Journal: Lab on a chip

Article Title: 3D Microfluidic Ex Vivo Culture of Organotypic Tumor Spheroids to Model Immune Checkpoint Blockade

doi: 10.1039/c8lc00322j

Figure Lengend Snippet: (A), the 3D cell culture chip (AIM Biotech) is shown with three independent microfluidic chambers per chip. Red rectangle identifies a single microfluidic chamber in the 3D cell culture chip. (B-C), each device contains a center gel region with posts separating the gel region from the anti-parallel side channels. Gel loading port and media ports labeled (B), along with center and side channels (C).

Article Snippet: Media channels were designed including larger reservoirs to prevent over-aspiration ( ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 – caption a7 caption a8 Microfluidic device. ( A ), the 3D cell culture chip (AIM Biotech) is shown with three independent microfluidic chambers per chip.

Techniques: Cell Culture, Labeling

Journal: Lab on a chip

Article Title: 3D Microfluidic Ex Vivo Culture of Organotypic Tumor Spheroids to Model Immune Checkpoint Blockade

doi: 10.1039/c8lc00322j

Figure Lengend Snippet: (A), acridine orange (AO) and propidium iodide (PI) staining of MC38 MDOTS on Day 6 of ex vivo culture, comparing control (isotype control IgG, 10 μg/mL) with anti-PD-1 (10 μg/mL). B, AO/PI and Hoechst/PI staining of CT26 MDOTS on Day 5 of ex vivo culture, comparing control (isotype control IgG, 10 μg/mL) with anti-PD-1 (10 μg/mL). C-D, Live/Dead analysis (C) and fluorescence images (D) of CT26 MDOTS treated with IgG or anti-PD-1 (10 μg/mL) for 5 days in 3D microfluidic culture (“3D”) compared to 384-well plates (“2D”) (3D - Ho/PI; 2D - AO/PI) (****p<0.0001, ns = not significant; Kruskal-Wallis with multiple comparisons; n≥3). Scale bars indicate 200 μm (A, B, D).

Article Snippet: Media channels were designed including larger reservoirs to prevent over-aspiration ( ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 – caption a7 caption a8 Microfluidic device. ( A ), the 3D cell culture chip (AIM Biotech) is shown with three independent microfluidic chambers per chip.

Techniques: Staining, Ex Vivo, Control, Fluorescence

Journal: Lab on a chip

Article Title: 3D Microfluidic Ex Vivo Culture of Organotypic Tumor Spheroids to Model Immune Checkpoint Blockade

doi: 10.1039/c8lc00322j

Figure Lengend Snippet: Summary of the advantages/limitations of MDOTS/PDOTS microfluidic culture models relative to other in vivo and in vitro cancer models. Several typical references are provided for each type of culture.

Article Snippet: Media channels were designed including larger reservoirs to prevent over-aspiration ( ). fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 3 – caption a7 caption a8 Microfluidic device. ( A ), the 3D cell culture chip (AIM Biotech) is shown with three independent microfluidic chambers per chip.

Techniques: In Vivo, In Vitro, Ex Vivo, Cell Culture, Imaging, Migration, FACS, High Throughput Screening Assay, Chemotaxis Assay, Permeability, Membrane, Isolation, Derivative Assay

