrófilos , Fenótipo , Receptores de IgG , Adulto Jovem
2.
Small ; 14(50): e1803585, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30369043

RESUMO

3D structures with complex geometric features at the microscale, such as microparticles and microfibers, have promising applications in biomedical engineering, self-assembly, and photonics. Fabrication of complex 3D microshapes at scale poses a unique challenge; high-resolution methods such as two-photon-polymerization have print speeds too low for high-throughput production, while top-down approaches for bulk processing using microfabricated template molds have limited control of microstructure geometries over multiple axes. Here, a method for microshape fabrication is presented that combines a thermally drawn transparent fiber template with a masked UV-photopolymerization approach to enable biaxial control of microshape fabrication. Using this approach, high-resolution production of complex microshapes not producible using alternative methods is demonstrated, such as octahedrons, dreidels, and axially asymmetric fibers, at throughputs as high as 825 structures/minute. Finally, the fiber template is functionalized with conductive electrodes to enable hierarchical subparticle localization using dielectrophoretic forces.


Assuntos
Hidrogéis/química , Microfluídica/métodos , Microtecnologia
3.
Proc Natl Acad Sci U S A ; 115(46): E10830-E10838, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30373819

RESUMO

Traditional fabrication techniques for microfluidic devices utilize a planar chip format that possesses limited control over the geometry of and materials placement around microchannel cross-sections. This imposes restrictions on the design of flow fields and external forces (electric, magnetic, piezoelectric, etc.) that can be imposed onto fluids and particles. Here we report a method of fabricating microfluidic channels with complex cross-sections. A scaled-up version of a microchannel is dimensionally reduced through a thermal drawing process, enabling the fabrication of meters-long microfluidic fibers with nonrectangular cross-sectional shapes, such as crosses, five-pointed stars, and crescents. In addition, by codrawing compatible materials, conductive domains can be integrated at arbitrary locations along channel walls. We validate this technology by studying unexplored regimes in hydrodynamic flow and by designing a high-throughput cell separation device. By enabling these degrees of freedom in microfluidic device design, fiber microfluidics provides a method to create microchannel designs that are inaccessible using planar techniques.


Assuntos
Técnicas Analíticas Microfluídicas/métodos , Microfluídica/instrumentação , Microfluídica/métodos , Separação Celular , Desenho de Equipamento/métodos , Hidrodinâmica , Dispositivos Lab-On-A-Chip
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