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Article: Disposable microfluidic devices: fabrication, function, and application.

Fiorini, Gina S / Chiu, Daniel T

2005 Volume 38, Issue 3, Page(s) 429–446

Abstract: This review article describes recent developments in microfluidics, with special emphasis on disposable plastic devices. Included is an overview of the common methods used in the fabrication of polymer microfluidic systems, including replica and ... ...

Abstract	This review article describes recent developments in microfluidics, with special emphasis on disposable plastic devices. Included is an overview of the common methods used in the fabrication of polymer microfluidic systems, including replica and injection molding, embossing, and laser ablation. Also described are the different methods by which on-chip operations--such as the pumping and valving of fluid flow, the mixing of different reagents, and the separation and detection of different chemical species--have been implemented in a microfluidic format. Finally, a few select biotechnological applications of microfluidics are presented to illustrate both the utility of this technology and its potential for development in the future.
MeSH term(s)	Biosensing Techniques/instrumentation ; Biosensing Techniques/methods ; Biosensing Techniques/trends ; Chemistry Techniques, Analytical/instrumentation ; Chemistry Techniques, Analytical/methods ; Chemistry Techniques, Analytical/trends ; Disposable Equipment ; Equipment Design ; Equipment Failure Analysis ; Microarray Analysis/instrumentation ; Microarray Analysis/methods ; Microarray Analysis/trends ; Microfluidic Analytical Techniques/instrumentation ; Microfluidic Analytical Techniques/methods ; Microfluidic Analytical Techniques/trends ; Technology Assessment, Biomedical
Language	English
Publishing date	2005-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	48453-2
ISSN	1940-9818 ; 0736-6205
ISSN (online)	1940-9818
ISSN	0736-6205
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Article ; Online: Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19.

Carmona-Rivera, Carmelo / Zhang, Yu / Dobbs, Kerry / Markowitz, Tovah E / Dalgard, Clifton L / Oler, Andrew J / Claybaugh, Dillon R / Draper, Deborah / Truong, Meng / Delmonte, Ottavia M / Licciardi, Francesco / Ramenghi, Ugo / Crescenzio, Nicoletta / Imberti, Luisa / Sottini, Alessandra / Quaresima, Virginia / Fiorini, Chiara / Discepolo, Valentina / Lo Vecchio, Andrea /

Guarino, Alfredo / Pierri, Luca / Catzola, Andrea / Biondi, Andrea / Bonfanti, Paolo / Poli Harlowe, Maria C / Espinosa, Yasmin / Astudillo, Camila / Rey-Jurado, Emma / Vial, Cecilia / de la Cruz, Javiera / Gonzalez, Ricardo / Pinera, Cecilia / Mays, Jacqueline W / Ng, Ashley / Platt, Andrew / Drolet, Beth / Moon, John / Cowen, Edward W / Kenney, Heather / Weber, Sarah E / Castagnoli, Riccardo / Magliocco, Mary / Stack, Michael A / Montealegre, Gina / Barron, Karyl / Fink, Danielle L / Kuhns, Douglas B / Hewitt, Stephen M / Arkin, Lisa M / Chertow, Daniel S / Su, Helen C / Notarangelo, Luigi D / Kaplan, Mariana J

JCI insight

2022 Volume 7, Issue 16

Abstract: Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in ...

Abstract	Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as "COVID toes," remains unclear. Studying multinational cohorts, we found that, in CLLs, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs after disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased NET levels when compared with other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.
MeSH term(s)	Actins/metabolism ; Adult ; COVID-19/complications ; Child ; Deoxyribonuclease I ; Extracellular Traps ; Humans ; Neutrophils ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome
Chemical Substances	Actins ; Deoxyribonuclease I (EC 3.1.21.1)
Language	English
Publishing date	2022-08-22
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.160332
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Article: Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19.

Guarino, Alfredo / Pierri, Luca / Catzola, Andrea / Biondi, Andrea / Bonfanti, Paolo / Poli Harlowe, Maria Cecilia / Espinosa, Yasmin / Astudillo, Camila / Rey-Jurado, Emma / Vial, Cecilia / de la Cruz, Javiera / Gonzalez, Ricardo / Pinera, Cecilia / Mays, Jacqueline W / Ng, Ashley / Platt, Andrew / Drolet, Beth / Moon, John / Cowen, Edward W / Kenney, Heather / Weber, Sarah E / Castagnoli, Riccardo / Magliocco, Mary / Stack, Michael A / Montealegre, Gina / Barron, Karyl / Hewitt, Stephen M / Arkin, Lisa M / Chertow, Daniel S / Su, Helen C / Notarangelo, Luigi D / Kaplan, Mariana J

medRxiv : the preprint server for health sciences

2022

Abstract: Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease including MIS-C and chilblain-like lesions (CLL) ...

