Thomas Zangle

Thomas Zangle
University of Utah | UOU · Department of Chemical Engineering

28.47
 · 
PhD Mechanical Engineering
About
36
Research items
1,356
Reads
606
Citations
Research Experience
Aug 2016
University of Utah
Position
  • Assistant Professor
Apr 2014 - Aug 2016
Feb 2010 - Apr 2014
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Research
Research items (36)
Article
Microfluidic devices are widely used for biomedical applications based on microscopy or other optical detection methods. However, the materials commonly used for microfabrication typically have a high refractive index relative to water, which can create artifacts at device edges and limit applicability to applications requiring high-precision imagi...
Article
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Rapid antibody production in response to invading pathogens requires the dramatic expansion of pathogen-derived antigen-specific B lymphocyte populations. Whether B cell population dynamics are based on stochastic competition between competing cell fates, as in the development of competence by the bacteriumBacillus subtilis, or on deterministic cel...
Article
Somatic cell reprogramming to pluripotency requires an immediate increase in cell proliferation and reduction in cell size. It is unknown whether proliferation and biomass controls are similarly coordinated with early events during the differentiation of pluripotent stem cells (PSCs). This impasse exists because PSCs grow in tight clusters or colon...
Article
Current methods of optimizing electroosmotic (EO) pump performance include reducing pore diameter and reducing ionic strength of the pumped electrolyte. However, these approaches each increase the fraction of total ionic current carried by diffuse electric double layer (EDL) counterions. When this fraction becomes significant, concentration polariz...
Article
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In this tutorial review aimed at researchers using nanofluidic devices, we summarize the current state of theoretical and experimental approaches to describing concentration polarization (CP) in hybrid microfluidic-nanofluidic systems. We also analyze experimental results for these systems and place them in the context of recent theoretical develop...
Article
The use of microfluidic devices has emerged as a defining tool for biomedical applications. When combined with modern microscopy techniques, these devices can be implemented as part of a robust platform capable of making simultaneous complementary measurements. The primary challenge created by the combination of these two techniques is the mismatch...
Article
We report the development of High Speed Live Cell Interferometry (HSLCI), a new multi-sample, multi-drug testing platform for directly measuring tumor therapy response via real-time optical cell biomass measurements. As a proof-of-concept, we show that HSLCI rapidly profiles changes in biomass in BRAF inhibitor (BRAFi) sensitive, parental melanoma...
Article
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Standard algorithms for phase unwrapping often fail for interferometric quantitative phase imaging (QPI) of biological samples due to the variable morphology of these samples and the requirement to image at low light intensities to avoid phototoxicity. We describe a new algorithm combining random walk-based image segmentation with linear discrimina...
Article
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The equal partitioning of cell mass between daughters is the usual and expected outcome of cytokinesis for self-renewing cells. However, most studies of partitioning during cell division have focused on daughter cell shape symmetry or segregation of chromosomes. Here, we use live cell interferometry (LCI) to quantify the partitioning of daughter ce...
Article
Cell mass, volume and growth rate are tightly controlled biophysical parameters in cellular development and homeostasis, and pathological cell growth defines cancer in metazoans. The first measurements of cell mass were made in the 1950s, but only recently have advances in computer science and microfabrication spurred the rapid development of preci...
Article
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Cancer cell proliferation relies on the ability of cancer cells to grow, transition through the cell cycle, and divide. To identify novel chemical probes for dissecting the mechanisms governing cell cycle progression and cell division, and for developing new anti-cancer therapeutics, we developed and performed a novel cancer cell-based high-through...
Article
Adoptive immunotherapies against cancer, in which cytotoxic, CD8+ T cells engineered to express T cell receptors (TCRs) targeting cancer-associated antigens are transplanted into a patient, have shown dramatic promise in clinical trials. A major impediment to the widespread use of this technique for treatment of diverse cancers is the lack of a fas...
Article
Full-text available
Existing approaches that quantify cytotoxic T cell responses rely on bulk or surrogate measurements which impede the direct identification of single activated T cells of interest. Single cell microscopy or flow cytometry methodologies typically rely on fluorescent labeling, which limits applicability to primary cells such as human derived T lymphoc...
Data
Intensity images of cells on the interferometer stage after 18 h of imaging showing typical target cell conditons. Left column shows the full image frame, the right column shows a subset of the full image frame. (A)–(D) M202 target cells plated with F5 TCR transduced, CD8+ T cells showing nearly complete death of target cells. For comparison, (A) a...
Data
Four panel video showing intensity images, mass distribution images, and mass vs. time of a target M202 cell being killed by a cytotoxic T cell (CD8+, F5 TCR transduced) over the course of 5 hours of observation by LCI. (MOV)
Data
Averaged, normalized mass versus time plots for control target cell growth conditions showing robust growth on the LCI stage, and specificity of T cell mediated cytotoxicity. (A) Unaffected M202 cells (n = 632) during treatment with F5 TCR transduced, CD8+ T cells. (B) M202 cells (n = 117) prior to treatment with F5 TCR transduced, CD8+ T cells. (C...
