Highlights Cell spheroids are spherical aggregates best mimicking the tissue microenvironment. ... more Highlights Cell spheroids are spherical aggregates best mimicking the tissue microenvironment. Spheroid culture better recapitulates the in-vivo condition in microfluidic chips. Microfluidics provides rapid spheroid formation with size uniformity and control. These chips contain microwells, microstructures, droplet generators, etc. To fabricate such chips, some design considerations must be taken into account.
Thin porous membranes are important components in a microfluidic device, serving as separators, f... more Thin porous membranes are important components in a microfluidic device, serving as separators, filters, and scaffolds for cell culture. However, the fabrication and the integration of these membranes possess many challenges, which restrict their widespread applications. This paper reports a facile technique to fabricate robust membrane-embedded microfluidic devices. We integrated an electrospun membrane into a polydimethylsiloxane (PDMS) device using the simple plasma-activated bonding technique. To increase the flexibility of the membrane and to address the leakage problem, the electrospun membrane was fabricated with the highest weight ratio of PDMS to polymethylmethacrylate (i.e., 6:1 w/w). The membrane-integrated microfluidic device could withstand a flow rate of up to 50 l/min. As a proof of concept, we demonstrated that such a compartmentalized microfluidic platform could be successfully used for cell culture with the capability of providing a more realistic -like condition. ...
Drug delivery and translational research, Jan 21, 2017
Micro and nanotechnology can potentially revolutionize drug delivery systems. Novel microfluidic ... more Micro and nanotechnology can potentially revolutionize drug delivery systems. Novel microfluidic systems have been employed for the cell culture applications and drug delivery by micro and nanocarriers. Cells in the microchannels are under static and dynamic flow perfusion of culture media that provides nutrition and removes waste from the cells. This exerts hydrostatic and hydrodynamic forces on the cells. These forces can considerably affect the functions of the living cells. In this paper, we simulated the flow of air, culture medium, and the particle transport and deposition in the microchannels under different angles of connection inlet. It was found that the shear stress induced by the medium culture flow is not so high to damage the cells and that it is roughly uniform in the cell culture section (CCS). However, the local shear stresses in the other parts of the microchip differ by changing the angles of the connection inlet. The results showed that the particle deposition wa...
This paper reports the fabrication of electrospun polydimethylsiloxane (PDMS) membranes/scaffolds... more This paper reports the fabrication of electrospun polydimethylsiloxane (PDMS) membranes/scaffolds that are suitable for three-dimensional (3D) cell culture. Through modification the ratio between PDMS and polymethylmethacrylate (PMMA) as carrier polymer, we report the possibility of increasing PDMS weight ratio of up to 6 for electrospinning. Increasing the PDMS content increases the fiber diameter, the pore size, and the hydrophobicity. To our best knowledge, this is the first report describing beads-free, durable and portable electrospun membrane with maximum content of PDMS suitable for cell culture applications. To show the proof-of-concept, we successfully cultured epithelial lung cancer cells on these membranes in a static well plate without surface modification. Surprisingly, due to three-dimensional (3D) and hydrophobic nature of the electrospun fibers, cells aggregated into 3D multicellular spheroids. These easily detachable and cost-effective scaffolds with controllable th...
With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death w... more With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system) make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D) nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate the efficacy of anticancer drugs are integrated on the same chip. In this article, we critically review the cutting edge advances in this field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1) Lung; (2) Bone marrow; (3) Brain; (4) Breast; (5) Urinary system (kidney, bladder and prostate); (6) Intestine; and (7) Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heart-liver-intestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET) of anticancer drugs and more realistically recapitulate tumor in vivo-like microenvironment.
Three dimensional computational models of both sides of human nasal passages were developed to in... more Three dimensional computational models of both sides of human nasal passages were developed to investigate the effect of septal deviation on the flow patterns and deposition of micro/nano-particles in the realistic human nasal airways before and after septoplasty. A series of coronal CT scan images from a live 25-year old nonsmoking male with septal deviation in his right nasal passage was used to construct the model. For low to moderate activities, the steady airflows through the nasal passages were simulated. Eulerian and Lagrangian approaches were used, respectively, for nano- and micro-particles. The results show that the flow field and particle deposition strongly depend on the passage geometry especially for micro particles. In particular, the deposition rate in the passage with septal deviation was much higher compared with those in the normal (left) passage and the postoperative passage. Despite the similarity of total micro-particle deposition in the postoperative and the normal cavities, the regional deposition patterns were quite different in these passages. The deposition of nano-particles, however, showed similar trends in the postoperative right nasal passage and the normal left passage. The simulation results showed that in addition to the major alteration of the airflow pattern after the septoplasty operation, there are significant changes in the deposition pattern of nano- and micro-particles. Despite the anatomical differences between the available experimental configuration and the present computer model, the simulation results for the deposition efficiency of particles of different sizes are in qualitative agreement with the available data.
Highlights Cell spheroids are spherical aggregates best mimicking the tissue microenvironment. ... more Highlights Cell spheroids are spherical aggregates best mimicking the tissue microenvironment. Spheroid culture better recapitulates the in-vivo condition in microfluidic chips. Microfluidics provides rapid spheroid formation with size uniformity and control. These chips contain microwells, microstructures, droplet generators, etc. To fabricate such chips, some design considerations must be taken into account.
Thin porous membranes are important components in a microfluidic device, serving as separators, f... more Thin porous membranes are important components in a microfluidic device, serving as separators, filters, and scaffolds for cell culture. However, the fabrication and the integration of these membranes possess many challenges, which restrict their widespread applications. This paper reports a facile technique to fabricate robust membrane-embedded microfluidic devices. We integrated an electrospun membrane into a polydimethylsiloxane (PDMS) device using the simple plasma-activated bonding technique. To increase the flexibility of the membrane and to address the leakage problem, the electrospun membrane was fabricated with the highest weight ratio of PDMS to polymethylmethacrylate (i.e., 6:1 w/w). The membrane-integrated microfluidic device could withstand a flow rate of up to 50 l/min. As a proof of concept, we demonstrated that such a compartmentalized microfluidic platform could be successfully used for cell culture with the capability of providing a more realistic -like condition. ...
Drug delivery and translational research, Jan 21, 2017
Micro and nanotechnology can potentially revolutionize drug delivery systems. Novel microfluidic ... more Micro and nanotechnology can potentially revolutionize drug delivery systems. Novel microfluidic systems have been employed for the cell culture applications and drug delivery by micro and nanocarriers. Cells in the microchannels are under static and dynamic flow perfusion of culture media that provides nutrition and removes waste from the cells. This exerts hydrostatic and hydrodynamic forces on the cells. These forces can considerably affect the functions of the living cells. In this paper, we simulated the flow of air, culture medium, and the particle transport and deposition in the microchannels under different angles of connection inlet. It was found that the shear stress induced by the medium culture flow is not so high to damage the cells and that it is roughly uniform in the cell culture section (CCS). However, the local shear stresses in the other parts of the microchip differ by changing the angles of the connection inlet. The results showed that the particle deposition wa...
This paper reports the fabrication of electrospun polydimethylsiloxane (PDMS) membranes/scaffolds... more This paper reports the fabrication of electrospun polydimethylsiloxane (PDMS) membranes/scaffolds that are suitable for three-dimensional (3D) cell culture. Through modification the ratio between PDMS and polymethylmethacrylate (PMMA) as carrier polymer, we report the possibility of increasing PDMS weight ratio of up to 6 for electrospinning. Increasing the PDMS content increases the fiber diameter, the pore size, and the hydrophobicity. To our best knowledge, this is the first report describing beads-free, durable and portable electrospun membrane with maximum content of PDMS suitable for cell culture applications. To show the proof-of-concept, we successfully cultured epithelial lung cancer cells on these membranes in a static well plate without surface modification. Surprisingly, due to three-dimensional (3D) and hydrophobic nature of the electrospun fibers, cells aggregated into 3D multicellular spheroids. These easily detachable and cost-effective scaffolds with controllable th...
With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death w... more With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system) make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D) nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate the efficacy of anticancer drugs are integrated on the same chip. In this article, we critically review the cutting edge advances in this field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1) Lung; (2) Bone marrow; (3) Brain; (4) Breast; (5) Urinary system (kidney, bladder and prostate); (6) Intestine; and (7) Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heart-liver-intestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET) of anticancer drugs and more realistically recapitulate tumor in vivo-like microenvironment.
Three dimensional computational models of both sides of human nasal passages were developed to in... more Three dimensional computational models of both sides of human nasal passages were developed to investigate the effect of septal deviation on the flow patterns and deposition of micro/nano-particles in the realistic human nasal airways before and after septoplasty. A series of coronal CT scan images from a live 25-year old nonsmoking male with septal deviation in his right nasal passage was used to construct the model. For low to moderate activities, the steady airflows through the nasal passages were simulated. Eulerian and Lagrangian approaches were used, respectively, for nano- and micro-particles. The results show that the flow field and particle deposition strongly depend on the passage geometry especially for micro particles. In particular, the deposition rate in the passage with septal deviation was much higher compared with those in the normal (left) passage and the postoperative passage. Despite the similarity of total micro-particle deposition in the postoperative and the normal cavities, the regional deposition patterns were quite different in these passages. The deposition of nano-particles, however, showed similar trends in the postoperative right nasal passage and the normal left passage. The simulation results showed that in addition to the major alteration of the airflow pattern after the septoplasty operation, there are significant changes in the deposition pattern of nano- and micro-particles. Despite the anatomical differences between the available experimental configuration and the present computer model, the simulation results for the deposition efficiency of particles of different sizes are in qualitative agreement with the available data.
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