Abstract	Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease including MIS-C and chilblain-like lesions (CLL), otherwise known as "COVID toes", remains unclear. Studying multinational cohorts, we found that, in CLL, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs post-disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased levels of NETs when compared to other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients. Summary: NET formation and degradation are dysregulated in pediatric and symptomatic adult patients with various complications of COVID-19, in association with disease severity. NET degradation impairments are multifactorial and associated with natural inhibitors of DNase 1, G-actin and anti-DNase1L3 and anti-NET antibodies. Infection with the Omicron variant is associated with decreased levels of NETs when compared to other SARS-CoV-2 strains.
Language	English
Publishing date	2022-03-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.02.24.22271475
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Article ; Online: Disposable microfluidic devices

Gina S. Fiorini / Daniel T. Chiu

BioTechniques, Vol 38, Iss 3, Pp 429-

fabrication, function, and application

2005 Volume 446

Abstract	This review article describes recent developments in microfluidics, with special emphasis on disposable plastic devices. Included is an overview of the common methods used in the fabrication of polymer microfluidic systems, including replica and injection molding, embossing, and laser ablation. Also described are the different methods by which on-chip operations—such as the pumping and valving of fluid flow, the mixing of different reagents, and the separation and detection of different chemical species—have been implemented in a microfluidic format. Finally, a few select biotechnological applications of microfluidics are presented to illustrate both the utility of this technology and its potential for development in the future.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2005-03-01T00:00:00Z
Publisher	Future Science Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: In-channel atom-transfer radical polymerization of thermoset polyester microfluidic devices for bioanalytical applications.

Pan, Tao / Fiorini, Gina S / Chiu, Daniel T / Woolley, Adam T

Electrophoresis

2007 Volume 28, Issue 16, Page(s) 2904–2911

Abstract: A new technique for polymer microchannel surface modification, called in-channel atom-transfer radical polymerization, has been developed and applied in the surface derivatization of thermoset polyester (TPE) microdevices with poly(ethylene glycol) (PEG). ...

Abstract	A new technique for polymer microchannel surface modification, called in-channel atom-transfer radical polymerization, has been developed and applied in the surface derivatization of thermoset polyester (TPE) microdevices with poly(ethylene glycol) (PEG). X-ray photoelectron spectroscopy, electroosmotic flow (EOF), and contact angle measurements indicate that PEG has been grafted on the TPE surface. Moreover, PEG-modified microchannels have much lower and more pH-stable EOF, more hydrophilic surfaces and reduced nonspecific protein adsorption. Capillary electrophoresis separation of amino acid and peptide mixtures in these PEG-modified TPE microchips had good reproducibility. Phosducin-like protein and phosphorylated phosducin-like protein were also separated to measure the phosphorylation efficiency. Our results indicate that PEG-grafted TPE microchips have broad potential application in biomolecular analysis.
MeSH term(s)	Adsorption ; Amino Acids/analysis ; Electrophoresis, Microchip/instrumentation ; Electrophoresis, Microchip/methods ; Electrophoresis, Microchip/statistics & numerical data ; Fluorescein-5-isothiocyanate ; Fluorescent Dyes ; Microfluidic Analytical Techniques/instrumentation ; Microfluidic Analytical Techniques/methods ; Microfluidic Analytical Techniques/statistics & numerical data ; Peptides/analysis ; Polyesters ; Polyethylene Glycols ; Proteins/analysis
Chemical Substances	Amino Acids ; Fluorescent Dyes ; Peptides ; Polyesters ; Proteins ; Polyethylene Glycols (30IQX730WE) ; Fluorescein-5-isothiocyanate (I223NX31W9)
Language	English
Publishing date	2007-08
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	619001-7
ISSN	1522-2683 ; 0173-0835
ISSN (online)	1522-2683
ISSN	0173-0835
DOI	10.1002/elps.200600817
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Article: Rapid prototyping of thermoset polyester microfluidic devices.

Fiorini, Gina S / Lorenz, Robert M / Kuo, Jason S / Chiu, Daniel T

Analytical chemistry

2004 Volume 76, Issue 16, Page(s) 4697–4704

Abstract: ... electroosmotic mobility of 1.3 x 10(-4) cm(2) V(-1) s(-1) for a 50-microm square channel (20 mM borate at pH 9 ...