Data
(A)–(J). Mass versus time plots for CTLs and corresponding target cells, as in Figure 4A. t = 0 h is the point at which the target cell detaches from the substrate at the beginning of cell death. CTL + target cell refers to total mass of both cells in frames where they could not be measured individually, typically due to overlap between the CTL and...
Data
(A) Mass and (B) area histograms for activated and unresponsive T cells, relative to control experiments. Activated = activated/cytotoxic F5 TCR transduced T cells, 116 cells, n = 3 experiments. Unactivated = unactivated/unresponsive F5 TCR transduced T cells, 359 cells, n = 3 experiments. F5neg = untransduced F5 TCR negative T cells plated with M2...
Data
Averaged, normalized mass versus time for unresponsive T cells showing steady growth on the LCI stage. (A) Unresponsive F5 TCR transduced CD8+ T cells (n = 101) plated with M202 target cells. (B) Untransduced CD8+ T cells (n = 146) plated with M202 target cells. (C) F5 TCR transduced CD8+ T cells (n = 950) plated with antigen-irrelevant, PC-3 prost...
Article
Despite the potential high impact of human pluripotent stem cell (hPSC) research in developmental biology, cancer biology, and regenerative medicine, surprisingly little is known about how hPSCs grow, divide, and respond to their environment. In this talk, we will introduce live cell interferometery (LCI) as a new, biophysical measurement approach...
Article
Full-text available
Live cell mass profiling is a promising new approach for rapidly quantifying responses to therapeutic agents through picogram-scale changes in cell mass over time. A significant barrier in mass profiling is the inability of existing methods to handle pleomorphic cellular clusters and clumps, which are more commonly present in patient-derived sample...
Article
Despite much attention to the regulation of genetic material partitioning during cell division, relatively little is known about the partitioning of cell mass, an essential outcome of successful cytokinesis. Recent work suggests that mispartitioning of cellular contents during division may constitute a form of epigenetic memory, however, convention...
Article
Live Cell Interferometry (LCI) is a real time imaging technology that is extremely well suited to capture motion on the micro- and even nano-scale, with a temporal dynamic range and field of view that far exceeds scanning probe techniques. We will describe the development and application of LCI for rapid, real-time quantification of single-cell mas...
Article
A central question in cancer therapy is how individual cells within a population of tumor cells respond to drugs designed to arrest their growth. However, the absolute growth of cells, their change in physical mass, whether cancerous or physiologic, is difficult to measure directly with traditional techniques. Here, we develop live cell interferome...
Article
We extend the analytical theory of propagating concentration polarization (CP) to describe and compare the effects of constant-voltage versus constant-current conditions on the transient development of CP enrichment and depletion zones. We support our analysis with computational and experimental results. We find that at constant voltage, enrichment...
Article
Porous structures with submicron pore diameters and low ionic strength electrolytes yield more efficient electroosmotic (EO) pumps. For these conditions, however, electric double layers may carry a substantial portion of ionic current, creating an imbalance between current carried by anions versus cations. This leads to the formation of net neutral...
Article
We develop two models to describe ion transport in variable-height micro- and nanochannels. For the first model, we obtain a one-dimensional (unsteady) partial differential equation governing flow and charge transport through a shallow and wide electrokinetic channel. In this model, the effects of electric double layer (EDL) on axial transport are...
Article
We present results of a combined computational and experimental study of the propagation of concentration polarization (CP) zones in a microchannel-nanochannel system. Our computational model considers the combined effects of bulk flow, electromigration, and diffusion and accurately captures the dynamics of CP. Using wall charge inside the nanochan...
Conference Paper
Full-text available
Electroosmotic (EO) pumps can generate relatively high pressure and flow rate using no moving parts and small package volumes. Pumps with one micron (and smaller) pore diameters are promising for applications requiring high flow rate per power, such as drug delivery systems. We here show that such EO pumps exhibit significant concentration polariza...
Conference Paper
Nanopores offer the potential for label-free analysis of individual proteins and low cost DNA sequencing. In order to design and evaluate nanopore devices, an understanding of nanopore electrokinetic transport is crucial. However, most studies of nanopore electrokinetic transport have neglected the effects of concentration polarization (CP) in the...
Conference Paper
Recent advances in fabrication methods allow us to study and leverage the unique flow regimes offered by nano-scale fluidic channels, [1–3] and recent work suggests that the physics of microchannel/nanochannel interfaces present opportunities for novel methods of sample preconcentration and analysis. [4–6] In nanochannels, channel height is of the...