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Article ; Online: High-Throughput Processing to Preserve Viable Cells: A Precision Medicine Initiative Cohort Program Workshop.

Rasooly, Rebekah S / Gossett, Daniel R / Henderson, Marianne K / Hubel, Allison / Thibodeau, Stephen N

2017 Volume 15, Issue 4, Page(s) 341–343

Abstract: Conventionally, biobanks supporting clinical research studies have preserved serum, plasma, urine, saliva, a variety of tissue types, and stool. With the emergence of increasingly sophisticated technologies for analyzing single cells, there is growing ... ...

Abstract	Conventionally, biobanks supporting clinical research studies have preserved serum, plasma, urine, saliva, a variety of tissue types, and stool. With the emergence of increasingly sophisticated technologies for analyzing single cells, there is growing interest in preserving viable blood cells for future functional studies. The new All of Us Research Program (formerly the Precision Medicine Initiative Cohort Program) biobank plans to house samples from a million or more individuals as part of a cohort with rich phenotypic data and longitudinal follow-up ( www.nih.gov/research-training/allofus-research-program ). Storage of viable cells for future single-cell analysis offers the promise of new biology, discovery of novel biomarkers, and advances toward the goal of precision medicine. A workshop was held in the summer of 2016 to evaluate the case for preservation of viable mononuclear blood cells and its feasibility within the collection plan for the biobank.
MeSH term(s)	Biomedical Research/education ; Biomedical Research/trends ; Blood Specimen Collection/methods ; Blood Specimen Collection/standards ; Cell Survival ; Education ; Humans ; Leukocytes, Mononuclear/cytology ; Precision Medicine/methods
Language	English
Publishing date	2017-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2593993-2
ISSN	1947-5543 ; 1947-5535
ISSN (online)	1947-5543
ISSN	1947-5535
DOI	10.1089/bio.2017.0016
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Article ; Online: Three dimensional, sheathless, and high-throughput microparticle inertial focusing through geometry-induced secondary flows.

Chung, Aram J / Gossett, Daniel R / Di Carlo, Dino

Small (Weinheim an der Bergstrasse, Germany)

2013 Volume 9, Issue 5, Page(s) 685–690

Abstract: A novel inertial focusing platform creates a single-stream microparticle train in a single-focal plane without sheath fluids and external forces, all in a high-throughput manner. The proposed design consists of a low-aspect-ratio straight channel ... ...

Abstract	A novel inertial focusing platform creates a single-stream microparticle train in a single-focal plane without sheath fluids and external forces, all in a high-throughput manner. The proposed design consists of a low-aspect-ratio straight channel interspersed with a series of constrictions in height arranged orthogonally, making use of inertial focusing and geometry-induced secondary flows. Focusing efficiency as high as 99.77% is demonstrated with throughput as high as 36 000 particles s(-1) for a variety of different sized particles and cells.
Language	English
Publishing date	2013-03-11
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1613-6829
ISSN (online)	1613-6829
DOI	10.1002/smll.201202413
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Article: RNA methyltransferase SPOUT1/CENP-32 links mitotic spindle organization with the neurodevelopmental disorder SpADMiSS.

Dharmadhikari, Avinash V / Abad, Maria Alba / Khan, Sheraz / Maroofian, Reza / Sands, Tristan T / Ullah, Farid / Samejima, Itaru / Wear, Martin A / Moore, Kiara E / Kondakova, Elena / Mitina, Natalia / Schaub, Theres / Lee, Grace K / Umandap, Christine H / Berger, Sara M / Iglesias, Alejandro D / Popp, Bernt / Jamra, Rami Abou / Gabriel, Heinz /

Rentas, Stefan / Rippert, Alyssa L / Izumi, Kosuke / Conlin, Laura K / Koboldt, Daniel C / Mosher, Theresa Mihalic / Hickey, Scott E / Albert, Dara V F / Norwood, Haley / Lewanda, Amy Feldman / Dai, Hongzheng / Liu, Pengfei / Mitani, Tadahiro / Marafi, Dana / Pehlivan, Davut / Posey, Jennifer E / Lippa, Natalie / Vena, Natalie / Heinzen, Erin L / Goldstein, David B / Mignot, Cyril / de Sainte Agathe, Jean-Madeleine / Al-Sannaa, Nouriya Abbas / Zamani, Mina / Sadeghian, Saeid / Azizimalamiri, Reza / Seifia, Tahere / Zaki, Maha S / Abdel-Salam, Ghada M H / Abdel-Hamid, Mohamed / Alabdi, Lama / Alkuraya, Fowzan Sami / Dawoud, Heba / Lofty, Aya / Bauer, Peter / Zifarelli, Giovanni / Afzal, Erum / Zafar, Faisal / Efthymiou, Stephanie / Gossett, Daniel / Towne, Meghan C / Yeneabat, Raey / Wontakal, Sandeep N / Aggarwal, Vimla S / Rosenfeld, Jill A / Tarabykin, Victor / Ohta, Shinya / Lupski, James R / Houlden, Henry / Earnshaw, William C / Davis, Erica E / Jeyaprakash, A Arockia / Liao, Jun

medRxiv : the preprint server for health sciences

2024

Abstract: SPOUT1/CENP- ... ...

