This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
A novel method to manipulate or fabricate aspherical micro lens from photo curable polymer is pro... more A novel method to manipulate or fabricate aspherical micro lens from photo curable polymer is proposed in this paper. Two dimensional forces, carried out by electro-wetting and electrostatic forces were applied to shape polymer liquid from hemisphere into paraboloid or near cone shape. As a result, the Strehl ratio for this lens can be varied from 0.0076 in spherical shape into 0.8362 in near paraboloid shape, suitable for optical applications desiring lenses with high numerical apertures and resolution.
Articular cartilage in synovial joints such as the knee has limited capability to regenerate inde... more Articular cartilage in synovial joints such as the knee has limited capability to regenerate independently, and most clinical options for focal cartilage repair merely delay total joint replacement. Tissue engineering presents a repair strategy in which an injectable cell-laden scaffold material is used to reconstruct the joint in situ through mechanical stabilisation and cell-mediated regeneration. In this study, we designed and 3D-printed millimetre-scale micro-patterned PEGDA biomaterial microscaffolds which self-assemble through tessellation at a scale relevant for applications in osteochondral cartilage reconstruction. Using simulated chondral lesions in an in vitro model, a series of scaffold designs and viscous delivery solutions were assessed. Hexagonal microscaffolds (750 μm x 300 μm) demonstrated the best coverage of a model cartilage lesion (at 73.3%) when injected with a 1% methyl cellulose solution. When chondrocytes were introduced to the biomaterial via a collagen hyd...
Insufficient prognosis of local recurrence contributes to the poor progression-free survival rate... more Insufficient prognosis of local recurrence contributes to the poor progression-free survival rate and death in colorectal cancer (CRC) patients. Various biomarkers have been explored in predicting CRC recurrence. This study investigated the expressions of plasma/exosomal microRNA-21 (miR-21) in 113 CRC patients by qPCR, their values of predicting CRC recurrence, and the possibility to improve the prognostic efficacy in early CRC recurrence in stratified patients by combined biomarkers including circulating miR-21s, circulating tumour cells/microemboli (CTCs/CTM), and serum carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9). Expressions of plasma and exosomal miR-21s were significantly correlated (p < 0.0001) in all and late-stage patients, presenting similar correlations with other biomarkers. However, stage IV patients stratified by a high level of exosomal miR-21 and stage I to III patients stratified by a high level of plasma miR-21 displayed significantly worse...
The ability to deliver foreign molecules into a single living cell with high transfection efficie... more The ability to deliver foreign molecules into a single living cell with high transfection efficiency and high cell viability is of great interest in cell biology for applications in therapeutic development, diagnostics, and drug delivery towards personalized medicine. Various physical delivery methods have long demonstrated the ability to deliver cargo molecules directly to the cytoplasm or nucleus and the mechanisms underlying most of the approaches have been extensively investigated. However, most of these techniques are bulk approaches that are cell-specific and have low throughput delivery. In comparison to bulk measurements, single-cell measurement technologies can provide a better understanding of the interactions among molecules, organelles, cells, and the microenvironment, which can aid in the development of therapeutics and diagnostic tools. To elucidate distinct responses during cell genetic modification, methods to achieve transfection at the single-cell level are of grea...
The brain is an intricate network with complex organizational principles facilitating a concerted... more The brain is an intricate network with complex organizational principles facilitating a concerted communication between single-neurons, distinct neuron populations, and remote brain areas. The communication, technically referred to as connectivity, between single-neurons, is the center of many investigations aimed at elucidating pathophysiology, anatomical differences, and structural and functional features. In comparison with bulk analysis, single-neuron analysis can provide precise information about neurons or even sub-neuron level electrophysiology, anatomical differences, pathophysiology, structural and functional features, in addition to their communications with other neurons, and can promote essential information to understand the brain and its activity. This review highlights various single-neuron models and their behaviors, followed by different analysis methods. Again, to elucidate cellular dynamics in terms of electrophysiology at the single-neuron level, we emphasize in ...