Journal: Lab on a chip

Article Title: Miniaturized Devices for Point of Care Molecular Detection of HIV

doi: 10.1039/c6lc01239f

Figure Lengend Snippet: Microfluidic-based nucleic acid extraction of HIV. (A) A multifunctional amplification reactor chip integrated with a nucleic acid isolation membrane for HIV virus detection in saliva. Top inset is a side view of the multifunctional amplification reactor with a flow-through isolation membrane. Reproduced with permission from ref. 55. Copyright 2011 Royal Society of Chemistry. (B) Top: schematic of the immiscible phase filter for wash-free nucleic acid extraction. Bottom: Photograph of immiscible phase filter-based cartridge containing lysis/binding buffer, elution buffer, and a red colored liquid wax. Reproduced with permission from ref. 56. Copyright 2010 Elsevier. (C) Photograph of wax-based IFAST device for nucleic acid extraction. Reproduced with permission from ref. 57. Copyright 2014 Elsevier. (D) A schematic of AirJump operation for high throughput nucleic acid extraction: (1) an elution plate is placed above a sample plate loaded with PMPs. (2) Upon application of a magnet, PMPs-bound nucleic acids “jump” across the air gap and are deposited in the elution plate. Reproduced with permission from ref. 58. Copyright 2016 American Chemical Society.

Article Snippet: The integration of low-cost, microfluidic diagnostic chips with ubiquitous mobile phones to perform HIV diagnostics can greatly improve health monitoring in resource poor settings. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window caption a7 Integrated “sample-to-result” microfluidic devices for molecular diagnosis of HIV. (A) Photograph of the dual-path microfluidic device (Rheonix CARDTM) capable of simultaneously detecting anti-HIV antibody and HIV RNA.

Techniques: Extraction, Amplification, Isolation, Membrane, Virus, Lysis, Binding Assay, High Throughput Screening Assay

Journal: Lab on a chip

Article Title: Miniaturized Devices for Point of Care Molecular Detection of HIV

doi: 10.1039/c6lc01239f

Figure Lengend Snippet: Integrated “sample-to-result” microfluidic devices for molecular diagnosis of HIV. (A) Photograph of the dual-path microfluidic device (Rheonix CARD™) capable of simultaneously detecting anti-HIV antibody and HIV RNA. Reproduced with permission from ref. 22. Copyright 2013 hindawi. (B) Photograph of an integrated nucleic acid PCR cassette containing pre-stored reagents. For better visibility, the various food dyes in pouches represent different pre-stored liquid buffers. Reproduced with permission from ref. 23. Copyright 2010 Springer.

Article Snippet: The integration of low-cost, microfluidic diagnostic chips with ubiquitous mobile phones to perform HIV diagnostics can greatly improve health monitoring in resource poor settings. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window caption a7 Integrated “sample-to-result” microfluidic devices for molecular diagnosis of HIV. (A) Photograph of the dual-path microfluidic device (Rheonix CARDTM) capable of simultaneously detecting anti-HIV antibody and HIV RNA.

Techniques: Biomarker Discovery

Journal: Analytical and bioanalytical chemistry

Article Title: Microfluidic systems for studying dynamic function of adipocytes and adipose tissue

doi: 10.1007/s00216-017-0741-8

Figure Lengend Snippet: Recent examples of microfluidic systems for studying dynamic function of adipocytes and adipose tissue. (A) Schematic of microfluidic device for 3T3-L1 adipocyte stimulation and sampling, coupled to solid phase extraction and mass spectrometry (SPE-MS), for monitoring non-esterified fatty acid (NEFA) secretion profiles from adipocytes [49]. (B) Average NEFA secretion profiles during basal and isoproterenol/forskolin stimulation of adipocytes using the chip in (A) for stimulation and sampling. (C) On-chip culture systems for primary adipose tissue [42]. Primary mouse adipocytes were cultured in a 3D collagen matrix (top left) on an 8-channel microfluidic sampling device. Alternatively, explants were trapped using customized traps. 3D CAD rendering (top right) is shown with 3D-printed explant traps (middle right). (D) Temporal program of combined insulin, glucose, and fatty acid inputs to adipose explants using a microfluidic multiplexer (μMUX) device [39]. (E) Real-time fatty acid uptake responses from treatments in (D) showed insulin-dependent exchange rates. (F) Representative fluorescent images of on-chip explants used to generate data in (E). (G) Compiled data from (E) showed insulin-dependent fatty acid exchange dynamics. (H) Assignment map of the programmable, automated μMUX device, showing the 10 required input channels and one output waste channel used for (D)–(G). Reproduced from references 39, 42, and 49 with permission from the Royal Society of Chemistry and from Springer Publishing Company