Abstract	SPOUT1/CENP-32
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.09.23300329
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Article ; Online: Introduction: why analyze single cells?

Di Carlo, Dino / Tse, Henry Tat Kwong / Gossett, Daniel R

Methods in molecular biology (Clifton, N.J.)

2012 Volume 853, Page(s) 1–10

Abstract: Powerful methods in molecular biology are abundant; however, in many fields including hematology, stem cell biology, tissue engineering, and cancer biology, data from tools and assays that analyze the average signals from many cells may not yield the ... ...

Abstract	Powerful methods in molecular biology are abundant; however, in many fields including hematology, stem cell biology, tissue engineering, and cancer biology, data from tools and assays that analyze the average signals from many cells may not yield the desired result because the cells of interest may be in the minority-their behavior masked by the majority-or because the dynamics of the populations of interest are offset in time. Accurate characterization of samples with high cellular heterogeneity may only be achieved by analyzing single cells. In this chapter, we discuss the rationale for performing analyses on individual cells in more depth, cover the fields of study in which single-cell behavior is yielding new insights into biological and clinical questions, and speculate on how single-cell analysis will be critical in the future.
MeSH term(s)	Animals ; Gene Expression Profiling/instrumentation ; Gene Expression Profiling/methods ; Humans ; Microfluidic Analytical Techniques/instrumentation ; Microfluidic Analytical Techniques/methods ; Microtechnology ; Single-Cell Analysis/instrumentation ; Single-Cell Analysis/methods
Language	English
Publishing date	2012
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-61779-567-1_1
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Article ; Online: Mediating millisecond reaction time around particles and cells.

Dudani, Jaideep S / Go, Derek E / Gossett, Daniel R / Tan, Andrew P / Di Carlo, Dino

Analytical chemistry

2014 Volume 86, Issue 3, Page(s) 1502–1510

Abstract: Precise spatiotemporal control of how particles and cells interact with reagents is critical for numerous laboratory and industrial processes. Novel tools for exerting this control at shorter time scales will enable development of new chemical processes ... ...

Abstract	Precise spatiotemporal control of how particles and cells interact with reagents is critical for numerous laboratory and industrial processes. Novel tools for exerting this control at shorter time scales will enable development of new chemical processes and biomedical assays. Previously, we have developed a generalized approach to manipulate cells and particles across fluid streams termed rapid inertial solution exchange (RInSE), which utilizes inertial lift forces at finite Reynolds number and high Peclet number to transfer particles from an initial solution to another within a millisecond. Here, we apply these principles toward developing a continuous flow microfluidic platform that enables transient chemical treatments of cells and particles (on the order of 1 ms). We also demonstrate how the reactant stream can be employed as a diffusion barrier, preventing adverse reactions between coflowing solutions. In order to demonstrate the utility of the method, we applied it to various operations in molecular biology and automated cell staining including cell permeabilization, fluorescent staining, and molecular delivery to viable cells. We expect this method will enable previously unexplored studies of the dynamics of molecular events, improve uniformity of reactions carried on the surface of beads, and increase uniformity in cell-based assays through automation.
MeSH term(s)	Cell Survival ; Equipment Design ; HeLa Cells ; Humans ; MCF-7 Cells ; Microfluidic Analytical Techniques/instrumentation ; Microfluidic Analytical Techniques/methods ; Permeability ; Staining and Labeling ; Time Factors
Language	English
Publishing date	2014-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/ac402920m
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Article ; Online: Particle focusing mechanisms in curving confined flows.

Gossett, Daniel R / Di Carlo, Dino

Analytical chemistry

2009 Volume 81, Issue 20, Page(s) 8459–8465

Abstract: Particles in finite-inertia confined channel flows are known to segregate and focus to equilibrium positions whose number corresponds with the fold of symmetry of the channel's cross section. The addition of curvature into channels presumably modifies ... ...

Abstract	Particles in finite-inertia confined channel flows are known to segregate and focus to equilibrium positions whose number corresponds with the fold of symmetry of the channel's cross section. The addition of curvature into channels presumably modifies these equilibrium inertial focusing positions, because of the secondary flow induced in curved channels. Here, we identify the critical interaction of the secondary flow field with inertial lift forces to create complex sets of particle focusing positions that vary with the channel Reynolds number (Re(C)) and the inertial force ratio, which is a new dimensionless parameter that is based on the ratio of inertial lift to drag forces from the secondary flow. We use these results to identify microfluidic channel geometries to focus particles at rates an order of magnitude higher than previously shown (channel Reynolds number, Re(C) = 270) and develop design criteria for the focusing of potentially arbitrary-sized particles. In addition, our results indicate that channel curvature can lead to microfluidic designs with reduced fluidic resistance, useful for lower power inertial focusing or separation. These results will enable design of practical particle/cell separation, filtration, and focusing systems for critical applications in biomedicine and environmental cleanup.
MeSH term(s)	Microfluidic Analytical Techniques/instrumentation ; Microfluidic Analytical Techniques/methods ; Microfluidics ; Motion
Language	English
Publishing date	2009-10-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/ac901306y
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Article ; Online: Statistical methods for building better biomarkers of chronic kidney disease.

Pencina, Michael J / Parikh, Chirag R / Kimmel, Paul L / Cook, Nancy R / Coresh, Josef / Feldman, Harold I / Foulkes, Andrea / Gimotty, Phyllis A / Hsu, Chi-Yuan / Lemley, Kevin / Song, Peter / Wilkins, Kenneth / Gossett, Daniel R / Xie, Yining / Star, Robert A

Statistics in medicine

2019 Volume 38, Issue 11, Page(s) 1903–1917

Abstract: The last two decades have witnessed an explosion in research focused on the development and assessment of novel biomarkers for improved prognosis of diseases. As a result, best practice standards guiding biomarker research have undergone extensive ... ...

Abstract	The last two decades have witnessed an explosion in research focused on the development and assessment of novel biomarkers for improved prognosis of diseases. As a result, best practice standards guiding biomarker research have undergone extensive development. Currently, there is great interest in the promise of biomarkers to enhance research efforts and clinical practice in the setting of chronic kidney disease, acute kidney injury, and glomerular disease. However, some have questioned whether biomarkers currently add value to the clinical practice of nephrology. The current state of the art pertaining to statistical analyses regarding the use of such measures is critical. In December 2014, the National Institute of Diabetes and Digestive and Kidney Diseases convened a meeting, "Toward Building Better Biomarker Statistical Methodology," with the goals of summarizing the current best practice recommendations and articulating new directions for methodological research. This report summarizes its conclusions and describes areas that need attention. Suggestions are made regarding metrics that should be commonly reported. We outline the methodological issues related to traditional metrics and considerations in prognostic modeling, including discrimination and case mix, calibration, validation, and cost-benefit analysis. We highlight the approach to improved risk communication and the value of graphical displays. Finally, we address some "new frontiers" in prognostic biomarker research, including the competing risk framework, the use of longitudinal biomarkers, and analyses in distributed research networks.
MeSH term(s)	Adult ; Aged ; Biomarkers ; Cost-Benefit Analysis ; Humans ; Middle Aged ; Models, Statistical ; Prognosis ; Renal Insufficiency, Chronic/physiopathology ; Risk Assessment/statistics & numerical data
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-01-21
Publishing country	England
Document type	Journal Article
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.8091
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Article: Rapid inertial solution exchange for enrichment and flow cytometric detection of microvesicles.

Dudani, Jaideep S / Gossett, Daniel R / Tse, Henry T K / Lamm, Robert J / Kulkarni, Rajan P / Carlo, Dino Di

Biomicrofluidics

2015 Volume 9, Issue 1, Page(s) 14112

Abstract: Exosomes, nanosized membrane-bound vesicles released by cells, play roles in cell signaling, immunology, virology, and oncology. Their study, however, has been hampered by difficulty in isolation and quantification due to their size and the complexity of ...

Abstract	Exosomes, nanosized membrane-bound vesicles released by cells, play roles in cell signaling, immunology, virology, and oncology. Their study, however, has been hampered by difficulty in isolation and quantification due to their size and the complexity of biological samples. Conventional approaches to improved isolation require specialized equipment and extensive sample preparation time. Therefore, isolation and detection methods of exosomes will benefit biological and clinical studies. Here, we report a microfluidic platform for inline exosome isolation and fluorescent detection using inertial manipulation of antibody-coated exosome capture beads from biological fluids.
Language	English
Publishing date	2015-02-05
Publishing country	United States
Document type	Journal Article
ISSN	1932-1058
ISSN	1932-1058
DOI	10.1063/1.4907807
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Article ; Online: Pinched-flow hydrodynamic stretching of single-cells.

Dudani, Jaideep S / Gossett, Daniel R / Tse, Henry T K / Di Carlo, Dino

Lab on a chip

2013 Volume 13, Issue 18, Page(s) 3728–3734

Abstract: Reorganization of cytoskeletal networks, condensation and decondensation of chromatin, and other whole cell structural changes often accompany changes in cell state and can reflect underlying disease processes. As such, the observable mechanical ... ...

Abstract	Reorganization of cytoskeletal networks, condensation and decondensation of chromatin, and other whole cell structural changes often accompany changes in cell state and can reflect underlying disease processes. As such, the observable mechanical properties, or mechanophenotype, which is closely linked to intracellular architecture, can be a useful label-free biomarker of disease. In order to make use of this biomarker, a tool to measure cell mechanical properties should accurately characterize clinical specimens that consist of heterogeneous cell populations or contain small diseased subpopulations. Because of the heterogeneity and potential for rare populations in clinical samples, single-cell, high-throughput assays are ideally suited. Hydrodynamic stretching has recently emerged as a powerful method for carrying out mechanical phenotyping. Importantly, this method operates independently of molecular probes, reducing cost and sample preparation time, and yields information-rich signatures of cell populations through significant image analysis automation, promoting more widespread adoption. In this work, we present an alternative mode of hydrodynamic stretching where inertially-focused cells are squeezed in flow by perpendicular high-speed pinch flows that are extracted from the single inputted cell suspension. The pinched-flow stretching method reveals expected differences in cell deformability in two model systems. Furthermore, hydraulic circuit design is used to tune stretching forces and carry out multiple stretching modes (pinched-flow and extensional) in the same microfluidic channel with a single fluid input. The ability to create a self-sheathing flow from a single input solution should have general utility for other cytometry systems and the pinched-flow design enables an order of magnitude higher throughput (65,000 cells s(-1)) compared to our previously reported deformability cytometry method, which will be especially useful for identification of rare cell populations in clinical body fluids in the future.
MeSH term(s)	Biomechanical Phenomena/drug effects ; Cell Size/drug effects ; HeLa Cells ; Humans ; Hydrodynamics ; Jurkat Cells ; MCF-7 Cells ; Microfluidic Analytical Techniques/instrumentation ; Oxazoles/pharmacology ; Single-Cell Analysis ; Tetradecanoylphorbol Acetate/analogs & derivatives ; Tetradecanoylphorbol Acetate/pharmacology
Chemical Substances	12-O-tetradecanoylphorbol-1,3-acetate ; Oxazoles ; calyculin A (7D07U14TK3) ; Tetradecanoylphorbol Acetate (NI40JAQ945)
Language	English
Publishing date	2013-09-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2056646-3
ISSN	1473-0189 ; 1473-0197
ISSN (online)	1473-0189
ISSN	1473-0197
DOI	10.1039/c3lc50649e
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Article ; Online: Persistent organic pollutants in green sea turtles (Chelonia mydas) inhabiting two urbanized Southern California habitats.

Barraza, Arthur D / Komoroske, Lisa M / Allen, Camryn D / Eguchi, Tomoharu / Gossett, Rich / Holland, Erika / Lawson, Daniel D / LeRoux, Robin A / Lorenzi, Varenka / Seminoff, Jeffrey A / Lowe, Christopher G

Marine pollution bulletin

2020 Volume 153, Page(s) 110979

Abstract: Within Southern California, east Pacific green sea turtles (Chelonia mydas) forage year-round, taking advantage of diverse food resources, including seagrass, marine algae, and invertebrates. Assessing persistent organic pollutants (POP) in green turtle ... ...

Abstract	Within Southern California, east Pacific green sea turtles (Chelonia mydas) forage year-round, taking advantage of diverse food resources, including seagrass, marine algae, and invertebrates. Assessing persistent organic pollutants (POP) in green turtle aggregations in the Seal Beach National Wildlife Refuge (SBNWR, n = 17) and San Diego Bay (SDB, n = 25) can help quantify contamination risks for these populations. Blood plasma was analyzed for polychlorinated biphenyls (PCBs), organochlorinated pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs). PCBs and body size explained much of the separation of turtles by foraging aggregation in a principal component analysis. Turtles from SDB had significantly (p < 0.001) higher total PCBs than SBNWR turtles. Most PCBs detected in turtles were non-dioxin-like PCB congeners (153, 138, 99) that are associated with neurotoxicity. Recaptured turtles' POP levels changed significantly over time indicating significant variation in POP levels through time and space, even among adjacent foraging locations.
MeSH term(s)	Animals ; California ; Ecosystem ; Environmental Monitoring ; Organic Chemicals/metabolism ; Polychlorinated Biphenyls/metabolism ; Turtles/metabolism ; Water Pollutants, Chemical/metabolism
Chemical Substances	Organic Chemicals ; Water Pollutants, Chemical ; Polychlorinated Biphenyls (DFC2HB4I0K)
Language	English
Publishing date	2020-02-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2001296-2
ISSN	1879-3363 ; 0025-326X
ISSN (online)	1879-3363
ISSN	0025-326X
DOI	10.1016/j.marpolbul.2020.110979
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