The migration mode transition of cancer cell enhances its invasive capability and the drug resistance,where physical confinement of cell microenvironment has been revealed to induce the mesenchymal-amoeboid transition...The migration mode transition of cancer cell enhances its invasive capability and the drug resistance,where physical confinement of cell microenvironment has been revealed to induce the mesenchymal-amoeboid transition(MAT).However,most existing studies are performed in PDMS microchannels,of which the stiffness is much higher than that of most mammalian tissues.Therefore,the amoeboid migration transition observed in these studies is actually induced by the synergistic effect of matrix stiffness and confinement.Since the stiffness of cell microenvironment has been reported to influence the cell migration in 2D substrate,the decoupling of stiffness and confinement effects is thus in need for elucidating the underlying mechanism of MAT.However,it is technically challenging to construct microchannels with physiologically relevant stiffness and channel size,where existing microchannel platforms with physiological relevance stiffness are all with>10μm channel width.Such size is too wide to mimic the physical confinement that migrating cancer cells confront in vivo,and also larger than the width of PDMS channel,in which the MAT of cancer cell was observed.Therefore,an in vitro cell migration platform,which could mimic both stiffness and confinement of the native physical microenvironment during cancer metastasis,could profoundly contribute to researches on cancer cell migration and cellular mechanotransduction.In this paper,we overcome the limitations of engineering soft materials in microscale by combining the collagen-alginate hydrogel with photolithography.This enables us to improve the accuracy of molded microchannel,and thus successfully construct a 3D microchannel platform,which matches the stiffness and width ranges of native environmental confinement that migrating cancer cells confront in vivo.The stiffness(0.3~20 kPa),confinement(channel width:3.5~14μm)and the adhesion ligand density of the microchannel can be tuned independently.Interestingly,using this platform,we observed that the migration speed of cancer cell is influenced by the synergistic effect of channel stiffness and width,and the increasing stiffness reverses the effect of channel width on the migration speed of cancer cells.In addition,MAT has a strong correlation with the channel stiffness.These findings make us reconsider the widely accepted hypothesis:physical confinement can induce MAT.Actually,this transition can only occur in stiff confined microenvironment not in soft one.For soft microchannels,the compliance of the channel walls could cause little cell/nucleus deformation,and the MAT could not be induced.To further investigate the mechanism of MAT,we developed a computational model to simulate the effect of nucleus deformation on MAT.With the model,we found that deforming the cell nuclear by decreasing the nucleus stiffness will reduce the cellmigration speed.This implies that nuclear stiffness plays an important role in the regulation of cancer migration speed and thus MAT in microchannels.The effect of channel stiffness on MAT and migration speed as observed in our experiment could partially explain previous findings reported in the literature,where the increasing matrix stiffness of tumor microenvironment promotes cancer metastasis.Our observations thus highlight the critical role of cell nuclear deformation not only in MAT,but also in regulating cellular mechanotransduction and cell-ECM interactions.This developed platform is capable of mimicking the native physical microenvironment during metastasis,providing a powerful tool for high-throughput screening applications and investigating the interaction between cancer migration and biophysical microenvironment.展开更多
A high-aspect-ratio microchannel heat exchanger based on multi-tool milling process was developed. Several slotting cutters were stacked together for simultaneously machining several high-aspect-ratio microchannels wi...A high-aspect-ratio microchannel heat exchanger based on multi-tool milling process was developed. Several slotting cutters were stacked together for simultaneously machining several high-aspect-ratio microchannels with manifold structures. On the basis of multi-tool milling process, the structural design of the manifold side height, microchannel length, width, number, and interval were analyzed. The heat transfer performances of high-aspect-ratio microchannel heat exchangers with two different manifolds were investigated by experiments, and the influencing factors were analyzed. The results indicate that the magnitude of heat transfer area per unit volume dominates the heat transfer performances of plate-type micro heat exchanger, while the velocity distribution between microchannels has little effects on the heat transfer performances.展开更多
This investigation numerically examined the combined impacts of different turbulator shapes,Al_(2)O_(3)/water nanofluid,and inclined magnetic field on the thermal behavior of micro-scale inclined forward-facing step(M...This investigation numerically examined the combined impacts of different turbulator shapes,Al_(2)O_(3)/water nanofluid,and inclined magnetic field on the thermal behavior of micro-scale inclined forward-facing step(MSIFFS).The length and height for all turbulators were considered 0.0979 and 0.5 mm,respectively,and the Reynolds number varied from 5000 to 10000.In order to compare the skin friction coefficient(SFC) and the heat transfer rate(HTR)simultaneously,the thermal performance factor parameter(TPF) was selected.The results show that all considered cases equipped with turbulators were thermodynamically more advantageous over the simple MSIFFS.Besides,using Al_(2)O_(3)/water nanofluid with different nanoparticles volume fractions(NVF) in the presence of inclined magnetic field(IMF)increased HTR.With an increment of NVF from 1% to 4% and magnetic field density(MFD) from 0.002 to 0.008 T,HTR and subsequently TPF improved.The best result was observed for MSIFFS equipped with a trapezoidal-shaped turbulator with 4% Al_(2)O_(3) in the presence of IMF(B=0.008 T).The TPF increased with the augmentation of Re,and the maximum value of it was 5.2366 for MSIFFS equipped with a trapezoidal-shaped turbulator with 4% Al_(2)O_(3),B=0.008 T,and Re=10000.展开更多