Article Snippet: As shown in the table, within the past several years, researchers have devised a number of trapping methods that can be chosen by those interested in using microfluidics to study adipose tissue dynamics. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 1 caption a7 Recent examples of microfluidic systems for studying dynamic function of adipocytes and adipose tissue. ( A ) Schematic of microfluidic device for 3T3-L1 adipocyte stimulation and sampling, coupled to solid phase extraction and mass spectrometry (SPE-MS), for monitoring non-esterified fatty acid (NEFA) secretion profiles from adipocytes [ 49 ]. ( B ) Average NEFA secretion profiles during basal and isoproterenol/forskolin stimulation of adipocytes using the chip in (A) for stimulation and sampling. ( C ) On-chip culture systems for primary adipose tissue [ 42 ].

Techniques: Sampling, Extraction, Mass Spectrometry, Cell Culture

Journal: Analytical and bioanalytical chemistry

Article Title: Microfluidic systems for studying dynamic function of adipocytes and adipose tissue

doi: 10.1007/s00216-017-0741-8

Figure Lengend Snippet: Recent approaches for integrating adipose tissue or pre-differentiated cells onto microfluidic devices for dynamic functional studies

Article Snippet: As shown in the table, within the past several years, researchers have devised a number of trapping methods that can be chosen by those interested in using microfluidics to study adipose tissue dynamics. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 1 caption a7 Recent examples of microfluidic systems for studying dynamic function of adipocytes and adipose tissue. ( A ) Schematic of microfluidic device for 3T3-L1 adipocyte stimulation and sampling, coupled to solid phase extraction and mass spectrometry (SPE-MS), for monitoring non-esterified fatty acid (NEFA) secretion profiles from adipocytes [ 49 ]. ( B ) Average NEFA secretion profiles during basal and isoproterenol/forskolin stimulation of adipocytes using the chip in (A) for stimulation and sampling. ( C ) On-chip culture systems for primary adipose tissue [ 42 ].

Techniques: Functional Assay, Fluorescence, Enzymatic Assay, Sampling, Enzyme-linked Immunosorbent Assay, Comparison, Extraction, Mass Spectrometry, Imaging

Journal: Biomicrofluidics

Article Title: Biomimetic tumor microenvironment on a microfluidic platform

doi: 10.1063/1.4774070

Figure Lengend Snippet: Fibroblasts involved in the tumor microenvironment. (a) Fibroblasts can be activated by tumor cells in the fluidic channels of the cell culture chip with pneumatic micro-valves. The activated fibroblasts appeared as the stretched body and high expression of α-SMA under the treatment of the cancer cell medium.55 Reprinted with permission from T.-H. Hsu et al., Lab Chip 11, 1808 (2011). Copyright 2011 The Royal Society of Chemistry. (b) The invasive transition of breast cancer cells can be seen after co-cultured with fibroblasts on the Y-shaped microfluidic chip.56 Reprinted with permission from K. E. Sung et al., Integr. Biol. 3, 439 (2011). Copyright 2011 The Royal Society of Chemistry. (c) Carcinoma-associated fibroblasts promoted tumor invasion in the spheroid mode on a microfluidic 3D co-culture device.62 Reprinted with permission from T. Liu et al., Lab Chip 10, 1671 (2010). Copyright 2010 The Royal Society of Chemistry.

Article Snippet: The obvious advantages obtained by this device are that it can reproduce anastomosis process with functional vessel, by accurately lining the endothelial cells adjacent the collagen gel and precise control of the physiological flow within microstructure, thus providing a novel approach to study the mechanisms of angiogenesis in cancer development. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 4 caption a7 The endothelial sprouting and new blood vessel formation in biomimetic tumor microenvironment. (a) Schematic representation of a microfluidic device showing two parallel main channels, which provide media and nutrients to the gel channels to support cell co-culture between MSCs and endothelial cells.