Abstract	This paper presents a simple procedure for the fabrication of thermoset polyester (TPE) microfluidic systems and discusses the properties of the final devices. TPE chips are fabricated in less than 3 h by casting TPE resin directly on a lithographically patterned (SU-8) silicon master. Thorough curing of the devices is obtained through the combined use of ultraviolet light and heat, as both an ultraviolet and a thermal initiator are employed in the resin mixture. Features on the order of micrometers and greater are routinely reproduced using the presented procedure, including complex designs and multilayer features. The surface of TPE was characterized using contact angle measurements and X-ray photoelectron spectroscopy (XPS). Following oxygen plasma treatment, the hydrophilicity of the surface of TPE increases (determined by contact angle measurements) and the proportion of oxygen-containing functional groups also increases (determined by XPS), which indicates a correlated increase in the charge density on the surface. Native TPE microchannels support electroosmotic flow (EOF) toward the cathode, with an average electroosmotic mobility of 1.3 x 10(-4) cm(2) V(-1) s(-1) for a 50-microm square channel (20 mM borate at pH 9); following plasma treatment (5 min at 30 W and 0.3 mbar), EOF is enhanced by a factor of 2. This enhancement of the EOF from plasma treatment is stable for days, with no significant decrease noted during the 5-day period that we monitored. Using plasma-treated TPE microchannels, we demonstrate the separation of a mixture of fluorescein-tagged amino acids (glycine, glutamic acid, aspartic acid). TPE devices are up to 90% transparent (for approximately 2-mm-thick sample) to visible light (400-800 nm). The compatibility of TPE with a wide range of solvents was tested over a 24-h period, and the material performed well with acids, bases, alcohols, cyclohexane, n-heptane, and toluene but not with chlorinated solvents (dichloromethane, chloroform).
MeSH term(s)	Microfluidic Analytical Techniques/methods ; Microscopy, Electron, Scanning/methods ; Osmosis ; Polyesters ; Silicon ; Surface Properties
Chemical Substances	Polyesters ; Silicon (Z4152N8IUI)
Language	English
Publishing date	2004-08-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/ac0498922
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Article ; Online: Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19

Carmelo Carmona-Rivera / Yu Zhang / Kerry Dobbs / Tovah E. Markowitz / Clifton L. Dalgard / Andrew J. Oler / Dillon R. Claybaugh / Deborah Draper / Meng Truong / Ottavia M. Delmonte / Francesco Licciardi / Ugo Ramenghi / Nicoletta Crescenzio / Luisa Imberti / Alessandra Sottini / Virginia Quaresima / Chiara Fiorini / Valentina Discepolo / Andrea Lo Vecchio /

Alfredo Guarino / Luca Pierri / Andrea Catzola / Andrea Biondi / Paolo Bonfanti / Maria C. Poli Harlowe / Yasmin Espinosa / Camila Astudillo / Emma Rey-Jurado / Cecilia Vial / Javiera de la Cruz / Ricardo Gonzalez / Cecilia Pinera / Jacqueline W. Mays / Ashley Ng / Andrew Platt / NIH COVID Autopsy Consortium / COVID STORM Clinicians / Beth Drolet / John Moon / Edward W. Cowen / Heather Kenney / Sarah E. Weber / Riccardo Castagnoli / Mary Magliocco / Michael A. Stack / Gina Montealegre / Karyl Barron / Danielle L. Fink / Douglas B. Kuhns / Stephen M. Hewitt / Lisa M. Arkin / Daniel S. Chertow / Helen C. Su / Luigi D. Notarangelo / Mariana J. Kaplan

JCI Insight, Vol 7, Iss

2022 Volume 16

Abstract	Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as “COVID toes,” remains unclear. Studying multinational cohorts, we found that, in CLLs, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs after disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19–affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased NET levels when compared with other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.
Keywords	Infectious disease ; Inflammation ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Simultaneous generation of multiple aqueous droplets in a microfluidic device.

Lorenz, Robert M / Fiorini, Gina S / Jeffries, Gavin D M / Lim, David S W / He, Mingyan / Chiu, Daniel T

Analytica chimica acta

2008 Volume 630, Issue 2, Page(s) 124–130

Abstract: This paper describes a microfluidic platform for the on-demand generation of multiple aqueous droplets, with varying chemical contents or chemical concentrations, for use in droplet based experiments. This generation technique was developed as a ... ...