Tissue-specific microenvironmental factors contribute to the targeting preferences of metastatic ... more Tissue-specific microenvironmental factors contribute to the targeting preferences of metastatic cancers. However, the physical attributes of the premetastatic microenvironment are not yet fully characterized. In this research, we develop a transwell-based alginate hydrogel (TAH) model to study how permeability, stiffness, and roughness of a hanging alginate hydrogel regulate breast cancer cell homing. In this model, a layer of physically characterized alginate hydrogel is formed at the bottom of a transwell insert, which is placed into a matching culture well with an adherent monolayer of breast cancer cells. We found that breast cancer cells dissociate from the monolayer and home to the TAH for continual growth. The process is facilitated by the presence of rich serum in the upper chamber, the increased stiffness of the gel, as well as its surface roughness. This model is able to support the homing ability of MCF-7 and MDA-MB-231 cells drifting across the vertical distance in the ...
The investigation of human disease mechanisms is difficult due to the heterogeneity in gene expre... more The investigation of human disease mechanisms is difficult due to the heterogeneity in gene expression and the physiological state of cells in a given population. In comparison to bulk cell measurements, single-cell measurement technologies can provide a better understanding of the interactions among molecules, organelles, cells, and the microenvironment, which can aid in the development of therapeutics and diagnostic tools. In recent years, single-cell technologies have become increasingly robust and accessible, although limitations exist. In this review, we describe the recent advances in single-cell technologies and their applications in single-cell manipulation, diagnosis, and therapeutics development.
Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Detect... more Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Detecting and enumerating circulating tumor cells (CTCs) in patients with colorectal cancer emerged as an important prognostic tool which provides a direct estimate of metastatic potential. Improving the turnaround time and decreasing sample volume is critical for incorporating this liquid biopsy tool into routine practice. The objective of the current study was to validate the clinical feasibility of a self-assembled cell array (SACA) chip, a CTC counting platform with less than 4 h turnaround time, in patients with newly diagnosed colorectal cancers. In total, 179 patients with newly diagnosed colorectal cancers from a single institute were enrolled. Epithelial cell adhesion molecule positive (EpCAM(+)), cluster of differentiation 45 negative (CD45(−)) cells were isolated and enumerated from 2 mL of peripheral vein blood (PB) and inferior mesenteric vein blood (IMV) samples obtained during s...
Small (Weinheim an der Bergstrasse, Germany), Jan 16, 2018
The Zn stored in the secretory vesicles of glutamatergic neurons is coreleased with glutamate upo... more The Zn stored in the secretory vesicles of glutamatergic neurons is coreleased with glutamate upon stimulation, resulting in the elevation of extracellular Zn concentration (CZn2+ex). This elevation of CZn2+ex regulates the neurotransmission and facilitates the fibrilization of amyloid-β (Aβ). However, the exact CZn2+ex surrounding neurons under (patho)physiological conditions is not clear and the connection between CZn2+ex and the Aβ fibrilization remains obscure. Here, a silicon nanowire field-effect transistor (SiNW-FET) with the Zn -sensitive fluorophore, FluoZin-3 (FZ-3), to quantify the CZn2+ex in real time is modified. This FZ-3/SiNW-FET device has a dissociation constant of ≈12 × 10 m against Zn . By placing a coverslip seeded with cultured embryonic cortical neurons atop an FZ-3/SiNW-FET, the CZn2+ex elevated to ≈110 × 10 m upon stimulation with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Blockers against the AMPA receptor or exocytosis greatly suppress thi...
Proteins belonging to the toll-like receptor (TLR) family, particularly TLR2, are the major compo... more Proteins belonging to the toll-like receptor (TLR) family, particularly TLR2, are the major components of innate immunity against Leptospira infection. The ligands for TLR2 harbor several conserved patterns such as lipidation molecules, leucine-rich repeat (LRR) domains, TLR2 binding motifs, and TLR2 binding structure. In Leptospira, LipL32 interacts with TLR2 on human kidney cells concomitantly stimulating inflammatory responses. However, the binding mechanism of LipL32 to TLR2 is unknown. The computational prediction suggests that β1β2, loop-α3-loop, and α4 domains of LipL32 play vital roles in LipL32-TLR2 complex formation. To test these predictions, protein truncation experiments revealed that LipL32ΔNβ1β2 significantly decreased the affinity to TLR2 while LipL32ΔCα4 slightly reduced it. Interestingly, LipL32ΔCenα3 retained affinity to TLR2 in the absence of Ca2+ ions, indicating that Cenα3 play a role preventing the interaction between LipL32 and TLR2. Furthermore, the critical...