Techniques: Cell Culture, Expressing, Co-Culture Assay

Journal: Biomicrofluidics

Article Title: Biomimetic tumor microenvironment on a microfluidic platform

doi: 10.1063/1.4774070

Figure Lengend Snippet: The endothelial sprouting and new blood vessel formation in biomimetic tumor microenvironment. (a) Schematic representation of a microfluidic device showing two parallel main channels, which provide media and nutrients to the gel channels to support cell co-culture between MSCs and endothelial cells.66 Confocal images shown in an orthogonal display confirmed the presence of hollow lumens in the forming capillary-like structure. Reprinted with permission from B. Carrion et al., Biotechnol. Bioeng. 107, 1020 (2010). Copyright 2010 John Wiley and Sons. (b) Microfluidic device with localized 3D ECM used for endothelial sprounting67 and new functional microvessel formation by anastomosis in vitro. Particle (white arrow) advection through the lumen can be seen from pictures captured from the video.68 Reprinted with permission from J. W. Song and L. L. Munn, Proc. Natl Acad. Sci. U.S.A. 108, 15342 (2011). Copyright 2011 National Academy of Sciences; J. W. Song et al., Integr. Biol. 4, 857 (2012). Copyright 2012 The Royal Society of Chemistry.

Article Snippet: The obvious advantages obtained by this device are that it can reproduce anastomosis process with functional vessel, by accurately lining the endothelial cells adjacent the collagen gel and precise control of the physiological flow within microstructure, thus providing a novel approach to study the mechanisms of angiogenesis in cancer development. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 4 caption a7 The endothelial sprouting and new blood vessel formation in biomimetic tumor microenvironment. (a) Schematic representation of a microfluidic device showing two parallel main channels, which provide media and nutrients to the gel channels to support cell co-culture between MSCs and endothelial cells.

Techniques: Co-Culture Assay, Functional Assay, In Vitro

Journal: Biomicrofluidics

Article Title: Biomimetic tumor microenvironment on a microfluidic platform

doi: 10.1063/1.4774070

Figure Lengend Snippet: The process of intravasation and extravasation recapitulated on the biomimetic microfluidic devices. (a) The adhesion of cancer cells on the endothelium layer was region-specifically investigated under physiological flow conditions on the microfluidic vasculature.70 Reprinted with permission from J. W. Song et al., PLoS ONE 4, e5756 (2009). Copyright 2009 Public Library of Science. (b) Microfluidic tumor-vascular interface model for tumor cells intravasation study. The confluent endothelial monolayer can be formed on the 3D ECM. In the process of intravasaton, breast carcinoma cell (white arrow) migrated across the HUVEC mono layer (magenta) in the presence of macrophage.71 Reprinted with permission from I. K. Zervantonakis et al., Proc. Natl Acad. Sci. U.S.A. 109, 13515 (2012). Copyright 2012 National Academy of Sciences. (c) Mimicking the extravasation process of tumor aggregates from the endothelial layer based on the bioengineering blood vessel model.72 Reprinted with permission from Q. Zhang et al., Lab Chip 12, 2837 (2012). Copyright 2012 The Royal Society of Chemistry.

Article Snippet: The obvious advantages obtained by this device are that it can reproduce anastomosis process with functional vessel, by accurately lining the endothelial cells adjacent the collagen gel and precise control of the physiological flow within microstructure, thus providing a novel approach to study the mechanisms of angiogenesis in cancer development. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 4 caption a7 The endothelial sprouting and new blood vessel formation in biomimetic tumor microenvironment. (a) Schematic representation of a microfluidic device showing two parallel main channels, which provide media and nutrients to the gel channels to support cell co-culture between MSCs and endothelial cells.

Techniques: