Deirdre R Meldrum

Arizona State University | ASU

A two-photon absorbing (2PA) red emitter group was chemically conjugated onto amphiphilic poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) copolymers, and further grafted with cyclo(Arg-Gly-Asp) (cRGD) peptide to form micelle 1. Micelle 1 with cRGD targeting groups were used for targeted bioimaging. For comparison, micelle 2 without the...

We present a new approach for three-dimensional (3D) live single-cell imaging with isotropic sub-micron spatial resolution using fluorescence computed tomography (fCT). A thin, highly inclined and laminated optical (HILO) sheet of light is used for fluorescence excitation in live single cells that are rotated around an axis perpendicular to the opt...

Escalating concerns about CO2 emission from fossil fuels utilization and environmental pollution from fossil-derived plastic waste call for the sustainable production and utilization of renewable biodegradable plastic materials. Polyhydroxyalkanoates (PHAs) are biodegradable and biocompatible thermoplastics with thermal and mechanical properties co...

Scaffolds generated from naturally occurring and synthetic polymers have been investigated in several applications because of their biocompatibility and tunable chemo‐mechanical properties. Existing methods for generation of 3D polymeric scaffolds typically cannot be parallelized, suffer from low throughputs, and do not allow for quick and easy rem...

Functional and genomic heterogeneity of individual cells are central players in a broad spectrum of normal and disease states. Our knowledge about the role of cellular heterogeneity in tissue and organism function remains limited due to analytical challenges one encounters when performing single cell studies in the context of cell-cell interactions...

Precise spatial positioning and isolation of mammalian cells is a critical component of many single cell experimental methods and biological engineering applications. Although a variety of cell patterning methods have been demonstrated, many of these methods subject cells to high stress environments, discriminate against certain phenotypes, or are...

In this paper we report synthesis and characterization of a novel multi-modality (MRI/Fluorescence) probe for pH sensing and imaging. A multifunctional polymer was derived from poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA) and integrated with a naphthalimide-based-ratiometric fluorescence probe and a gadolinium -1,4,7,10-tetraazacyclododecane-1,...

Quantitative three-dimensional (3D) computed tomography (CT) imaging of living single cells enables orientation-independent morphometric analysis of the intricacies of cellular physiology. Since its invention, x-ray CT has become indispensable in the clinic for diagnostic and prognostic purposes due to its quantitative absorption-based imaging in t...

We report on a method for rotating single mammalian cells about an axis perpendicular to the optical system axis through the imaging plane using dynamic holographic optical tweezers (HOTs). Two optical traps are created on the opposite edges of a mammalian cell and are continuously transitioned through the imaging plane along the circumference of t...

Driven by an increasing number of studies demonstrating its relevance to a broad variety of disease states, the bioenergy production phenotype has been widely characterized at the bulk sample level. Its cell-to-cell variability, a key player associated with cancer cell survival and recurrence, however, remains poorly understood due to ensemble aver...

Adhesion properties of the four BE cell types. Differential adhesion of the four studied cell types to the used ECM proteins and their mixture. The formulation of the mixture was the same as used in the rest of the study (Materials and methods). (TIF)

Intercellular interactions play a central role at the tissue and whole organism level modulating key cellular functions in normal and disease states. Studies of cell-cell communications are challenging due to ensemble averaging effects brought about by intrinsic heterogeneity in cellular function which requires such studies to be conducted with sma...

Functional and molecular cell-to-cell variability is pivotal at the cellular, tissue and whole-organism levels. Yet, the ultimate goal of directly correlating the function of the individual cell with its biomolecular profile remains elusive. We present a platform for integrated analysis of functional and transcriptional phenotypes in the same singl...

A new two-layer sensor film was constructed for sensing glucose based on glucose oxidase and oxygen sensing material. The first layer of film containing the oxygen sensor and intra-reference material was polymerized, then the second layer of glucose oxidase and glutaraldehyde was formed on the oxygen sensor layer. The two-layer sensor film has a re...

Quantitative 3D imaging of live single tumor cells enables direct insights into the intricacies of cellular machinery while offering new ways of assessing intercellular variability. Since its invention, X-ray computed tomography has been indispensable in the clinic for cancer diagnostic and prognostic purposes due to its quantitative manner of imag...

This paper presents three different microfabrication technologies for manufacturing out-of-plane, flat-bottomed, undercut trapezoidal structures for generating a fluidic microscale vortex (microvortex). The first method is based on anisotropic silicon etching and a 'sandwich' UV polymer casting assembly; the second method uses a backside diffuser p...

Gene expression studies which utilize lipopolysaccharide (LPS)-stimulated macrophages to model immune signaling are widely used for elucidating the mechanisms of inflammation-related disease. When expression levels of target genes are quantified using Real-Time quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), they are analyze...

This work describes an enhancement to the loop-mediated isothermal amplification (LAMP) reaction which results in improved performance. Enhancement is achieved by adding a new set of primers to conventional LAMP reactions. These primers are termed ‘Swarm primers’ based on their relatively high concentration and their ability to create new amplicons...

In carcinogenesis, intercellular interactions within and between cell types are critical but remain poorly understood. We present a study on intercellular interactions between normal and premalignant epithelial cells and their functional relevance in the context of premalignant to malignant progression in Barrett’s esophagus. Using whole transcript...

Migration is a fundamental cellular behavior that plays an indispensable role in development and homeostasis, but can also contribute to pathology such as cancer metastasis. Due to its relevance to many aspects of human health, the ability to accurately measure cell migration is of broad interest, and numerous approaches have been developed. One of...

The histone deacetylase (HDAC) inhibitor vorinostat has received significant attention in recent years as an ‘epigenetic’ drug used to treat solid tumors. However, its mechanisms of action are not entirely understood, particularly with regard to its interaction with the aberrations in 3D nuclear structure that accompany neoplastic progression. We i...

Intercellular heterogeneity is pivotal in carcinogenesis and tumor development and plays a central role in advanced metastatic disease, therapeutic resistance, and recurrence at the cellular, tissue and whole organism levels. Rapid advances in single-cell analysis technologies have enabled unprecedented insights into cellular machinery. Yet, the ul...

An ideal fluorescent dye for staining cell organelles should have multiple properties including specificity, stability, biocompatibility and a large Stokes shift. Tuneable photophysical properties enable 1,8-naphthalimide to be an excellent fluorophore in biomedical applications. Many naphthalimide derivatives have been developed into drugs, sensor...

Extracellular pH has a strong effect on cell metabolism and growth. Precisely detecting extracellular pH with high throughput is critical for cell metabolism research and fermentation applications. In this research, a series of ratiometric fluorescent pH sensitive polymers are developed and the ps-pH-neutral is characterized as the best one for exc...

The inflammasome is a caspase-1-activating complex that is implicated in a growing number of acute and chronic pathologies. Interest has increased in identifying small molecular inhibitors of inflammasome signaling because of its role in clinically relevant diseases. It was recently reported that the protein tyrosine kinase, Syk, regulates pathogen...

P2X7 purinergic receptor engagement with extracellular ATP induces transmembrane potassium and calcium flux resulting in assembly of the NLRP3 inflammasome in LPS-primed macrophages. The role of potassium and calcium in inflammasome regulation is not well understood, largely due to limitations in existing methods for interrogating potassium in real...

Restriction digestion of foreign DNA is one of the key biological barriers against genetic transformation in microorganisms. To establish a high-efficiency transformation protocol in the model cyanobacterium, Synechocystis sp. strain PCC 6803 (Synechocystis 6803), we investigated the effects of premethylation of foreign DNA on the integrative trans...

Regulation of intracellular potassium (K(+) ) concentration plays a key role in metabolic processes. So far, only a few intracellular K(+) sensors have been developed. The highly selective fluorescent K(+) sensor KS6 for monitoring K(+) ion dynamics in mitochondria was produced by coupling triphenylphosphonium, borondipyrromethene (BODIPY), and tri...

Cell-cell communication plays a central role in cellular function under normal and diseased conditions. In cancer, intercellular interactions are highly complex and remain poorly understood, particularly with respect to the early events leading to the transformation from benign to malignant phenotypes. In early stages of carcinogenesis, normal and...

Nucleic acid extraction is a necessary step for most genomic/transcriptomic analyses, but it often requires complicated mechanisms to be integrated into a lab-on-a-chip device. Here, we present a simple, effective configuration for rapidly obtaining purified RNA from low concentration cell medium. This Total RNA Extraction Droplet Array (TREDA) uti...

We present a photolithography-based method for micropatterning cells into microwells for metabolic profiling. The method is to seed the cells inside the microwells by functionalizing the PEG on the surface. The result is consistent with Poisson distribution and has shown high selectivity of cells seeding in microwells compared to other random seedi...

We present a multi-step photo-polymerization process for patterning triple fluorescence sensor arrays on fused silica chips. The sensor arrays can hermetically seal with microwell arrays containing single live cells for simultaneous measurements of metabolic parameters, such as oxygen consumption rate (OCR) and extracellular acidification rate (ECA...

The three-dimensional (3D) structure of the cell and its nucleus is intricately associated with cellular function. Aberrations and heterogeneity in cellular and nuclear morphology serve as diagnostically important cues to identify malignant transformation. However, current cytopathology practice is predominantly based on a qualitative, 2D assessmen...