The concentration gradient of K(+) across the cell membrane of a neuron determines its resting po... more The concentration gradient of K(+) across the cell membrane of a neuron determines its resting potential and cell excitability. During neurotransmission, the efflux of K(+) from the cell via various channels will not only decrease the intracellular K(+) content but also elevate the extracellular K(+) concentration. However, it is not clear to what extent this change could be. In this study, we developed a multiple-parallel-connected silicon nanowire field-effect transistor (SiNW-FET) modified with K(+)-specific DNA-aptamers (aptamer/SiNW-FET) for the real-time detection of the K(+) efflux from cultured cortical neurons. The aptamer/SiNW-FET showed an association constant of (2.18 ± 0.44) × 10(6) M(-1) against K(+) and an either less or negligible response to other alkali metal ions. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) stimulation induced an outward current and hyperpolarized the membrane potential in a whole-cell patched neuron under a Na(+)/K(+)-free buf...
This paper presents a novel method for the attachment of a 1.8-nm Au nanoparticle (Au-NP) to the ... more This paper presents a novel method for the attachment of a 1.8-nm Au nanoparticle (Au-NP) to the tip of an atomic force microscopy (AFM) probe through the application of a current-limited bias voltage. The resulting probe is capable of picking up individual objects at the sub-4-nm scale. We also discuss the mechanisms involved in the attachment of the Au-NP to the very apex of an AFM probe tip. The Au-NP-modified AFM tips were used to pick up individual 4-nm quantum dots (QDs) using a chemically functionalized method. Single QD blinking was reduced considerably on the Au-NP-modified AFM tip. The resulting AFM tips present an excellent platform for the manipulation of single protein molecules in the study of single protein-protein interactions.
The behaviors of cell to cell or cell to environment with their organelles and their intracellula... more The behaviors of cell to cell or cell to environment with their organelles and their intracellular physical or biochemical effects are still not fully understood. Analyzing millions of cells together cannot provide detailed information, such as cell proliferation, differentiation or different responses to external stimuli and intracellular reaction. Thus, single cell level research is becoming a pioneering research area that unveils the interaction details in high temporal and spatial resolution among cells. To analyze the cellular function, single cell electroporation can be conducted by employing a miniaturized device, whose dimension should be similar to that of a single cell. Micro/nanofluidic devices can fulfill this requirement for single cell electroporation. This device is not only useful for cell lysis, cell to cell fusion or separation, insertion of drug, DNA and antibodies inside single cell, but also it can control biochemical, electrical and mechanical parameters using electroporation technique. This device provides better performance such as high transfection efficiency, high cell viability, lower Joule heating effect, less sample contamination, lower toxicity during electroporation experiment when compared to bulk electroporation process. In addition, single organelles within a cell can be analyzed selectively by reducing the electrode size and gap at nanoscale level. This advanced technique can deliver (in/out) biomolecules precisely through a small membrane area (micro to nanoscale area) of the single cell, known as localized single cell membrane electroporation (LSCMEP). These articles emphasize the recent progress in micro/nanofluidic single cell electroporation, which is potentially beneficial for
This paper introduces a simple, yet controllable scheme to pick up a single 13 nm Au nanoparticle... more This paper introduces a simple, yet controllable scheme to pick up a single 13 nm Au nanoparticle (Au-NP) using the tip of an atomic force microscope (AFM) probe through the application of electrical biases between the tip and the Au-NP. Transmission electron microscope (TEM) images were acquired to verify that a single Au-NP was attached to the AFM probe. We postulate that the mechanism underlying the ability to manipulate individual Au-NPs at the apex of the AFM probe tip is Coulomb interaction induced by tip bias. The AFM tip with the attached Au-NP was then used to study the interaction between a single quantum dot (QD) and the Au-NP. The blinking behavior of single colloidal CdSe/ZnS core/ shell QD was significantly suppressed with the approach of the 13 nm Au-NP attached to the AFM tip.
This study reports that the success of reservoir-®lling strongly depends on the designs of the hy... more This study reports that the success of reservoir-®lling strongly depends on the designs of the hydrophilic wall surface and the well shape/ size of the¯ow network. The idea is illustrated both by experiments and numerical simulations: micro-particle-image-velocimetry (m-PIV) system is setup to monitor the process of a liquid slug moving in and out of the micro-reservoir and numerical computations are performed by solving ®rst principle equations to provide the details of the¯ow process. The cross-check between measurements and computations validate the computations. Numerical computations solve conservation equations similar to homogenous¯ow model used in two phase¯ow calculation in cooperation with volume-of-¯uid (VOF) interface tracking methodology and continuum surface force (CSF) model. The simulations show that wall surface property as hydrophilic/hydrophobic is a dominating factor in ®lling processes of reservoirs of various shapes. A¯ow system consisting of micro-channels and micro-wells is fabricated using MEMS technology to demonstrate the ®lling process and validate numerical simulation. The agreement between measurement and computation helps to fully understand the process.