A Ti interlayer with thickness about 300 nm was sputtered on Cu microchannels, followed by an ultrasonic seeding with nanodiamond powders. Adherent diamond film with crystalline grains close to thermal equilibrium sha...A Ti interlayer with thickness about 300 nm was sputtered on Cu microchannels, followed by an ultrasonic seeding with nanodiamond powders. Adherent diamond film with crystalline grains close to thermal equilibrium shape was tightly deposited by hot-filament chemical vapor deposition(HF-CVD). The nucleation and growth of diamond were investigated with micro-Raman spectroscope and field emission scanning electron microscope(FE-SEM) with energy dispersive X-ray detector(EDX). Results show that the nucleation density is found to be up to 1010 cm-2. The enhancement of the nucleation kinetics can be attributed to the nanometer rough Ti interlayer surface. An improved absorption of nanodiamond particles is found, which act as starting points for the diamond nucleation during HF-CVD process. Furthermore, finite element simulation was conducted to understand the thermal management properties of prepared diamond/Cu microchannel heat sink.展开更多
基金financially supported by the National Natural Science Foundation of China ( 11532009, 11602191,21775117)the General Financial Grant from the China Postdoctoral Science Foundation ( 2016M592773)the High Level Returned Overseas Students Foundation ( [2018]642)
文摘The migration mode transition of cancer cell enhances its invasive capability and the drug resistance,where physical confinement of cell microenvironment has been revealed to induce the mesenchymal-amoeboid transition(MAT).However,most existing studies are performed in PDMS microchannels,of which the stiffness is much higher than that of most mammalian tissues.Therefore,the amoeboid migration transition observed in these studies is actually induced by the synergistic effect of matrix stiffness and confinement.Since the stiffness of cell microenvironment has been reported to influence the cell migration in 2D substrate,the decoupling of stiffness and confinement effects is thus in need for elucidating the underlying mechanism of MAT.However,it is technically challenging to construct microchannels with physiologically relevant stiffness and channel size,where existing microchannel platforms with physiological relevance stiffness are all with>10μm channel width.Such size is too wide to mimic the physical confinement that migrating cancer cells confront in vivo,and also larger than the width of PDMS channel,in which the MAT of cancer cell was observed.Therefore,an in vitro cell migration platform,which could mimic both stiffness and confinement of the native physical microenvironment during cancer metastasis,could profoundly contribute to researches on cancer cell migration and cellular mechanotransduction.In this paper,we overcome the limitations of engineering soft materials in microscale by combining the collagen-alginate hydrogel with photolithography.This enables us to improve the accuracy of molded microchannel,and thus successfully construct a 3D microchannel platform,which matches the stiffness and width ranges of native environmental confinement that migrating cancer cells confront in vivo.The stiffness(0.3~20 kPa),confinement(channel width:3.5~14μm)and the adhesion ligand density of the microchannel can be tuned independently.Interestingly,using this platform,we observed that the migration speed of cancer cell is influenced by the synergistic effect of channel stiffness and width,and the increasing stiffness reverses the effect of channel width on the migration speed of cancer cells.In addition,MAT has a strong correlation with the channel stiffness.These findings make us reconsider the widely accepted hypothesis:physical confinement can induce MAT.Actually,this transition can only occur in stiff confined microenvironment not in soft one.For soft microchannels,the compliance of the channel walls could cause little cell/nucleus deformation,and the MAT could not be induced.To further investigate the mechanism of MAT,we developed a computational model to simulate the effect of nucleus deformation on MAT.With the model,we found that deforming the cell nuclear by decreasing the nucleus stiffness will reduce the cellmigration speed.This implies that nuclear stiffness plays an important role in the regulation of cancer migration speed and thus MAT in microchannels.The effect of channel stiffness on MAT and migration speed as observed in our experiment could partially explain previous findings reported in the literature,where the increasing matrix stiffness of tumor microenvironment promotes cancer metastasis.Our observations thus highlight the critical role of cell nuclear deformation not only in MAT,but also in regulating cellular mechanotransduction and cell-ECM interactions.This developed platform is capable of mimicking the native physical microenvironment during metastasis,providing a powerful tool for high-throughput screening applications and investigating the interaction between cancer migration and biophysical microenvironment.
