Next Generation Ligand Binding Assays—Review of Emerging Technologies’ Capabilities to Enhance Throughput and Multiplexing

Mora, Johanna; Chunyk, Allison G.; Dysinger, Mark; Purushothama, Shobha; Ricks, Claude; Österlund, Karolina; Theobald, Valerie

doi:10.1208/s12248-014-9660-1

Cited by 31 publications

(14 citation statements)

References 12 publications

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“…The binding between a ligand and its receptor is the main area of research in several biological related disciplines. Ligand-receptor binding is ubiquitous in many biological processes, including immune reactions, signaling, opening of ion channels and gene activity [ 1 – 4 ]. In the pharmaceutical industry, around 70% of the total sales of drugs to treat cancer [ 5 ] and autoimmune diseases [ 6 ] are therapies based on the binding of antibodies (the ligands) to specific receptors.…”

Section: Introductionmentioning

confidence: 99%

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Behavior of ligand binding assays with crowded surfaces: Molecular model of antigen capture by antibody-conjugated nanoparticles

2017

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Ligand-receptor binding is of utmost importance in several biologically related disciplines. Ligand binding assays (LBA) use the high specificity and high affinity of ligands to detect, target or measure a specific receptors. One particular example of ligand binding assays are Antibody conjugated Nanoparticles (AcNPs), edge-cutting technologies that are present in several novel biomedical approaches for imaging, detection and treatment of diseases. However, the nano-confinement in AcNPs and LBA nanostructures introduces extra complexity in the analysis of ligand-receptor equilibriums. Because antibodies are large voluminous ligands, the effective affinity in AcNPs is often determined by antibody orientation and surface coverage. Moreover, antibodies have two binding sites introducing an extra ligand-receptor binding equilibrium. As consequence of all this, experimental or theoretical studies providing a guidelines for the prediction of the binding behavior in AcNPs are scarce. In this work, we present a set of theoretical calculations to shed light into the complex binding behavior of AcNPs and its implications in biomedical applications. To investigate the ligand-receptor binding on AcNPs, we have used a molecular theory that predicts the probability of different molecular conformations of the system depending on the local environment. We have considered two different pathways for designing these devices: covalently conjugated antibodies and streptavidin-biotin conjugated antibodies. We also explore the effects of surface coverage, bulk concentrations, nanoparticle size and antibody-antigen affinity. Overall, this work offers a series of theoretical predictions that can be used as a guide in the design of antibody conjugated nanoparticles for different applications.

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Section: Introductionmentioning

confidence: 99%

“…Due to these characteristics the biomedical research field has introduce several techniques that exploit ligand-receptor interactions. In particular, we can mention ligand-binding assays (LBA) that use ligands to detect, to target or to measure a specific receptor [ 1 – 3 ].…”

Section: Introductionmentioning

confidence: 99%

Behavior of ligand binding assays with crowded surfaces: Molecular model of antigen capture by antibody-conjugated nanoparticles

2017

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“…Mass cytometry : Mass cytometry is a variation of flow cytometry in which antibodies are labeled with heavy metal ion tags, rather than fluorochromes, and has the potential to replace conventional flow cytometry [56]. Readout is by time-of-flight mass spectrometry.…”

Section: Current Status Of Genomic and Related Informationmentioning

confidence: 99%

Integrating cancer genomic data into electronic health records

2016

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The rise of genomically targeted therapies and immunotherapy has revolutionized the practice of oncology in the last 10–15 years. At the same time, new technologies and the electronic health record (EHR) in particular have permeated the oncology clinic. Initially designed as billing and clinical documentation systems, EHR systems have not anticipated the complexity and variety of genomic information that needs to be reviewed, interpreted, and acted upon on a daily basis. Improved integration of cancer genomic data with EHR systems will help guide clinician decision making, support secondary uses, and ultimately improve patient care within oncology clinics. Some of the key factors relating to the challenge of integrating cancer genomic data into EHRs include: the bioinformatics pipelines that translate raw genomic data into meaningful, actionable results; the role of human curation in the interpretation of variant calls; and the need for consistent standards with regard to genomic and clinical data. Several emerging paradigms for integration are discussed in this review, including: non-standardized efforts between individual institutions and genomic testing laboratories; “middleware” products that portray genomic information, albeit outside of the clinical workflow; and application programming interfaces that have the potential to work within clinical workflow. The critical need for clinical-genomic knowledge bases, which can be independent or integrated into the aforementioned solutions, is also discussed.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0371-3) contains supplementary material, which is available to authorized users.

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“…Other emerging systems include Single molecule array (Simoa ™ ), Optimiser ™ , SQIDLite ™ , and iLite ™ . These technologies as well as CyTOF have been evaluated and comprehensively reviewed elsewhere (Mora et al 2014). …”

Section: High Content Image Informatics For Timely Screening and Cellmentioning

confidence: 99%

Convergence of Highly Resolved and Rapid Screening Platforms with Dynamically Engineered, Cell Phenotype-Prescriptive Biomaterials

2016

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Biophysical and biochemical cues from the cellular microenvironment initiate intracellular signaling through cellular membrane receptors and trigger specific cell developmental programs. Extracellular substrates and matrix scaffolds engineered to mimic cell’s native physiological environment must incorporate the multifactorial parameters (composition, micro and nanoscale organization and topography) of the extracellular matrix as well as the dynamic nature of the matrix. The design of such engineered biomaterials is challenged by the inherent complexity and dynamic nature of the cell-extracellular matrix reciprocity, while the validation of robust microenvironments requires a deeper, higher content phenotypic resolution of cell-matrix interactions alongside a rapid screening capability. To this end, high-throughput platforms are integral to facilitating the screening and optimization of complex engineered microenvironments for directing desired cell developmental pathway. This review highlights the recent advances in biomaterial platforms that present dynamic cues and enable high throughput screening of cell’s response to a combination of micro-environmental factors. We also address some newer techniques involving high content image informatics to elucidate emergent cellular behaviors with a focus on stem cell regenerative endpoints.

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Next Generation Ligand Binding Assays—Review of Emerging Technologies’ Capabilities to Enhance Throughput and Multiplexing

Cited by 31 publications

References 12 publications

Behavior of ligand binding assays with crowded surfaces: Molecular model of antigen capture by antibody-conjugated nanoparticles

Behavior of ligand binding assays with crowded surfaces: Molecular model of antigen capture by antibody-conjugated nanoparticles

Integrating cancer genomic data into electronic health records

Convergence of Highly Resolved and Rapid Screening Platforms with Dynamically Engineered, Cell Phenotype-Prescriptive Biomaterials

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