In the past two decades, Micro Fluidic Systems (MFS) have emerged as a powerful tool for biosensi... more In the past two decades, Micro Fluidic Systems (MFS) have emerged as a powerful tool for biosensing, particularly in enriching and purifying molecules and cells in biological samples. Compared with conventional sensing techniques, distinctive advantages of using MFS for biomedicine include ultra-high sensitivity, higher throughput, in-situ monitoring and lower cost. This review aims to summarize the recent advancements in two major types of micro fluidic systems, continuous and discrete MFS, as well as their biomedical applications. The state-of-the-art of active and passive mechanisms of fluid manipulation for mixing, separation, purification and concentration will also be elaborated. Future trends of using MFS in detection at molecular or cellular level, especially in stem cell therapy, tissue engineering and regenerative medicine, are also prospected.
We study the indentation of a free-standing lipid membrane suspended over a nanopore on a hydroph... more We study the indentation of a free-standing lipid membrane suspended over a nanopore on a hydrophobic substrate by means of molecular dynamics simulations. We find that in the course of indentation, the membrane bends at the point of contact, and the fringes of the membrane glide downward intermittently along the pore edges and stop gliding when the fringes reach the edge bottoms. The bending continues afterwards, and the large strain eventually induces a phase transition in the membrane, transformed from a bilayered structure to an interdigitated structure. The membrane is finally ruptured when the indentation goes deep enough. Several local physical quantities in the pore regions are calculated, which include the tilt angle of lipid molecules, the nematic order, the included angle and the distance between neighboring lipids. The variations of these quantities reveal many detailed, not-yet-specified local structural transitions of lipid molecules under indentation. The force-indentation curve is also studied and discussed. The results make connection between the microscopic structure and the macroscopic properties, and provide deep insight in the understanding of the stability of a lipid membrane spanning over a nanopore.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
A novel method to manipulate or fabricate aspherical micro lens from photo curable polymer is pro... more A novel method to manipulate or fabricate aspherical micro lens from photo curable polymer is proposed in this paper. Two dimensional forces, carried out by electro-wetting and electrostatic forces were applied to shape polymer liquid from hemisphere into paraboloid or near cone shape. As a result, the Strehl ratio for this lens can be varied from 0.0076 in spherical shape into 0.8362 in near paraboloid shape, suitable for optical applications desiring lenses with high numerical apertures and resolution.
Articular cartilage in synovial joints such as the knee has limited capability to regenerate inde... more Articular cartilage in synovial joints such as the knee has limited capability to regenerate independently, and most clinical options for focal cartilage repair merely delay total joint replacement. Tissue engineering presents a repair strategy in which an injectable cell-laden scaffold material is used to reconstruct the joint in situ through mechanical stabilisation and cell-mediated regeneration. In this study, we designed and 3D-printed millimetre-scale micro-patterned PEGDA biomaterial microscaffolds which self-assemble through tessellation at a scale relevant for applications in osteochondral cartilage reconstruction. Using simulated chondral lesions in an in vitro model, a series of scaffold designs and viscous delivery solutions were assessed. Hexagonal microscaffolds (750 μm x 300 μm) demonstrated the best coverage of a model cartilage lesion (at 73.3%) when injected with a 1% methyl cellulose solution. When chondrocytes were introduced to the biomaterial via a collagen hyd...
Insufficient prognosis of local recurrence contributes to the poor progression-free survival rate... more Insufficient prognosis of local recurrence contributes to the poor progression-free survival rate and death in colorectal cancer (CRC) patients. Various biomarkers have been explored in predicting CRC recurrence. This study investigated the expressions of plasma/exosomal microRNA-21 (miR-21) in 113 CRC patients by qPCR, their values of predicting CRC recurrence, and the possibility to improve the prognostic efficacy in early CRC recurrence in stratified patients by combined biomarkers including circulating miR-21s, circulating tumour cells/microemboli (CTCs/CTM), and serum carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9). Expressions of plasma and exosomal miR-21s were significantly correlated (p < 0.0001) in all and late-stage patients, presenting similar correlations with other biomarkers. However, stage IV patients stratified by a high level of exosomal miR-21 and stage I to III patients stratified by a high level of plasma miR-21 displayed significantly worse...