Abstract	This paper describes a microfluidic platform for the on-demand generation of multiple aqueous droplets, with varying chemical contents or chemical concentrations, for use in droplet based experiments. This generation technique was developed as a complement to existing techniques of continuous-flow (streaming) and discrete-droplet generation by enabling the formation of multiple discrete droplets simultaneously. Here sets of droplets with varying chemical contents can be generated without running the risk of cross-contamination due to the isolated nature of each supply inlet. The use of pressure pulses to generate droplets in parallel is described, and the effect of droplet size is examined in the context of flow rates and surfactant concentrations. To illustrate this technique, an array of different dye-containing droplets was generated, as well as a set of droplets that displayed a concentration gradient of a fluorescent dye.
MeSH term(s)	Microfluidic Analytical Techniques/instrumentation ; Microfluidic Analytical Techniques/methods ; Oils/chemistry ; Surface-Active Agents/chemistry ; Water/chemistry
Chemical Substances	Oils ; Surface-Active Agents ; Water (059QF0KO0R)
Language	English
Publishing date	2008-10-14
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1483436-4
ISSN	1873-4324 ; 0003-2670
ISSN (online)	1873-4324
ISSN	0003-2670
DOI	10.1016/j.aca.2008.10.009
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Article: In-channel atom-transfer radical polymerization of thermoset polyester microfluidic devices for bioanalytical applications

Pan, Tao / Fiorini, Gina S / Chiu, Daniel T / Woolley, Adam T

Electrophoresis. 2007 Aug., v. 28, no. 16

2007

Abstract	A new technique for polymer microchannel surface modification, called in-channel atom-transfer radical polymerization, has been developed and applied in the surface derivatization of thermoset polyester (TPE) microdevices with poly(ethylene glycol) (PEG). X-ray photoelectron spectroscopy, electroosmotic flow (EOF), and contact angle measurements indicate that PEG has been grafted on the TPE surface. Moreover, PEG-modified microchannels have much lower and more pH-stable EOF, more hydrophilic surfaces and reduced nonspecific protein adsorption. Capillary electrophoresis separation of amino acid and peptide mixtures in these PEG-modified TPE microchips had good reproducibility. Phosducin-like protein and phosphorylated phosducin-like protein were also separated to measure the phosphorylation efficiency. Our results indicate that PEG-grafted TPE microchips have broad potential application in biomolecular analysis.
Keywords	X-ray photoelectron spectroscopy ; adsorption ; amino acids ; capillary electrophoresis ; contact angle ; derivatization ; ethylene glycol ; hydrophilicity ; phosphorylation ; polyesters ; polymerization
Language	English
Dates of publication	2007-08
Size	p. 2904-2911.
Publishing place	Wiley-VCH Verlag
Document type	Article
ZDB-ID	619001-7
ISSN	1522-2683 ; 0173-0835
ISSN (online)	1522-2683
ISSN	0173-0835
DOI	10.1002/elps.200600817
Database	NAL-Catalogue (AGRICOLA)

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Article: High-power blue/UV light-emitting diodes as excitation sources for sensitive detection.

Kuo, Jason S / Kuyper, Christopher L / Allen, Peter B / Fiorini, Gina S / Chiu, Daniel T

Electrophoresis

2004 Volume 25, Issue 21-22, Page(s) 3796–3804

Abstract: With advances in III-V nitride manufacturing processes, high-power light-emitting diode (LED) chips in the blue and UV wavelengths are now commercially available at reasonable cost and can be used as excitation sources in optical sensing. We describe the ...

Abstract	With advances in III-V nitride manufacturing processes, high-power light-emitting diode (LED) chips in the blue and UV wavelengths are now commercially available at reasonable cost and can be used as excitation sources in optical sensing. We describe the use of these high-power blue and UV LEDs for sensitive fluorescence detection, including chip-based flow cytometry, capillary electrophoresis (CE), and single-molecule imaging. By using a blue LED with a focusable power of approximately 40 mW as the excitation source for fluorescent beads, we demonstrate a simple chip-based bead sorter capable of enriching the concentration of green fluorescent beads from 63% to 95%. In CE experiments, we show that a mixture of analyte solution containing 30 nM 6-carboxyrhodamine 6G and 10 nM fluorescein can be separated and detected with excellent signal-to-noise ratio (approximately 17 for 10 nM fluorescein) using the collimated emission from a blue LED; the estimated mass detection limit was approximately 200 zmol for fluorescein. We also demonstrated ultrasensitive fluorescence imaging of single rhodamine 123 molecules and individual lambda-DNA molecules. At a small fraction of the cost of an Ar+ laser, high-power blue and UV LEDs are effective alternatives for lasers and arc lamps in fluorescence applications that demand portability, low cost, and convenience.
MeSH term(s)	Cells ; Diagnostic Imaging/instrumentation ; Electrophoresis, Capillary ; Flow Cytometry ; Fluorescence ; Lab-On-A-Chip Devices ; Light ; Optics and Photonics/instrumentation ; Ultraviolet Rays
Language	English
Publishing date	2004-11
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	619001-7
ISSN	1522-2683 ; 0173-0835
ISSN (online)	1522-2683
ISSN	0173-0835
DOI	10.1002/elps.200406118
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