Sonoporation mediated by microbubbles is being extensively studied as a promising technology to facilitate gene/drug delivery to cells. However, the theoretical study regarding the mechanisms involved in sonoporation ...Sonoporation mediated by microbubbles is being extensively studied as a promising technology to facilitate gene/drug delivery to cells. However, the theoretical study regarding the mechanisms involved in sonoporation is still in its infancy.Microstreaming generated by pulsating microbubble near the cell membrane is regarded as one of the most important mechanisms in the sonoporation process. Here, based on an encapsulated microbubble dynamic model with considering nonlinear rheological effects of both shell elasticity and viscosity, the microstreaming velocity field and shear stress generated by an oscillating microbubble near the cell membrane are theoretically simulated. Some factors that might affect the behaviors of microstreaming are thoroughly investigated, including the distance between the bubble center and cell membrane（d）, shell elasticity（χ）, and shell viscosity（κ）. The results show that（i） the presence of cell membrane can result in asymmetric microstreaming velocity field, while the constrained effect of the membrane wall decays with increasing the bubble-cell distance;（ii） the bubble resonance frequency increases with the increase in d and χ, and the decrease in κ,although it is more dominated by the variation of shell elasticity; and（iii） the maximal microstreaming shear stress on the cell membrane increases rapidly with reducing the d, χ, and κ. The results suggest that microbubbles with softer and less viscous shell materials might be preferred to achieve more efficient sonoporation outcomes, and it is better to have bubbles located in the immediate vicinity of the cell membrane.展开更多
Analyzing undiluted whole human blood is a challenge due to its complex composition of hematopoietic cellular populations,nucleic acids,metabolites,and proteins.We present a novel multi-functional microfluidic acousti...Analyzing undiluted whole human blood is a challenge due to its complex composition of hematopoietic cellular populations,nucleic acids,metabolites,and proteins.We present a novel multi-functional microfluidic acoustic streaming platform that enables sorting,enrichment and in situ identification of cellular subsets from whole blood.This single device platform,based on lateral cavity acoustic transducers(LCAT),enables(1)the sorting of undiluted donor whole blood into its cellular subsets(platelets,RBCs,and WBCs),(2)the enrichment and retrieval of breast cancer cells(MCF-7)spiked in donor whole blood at rare cell relevant concentrations(10 mL^(−1)),and(3)on-chip immunofluorescent labeling for the detection of specific target cellular populations by their known marker expression patterns.Our approach thus demonstrates a compact system that integrates upstream sample processing with downstream separation/enrichment,to carry out multi-parametric cell analysis for blood-based diagnosis and liquid biopsy blood sampling.展开更多
基金Projects supported by the National Basic Research Program,China(Grant No.2011CB707900)the National Natural Science Foundation of China(Grant Nos.81127901,81227004,81271589,11374155,11161120324,11074123,11174141,11274170,11104140,11474001,and 11474161)+1 种基金the National High Tech Research and Development Program,China(Grant No.2012AA022702)the Program for New Century Excellent Talents in University of Ministry of Education of China(Grant No.NCET-11-0236)
文摘Sonoporation mediated by microbubbles is being extensively studied as a promising technology to facilitate gene/drug delivery to cells. However, the theoretical study regarding the mechanisms involved in sonoporation is still in its infancy.Microstreaming generated by pulsating microbubble near the cell membrane is regarded as one of the most important mechanisms in the sonoporation process. Here, based on an encapsulated microbubble dynamic model with considering nonlinear rheological effects of both shell elasticity and viscosity, the microstreaming velocity field and shear stress generated by an oscillating microbubble near the cell membrane are theoretically simulated. Some factors that might affect the behaviors of microstreaming are thoroughly investigated, including the distance between the bubble center and cell membrane（d）, shell elasticity（χ）, and shell viscosity（κ）. The results show that（i） the presence of cell membrane can result in asymmetric microstreaming velocity field, while the constrained effect of the membrane wall decays with increasing the bubble-cell distance;（ii） the bubble resonance frequency increases with the increase in d and χ, and the decrease in κ,although it is more dominated by the variation of shell elasticity; and（iii） the maximal microstreaming shear stress on the cell membrane increases rapidly with reducing the d, χ, and κ. The results suggest that microbubbles with softer and less viscous shell materials might be preferred to achieve more efficient sonoporation outcomes, and it is better to have bubbles located in the immediate vicinity of the cell membrane.
基金This work was supported by the NSF Center for Advanced Design and Manufacturing of Integrated Microfluidics(CADMIM)(Award Nos.IIP-1362165 and IIP-1362048)Schlumberger Faculty for the Future Award(Award No.SF-202940)the National Cancer Institute of the National Institutes of Health under award no.P30CA062203.
文摘Analyzing undiluted whole human blood is a challenge due to its complex composition of hematopoietic cellular populations,nucleic acids,metabolites,and proteins.We present a novel multi-functional microfluidic acoustic streaming platform that enables sorting,enrichment and in situ identification of cellular subsets from whole blood.This single device platform,based on lateral cavity acoustic transducers(LCAT),enables(1)the sorting of undiluted donor whole blood into its cellular subsets(platelets,RBCs,and WBCs),(2)the enrichment and retrieval of breast cancer cells(MCF-7)spiked in donor whole blood at rare cell relevant concentrations(10 mL^(−1)),and(3)on-chip immunofluorescent labeling for the detection of specific target cellular populations by their known marker expression patterns.Our approach thus demonstrates a compact system that integrates upstream sample processing with downstream separation/enrichment,to carry out multi-parametric cell analysis for blood-based diagnosis and liquid biopsy blood sampling.