The ability to deliver foreign molecules into a single living cell with high transfection efficie... more The ability to deliver foreign molecules into a single living cell with high transfection efficiency and high cell viability is of great interest in cell biology for applications in therapeutic development, diagnostics, and drug delivery towards personalized medicine. Various physical delivery methods have long demonstrated the ability to deliver cargo molecules directly to the cytoplasm or nucleus and the mechanisms underlying most of the approaches have been extensively investigated. However, most of these techniques are bulk approaches that are cell-specific and have low throughput delivery. In comparison to bulk measurements, single-cell measurement technologies can provide a better understanding of the interactions among molecules, organelles, cells, and the microenvironment, which can aid in the development of therapeutics and diagnostic tools. To elucidate distinct responses during cell genetic modification, methods to achieve transfection at the single-cell level are of grea...
The brain is an intricate network with complex organizational principles facilitating a concerted... more The brain is an intricate network with complex organizational principles facilitating a concerted communication between single-neurons, distinct neuron populations, and remote brain areas. The communication, technically referred to as connectivity, between single-neurons, is the center of many investigations aimed at elucidating pathophysiology, anatomical differences, and structural and functional features. In comparison with bulk analysis, single-neuron analysis can provide precise information about neurons or even sub-neuron level electrophysiology, anatomical differences, pathophysiology, structural and functional features, in addition to their communications with other neurons, and can promote essential information to understand the brain and its activity. This review highlights various single-neuron models and their behaviors, followed by different analysis methods. Again, to elucidate cellular dynamics in terms of electrophysiology at the single-neuron level, we emphasize in ...
Tissue-specific microenvironmental factors contribute to the targeting preferences of metastatic ... more Tissue-specific microenvironmental factors contribute to the targeting preferences of metastatic cancers. However, the physical attributes of the premetastatic microenvironment are not yet fully characterized. In this research, we develop a transwell-based alginate hydrogel (TAH) model to study how permeability, stiffness, and roughness of a hanging alginate hydrogel regulate breast cancer cell homing. In this model, a layer of physically characterized alginate hydrogel is formed at the bottom of a transwell insert, which is placed into a matching culture well with an adherent monolayer of breast cancer cells. We found that breast cancer cells dissociate from the monolayer and home to the TAH for continual growth. The process is facilitated by the presence of rich serum in the upper chamber, the increased stiffness of the gel, as well as its surface roughness. This model is able to support the homing ability of MCF-7 and MDA-MB-231 cells drifting across the vertical distance in the ...
The investigation of human disease mechanisms is difficult due to the heterogeneity in gene expre... more The investigation of human disease mechanisms is difficult due to the heterogeneity in gene expression and the physiological state of cells in a given population. In comparison to bulk cell measurements, single-cell measurement technologies can provide a better understanding of the interactions among molecules, organelles, cells, and the microenvironment, which can aid in the development of therapeutics and diagnostic tools. In recent years, single-cell technologies have become increasingly robust and accessible, although limitations exist. In this review, we describe the recent advances in single-cell technologies and their applications in single-cell manipulation, diagnosis, and therapeutics development.
Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Detect... more Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Detecting and enumerating circulating tumor cells (CTCs) in patients with colorectal cancer emerged as an important prognostic tool which provides a direct estimate of metastatic potential. Improving the turnaround time and decreasing sample volume is critical for incorporating this liquid biopsy tool into routine practice. The objective of the current study was to validate the clinical feasibility of a self-assembled cell array (SACA) chip, a CTC counting platform with less than 4 h turnaround time, in patients with newly diagnosed colorectal cancers. In total, 179 patients with newly diagnosed colorectal cancers from a single institute were enrolled. Epithelial cell adhesion molecule positive (EpCAM(+)), cluster of differentiation 45 negative (CD45(−)) cells were isolated and enumerated from 2 mL of peripheral vein blood (PB) and inferior mesenteric vein blood (IMV) samples obtained during s...