基金Projects(50675070 50805052) supported by the National Nature Science Foundation of China+1 种基金Projects(07118064 8451064101000320) supported by the Natural Science Foundation of Guangdong Province
文摘A high-aspect-ratio microchannel heat exchanger based on multi-tool milling process was developed. Several slotting cutters were stacked together for simultaneously machining several high-aspect-ratio microchannels with manifold structures. On the basis of multi-tool milling process, the structural design of the manifold side height, microchannel length, width, number, and interval were analyzed. The heat transfer performances of high-aspect-ratio microchannel heat exchangers with two different manifolds were investigated by experiments, and the influencing factors were analyzed. The results indicate that the magnitude of heat transfer area per unit volume dominates the heat transfer performances of plate-type micro heat exchanger, while the velocity distribution between microchannels has little effects on the heat transfer performances.
文摘This investigation numerically examined the combined impacts of different turbulator shapes,Al_(2)O_(3)/water nanofluid,and inclined magnetic field on the thermal behavior of micro-scale inclined forward-facing step(MSIFFS).The length and height for all turbulators were considered 0.0979 and 0.5 mm,respectively,and the Reynolds number varied from 5000 to 10000.In order to compare the skin friction coefficient(SFC) and the heat transfer rate(HTR)simultaneously,the thermal performance factor parameter(TPF) was selected.The results show that all considered cases equipped with turbulators were thermodynamically more advantageous over the simple MSIFFS.Besides,using Al_(2)O_(3)/water nanofluid with different nanoparticles volume fractions(NVF) in the presence of inclined magnetic field(IMF)increased HTR.With an increment of NVF from 1% to 4% and magnetic field density(MFD) from 0.002 to 0.008 T,HTR and subsequently TPF improved.The best result was observed for MSIFFS equipped with a trapezoidal-shaped turbulator with 4% Al_(2)O_(3) in the presence of IMF(B=0.008 T).The TPF increased with the augmentation of Re,and the maximum value of it was 5.2366 for MSIFFS equipped with a trapezoidal-shaped turbulator with 4% Al_(2)O_(3),B=0.008 T,and Re=10000.
基金Project(21271188) supported by the National Natural Science Foundation of China
文摘A Ti interlayer with thickness about 300 nm was sputtered on Cu microchannels, followed by an ultrasonic seeding with nanodiamond powders. Adherent diamond film with crystalline grains close to thermal equilibrium shape was tightly deposited by hot-filament chemical vapor deposition(HF-CVD). The nucleation and growth of diamond were investigated with micro-Raman spectroscope and field emission scanning electron microscope(FE-SEM) with energy dispersive X-ray detector(EDX). Results show that the nucleation density is found to be up to 1010 cm-2. The enhancement of the nucleation kinetics can be attributed to the nanometer rough Ti interlayer surface. An improved absorption of nanodiamond particles is found, which act as starting points for the diamond nucleation during HF-CVD process. Furthermore, finite element simulation was conducted to understand the thermal management properties of prepared diamond/Cu microchannel heat sink.