The field of single-cell analysis has gained a significant momentum over the last decade. Separation and isolation of individual cells is an indispensable step in almost all currently available single-cell analysis technologies. However, stress levels introduced by such manipulations remain largely unstudied. We present a method for minimally invas...

The present invention relates to an optical fluorescence dual sensor comprising a probe for sensing pH, a probe for sensing oxygen, an intra-reference probe and a matrix. The present invention also relates to methods of preparing an optical fluorescence dual sensor and methods of using them.

The glucose metabolism level reflects cell proliferative status. A polymeric glucose ratiometric sensor comprising poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and poly[2-(methacryloyloxy)ethyl]trimethylammonium chloride (PMAETMA) was synthesized. Cellular internalization and glucose response of the polymer within HeLa cells were investigated.

Heterogeneity within cell populations is relevant to the onset and progression of disease, as well as development and maintenance of homeostasis. Analysis and understanding of the roles of heterogeneity in biological systems require methods and technologies that are capable of single cell resolution. Single cell gene expression analysis by RT-qPCR...

Abstract Populations of bacterial cells that grow under the same conditions and/or environments are often considered to be uniform and thus can be described by ensemble average values of their physiologic, phenotypic, genotypic or other parameters. However, recent evidence suggests that cell-to-cell differences at the gene expression level could be...

Core-shell microgels containing sensors/dyes in a matrix were fabricated by two-stage free radical precipitation polymerization method for ratiometric sensing/imaging. The microgels composing of poly(N-isopropylacrylamide) (PNIPAm) shell exhibits a low critical solution temperature (LCST), underwent an entropically driven transition from a swollen...

This paper presents a microfluidic device for colorimetric loop-mediated isothermal amplification (LAMP) detection based on hydroxynapthol blue (HNB), long optical pathlength reaction wells, and two-phase liquid loading into a novel array geometry. We show that an inexpensive camera can be used with diffuse illumination to detect colorimetric chang...

We present a method to stably rotate cells about a rotation axis perpendicular to the imaging axis, using a combination of hydrodynamic microvortex flow and optical trapping on a microfluidic chip. We present theoretical simulations, fabrication, system setup, rotation imaging, and data analysis. A tilted backside exposure technique was used to fab...

This paper presents the design and experimental results of a novel microchip that examines gene expression of single marine diatoms with a streamlined operation. To our knowledge, it is the first microfluidic device that integrates a streamlined process to analyze individual living diatoms that are protected within the silica frustule structures. T...

The water body underlying the photic zone in oceans represents the largest water mass on earth (comprising 1.3×1018 m3), and is also the largest aqueous habitat for various microorganisms. This realm differs distinctly from the photic zone, in terms of its relatively lower temperature (approximately 2~4°C), higher pressure and richer inorganic nutr...

Caspase-1, the cysteine protease responsible for processing the potent pro-inflammatory cytokines Interleukin-1β (IL-1β) and IL-18, is a central enzyme in a variety of inflammatory conditions such as sepsis and septic shock. In vitro evidence suggests that there are unknown factors that lead to either resistance or susceptibility to caspase-1-depen...

Barrett’s esophagus arises as the result of gastro-esophageal reflux disease (GERD) and is characterized by intestinal metaplasia of the esophageal epithelium. The condition is of particular significance in that it confers an approximate 30-fold increase in the risk of adenocarcinoma. However, less than 5% of Barrett’s cases progress to esophageal...

TNFα-related apoptosis-inducing ligand (TRAIL) induces death selectively in cancer cells. However, subpopulations of cancer cells are either resistant to or can develop resistance to TRAIL-induced death. As a result, strategies that overcome this resistance are currently under investigation. We have recently identified several US FDA-approved drugs...

We present the design, fabrication and characterization of multiple micro-pocket lid arrays used in live single cell metabolic analysis. In previous work we reported a platform for quantifying single cell oxygen consumption rates realized using a fused silica deep wet etching process. Here we extend that work to a dual-depth wet etching process for...

Cellular heterogeneity plays a pivotal role in a variety of functional processes in vivo including carcinogenesis. However, our knowledge about cell-to-cell diversity and how differences in individual cells manifest in alterations at the population level remains very limited mainly due to the lack of appropriate tools enabling studies at the single...

Scaffolded DNA origami, a versatile method to construct high yield selfassembled DNA nanostructures, has been investigated to develop water-soluble nanoarrays for label free RNA detection, drug delivery, molecular positioning and recognition, and spatially ordered catalysis of single molecule chemical reactions. Its attributes that facilitate these...

Although emerging evidence indicates that deep-sea water contains an untapped reservoir of high metabolic and genetic diversity, this realm has not been studied well compared with surface sea water. The study provided the first integrated meta-genomic and -transcriptomic analysis of the microbial communities in deep-sea water of North Pacific Ocean...