Small (Weinheim an der Bergstrasse, Germany), Jan 16, 2018
The Zn stored in the secretory vesicles of glutamatergic neurons is coreleased with glutamate upo... more The Zn stored in the secretory vesicles of glutamatergic neurons is coreleased with glutamate upon stimulation, resulting in the elevation of extracellular Zn concentration (CZn2+ex). This elevation of CZn2+ex regulates the neurotransmission and facilitates the fibrilization of amyloid-β (Aβ). However, the exact CZn2+ex surrounding neurons under (patho)physiological conditions is not clear and the connection between CZn2+ex and the Aβ fibrilization remains obscure. Here, a silicon nanowire field-effect transistor (SiNW-FET) with the Zn -sensitive fluorophore, FluoZin-3 (FZ-3), to quantify the CZn2+ex in real time is modified. This FZ-3/SiNW-FET device has a dissociation constant of ≈12 × 10 m against Zn . By placing a coverslip seeded with cultured embryonic cortical neurons atop an FZ-3/SiNW-FET, the CZn2+ex elevated to ≈110 × 10 m upon stimulation with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Blockers against the AMPA receptor or exocytosis greatly suppress thi...
Proteins belonging to the toll-like receptor (TLR) family, particularly TLR2, are the major compo... more Proteins belonging to the toll-like receptor (TLR) family, particularly TLR2, are the major components of innate immunity against Leptospira infection. The ligands for TLR2 harbor several conserved patterns such as lipidation molecules, leucine-rich repeat (LRR) domains, TLR2 binding motifs, and TLR2 binding structure. In Leptospira, LipL32 interacts with TLR2 on human kidney cells concomitantly stimulating inflammatory responses. However, the binding mechanism of LipL32 to TLR2 is unknown. The computational prediction suggests that β1β2, loop-α3-loop, and α4 domains of LipL32 play vital roles in LipL32-TLR2 complex formation. To test these predictions, protein truncation experiments revealed that LipL32ΔNβ1β2 significantly decreased the affinity to TLR2 while LipL32ΔCα4 slightly reduced it. Interestingly, LipL32ΔCenα3 retained affinity to TLR2 in the absence of Ca2+ ions, indicating that Cenα3 play a role preventing the interaction between LipL32 and TLR2. Furthermore, the critical...
The concentration gradient of K(+) across the cell membrane of a neuron determines its resting po... more The concentration gradient of K(+) across the cell membrane of a neuron determines its resting potential and cell excitability. During neurotransmission, the efflux of K(+) from the cell via various channels will not only decrease the intracellular K(+) content but also elevate the extracellular K(+) concentration. However, it is not clear to what extent this change could be. In this study, we developed a multiple-parallel-connected silicon nanowire field-effect transistor (SiNW-FET) modified with K(+)-specific DNA-aptamers (aptamer/SiNW-FET) for the real-time detection of the K(+) efflux from cultured cortical neurons. The aptamer/SiNW-FET showed an association constant of (2.18 ± 0.44) × 10(6) M(-1) against K(+) and an either less or negligible response to other alkali metal ions. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) stimulation induced an outward current and hyperpolarized the membrane potential in a whole-cell patched neuron under a Na(+)/K(+)-free buf...
This paper presents a novel method for the attachment of a 1.8-nm Au nanoparticle (Au-NP) to the ... more This paper presents a novel method for the attachment of a 1.8-nm Au nanoparticle (Au-NP) to the tip of an atomic force microscopy (AFM) probe through the application of a current-limited bias voltage. The resulting probe is capable of picking up individual objects at the sub-4-nm scale. We also discuss the mechanisms involved in the attachment of the Au-NP to the very apex of an AFM probe tip. The Au-NP-modified AFM tips were used to pick up individual 4-nm quantum dots (QDs) using a chemically functionalized method. Single QD blinking was reduced considerably on the Au-NP-modified AFM tip. The resulting AFM tips present an excellent platform for the manipulation of single protein molecules in the study of single protein-protein interactions.
The behaviors of cell to cell or cell to environment with their organelles and their intracellula... more The behaviors of cell to cell or cell to environment with their organelles and their intracellular physical or biochemical effects are still not fully understood. Analyzing millions of cells together cannot provide detailed information, such as cell proliferation, differentiation or different responses to external stimuli and intracellular reaction. Thus, single cell level research is becoming a pioneering research area that unveils the interaction details in high temporal and spatial resolution among cells. To analyze the cellular function, single cell electroporation can be conducted by employing a miniaturized device, whose dimension should be similar to that of a single cell. Micro/nanofluidic devices can fulfill this requirement for single cell electroporation. This device is not only useful for cell lysis, cell to cell fusion or separation, insertion of drug, DNA and antibodies inside single cell, but also it can control biochemical, electrical and mechanical parameters using electroporation technique. This device provides better performance such as high transfection efficiency, high cell viability, lower Joule heating effect, less sample contamination, lower toxicity during electroporation experiment when compared to bulk electroporation process. In addition, single organelles within a cell can be analyzed selectively by reducing the electrode size and gap at nanoscale level. This advanced technique can deliver (in/out) biomolecules precisely through a small membrane area (micro to nanoscale area) of the single cell, known as localized single cell membrane electroporation (LSCMEP). These articles emphasize the recent progress in micro/nanofluidic single cell electroporation, which is potentially beneficial for
This paper introduces a simple, yet controllable scheme to pick up a single 13 nm Au nanoparticle... more This paper introduces a simple, yet controllable scheme to pick up a single 13 nm Au nanoparticle (Au-NP) using the tip of an atomic force microscope (AFM) probe through the application of electrical biases between the tip and the Au-NP. Transmission electron microscope (TEM) images were acquired to verify that a single Au-NP was attached to the AFM probe. We postulate that the mechanism underlying the ability to manipulate individual Au-NPs at the apex of the AFM probe tip is Coulomb interaction induced by tip bias. The AFM tip with the attached Au-NP was then used to study the interaction between a single quantum dot (QD) and the Au-NP. The blinking behavior of single colloidal CdSe/ZnS core/ shell QD was significantly suppressed with the approach of the 13 nm Au-NP attached to the AFM tip.
This study reports that the success of reservoir-®lling strongly depends on the designs of the hy... more This study reports that the success of reservoir-®lling strongly depends on the designs of the hydrophilic wall surface and the well shape/ size of the¯ow network. The idea is illustrated both by experiments and numerical simulations: micro-particle-image-velocimetry (m-PIV) system is setup to monitor the process of a liquid slug moving in and out of the micro-reservoir and numerical computations are performed by solving ®rst principle equations to provide the details of the¯ow process. The cross-check between measurements and computations validate the computations. Numerical computations solve conservation equations similar to homogenous¯ow model used in two phase¯ow calculation in cooperation with volume-of-¯uid (VOF) interface tracking methodology and continuum surface force (CSF) model. The simulations show that wall surface property as hydrophilic/hydrophobic is a dominating factor in ®lling processes of reservoirs of various shapes. A¯ow system consisting of micro-channels and micro-wells is fabricated using MEMS technology to demonstrate the ®lling process and validate numerical simulation. The agreement between measurement and computation helps to fully understand the process.
In the past two decades, Micro Fluidic Systems (MFS) have emerged as a powerful tool for biosensi... more In the past two decades, Micro Fluidic Systems (MFS) have emerged as a powerful tool for biosensing, particularly in enriching and purifying molecules and cells in biological samples. Compared with conventional sensing techniques, distinctive advantages of using MFS for biomedicine include ultra-high sensitivity, higher throughput, in-situ monitoring and lower cost. This review aims to summarize the recent advancements in two major types of micro fluidic systems, continuous and discrete MFS, as well as their biomedical applications. The state-of-the-art of active and passive mechanisms of fluid manipulation for mixing, separation, purification and concentration will also be elaborated. Future trends of using MFS in detection at molecular or cellular level, especially in stem cell therapy, tissue engineering and regenerative medicine, are also prospected.
We study the indentation of a free-standing lipid membrane suspended over a nanopore on a hydroph... more We study the indentation of a free-standing lipid membrane suspended over a nanopore on a hydrophobic substrate by means of molecular dynamics simulations. We find that in the course of indentation, the membrane bends at the point of contact, and the fringes of the membrane glide downward intermittently along the pore edges and stop gliding when the fringes reach the edge bottoms. The bending continues afterwards, and the large strain eventually induces a phase transition in the membrane, transformed from a bilayered structure to an interdigitated structure. The membrane is finally ruptured when the indentation goes deep enough. Several local physical quantities in the pore regions are calculated, which include the tilt angle of lipid molecules, the nematic order, the included angle and the distance between neighboring lipids. The variations of these quantities reveal many detailed, not-yet-specified local structural transitions of lipid molecules under indentation. The force-indentation curve is also studied and discussed. The results make connection between the microscopic structure and the macroscopic properties, and provide deep insight in the understanding of the stability of a lipid membrane spanning over a nanopore.
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