A Novel Encoded Particle Technology that Enables Simultaneous Interrogation of Multiple Cell Types

Beske, Oren; Guo, Jinjiao; Li, Jianren; Bassoni, Daniel L.; Bland, Kimberly S.; Marciniak, Holly; Zarowitz, Mike; Temov, Vladimir; Ravkin, Ilya; Goldbard, Simon

doi:10.1177/1087057103260088

Cited by 34 publications

(25 citation statements)

References 25 publications

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“…That is, if we assay ten cell lines in the same reaction volume that is typically used for a single cell line, that volume becomes ten times more efficient. We have proven repeatedly that cell lines multiplexed on CellCards and grown independently in plates behave indistinguishably, provided they are at the same level of confluency 6 .…”

Section: Introductionmentioning

confidence: 92%

Multiplexed cell analysis on CellCards for drug discovery

Ravkin

Temov

Nelson

et al. 2004

Microarrays and Combinatorial Techniques: Design, Fabrication, and Analysis II

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The desire to obtain more biologically relevant data is expanding the use of cell-based assays in drug discovery. These assays are performed and analyzed in ever more sophisticated ways (e.g. high content screening) that allow the collection of multiparametric information about cells affected by the screened compounds. The driver for these developments is the desire to increase data quality and density and reduce the use of valuable reagents and time.Here we describe an approach that adds a new dimension to the data quality/quantity mix by simultaneously analyzing several cell types in the same microplate well. The system is based on the use of encoded carriers (CellCards®) that permit the reading and analysis of cellular responses, and at the same time allow decoding and the attribution of these responses to the appropriate cell line. CellCards are rectangular particles with an expandable color barcode and a transparent section upon which cells can be grown and imaged for cellular readout. Before performing the assay, each cell line is grown on a different class of CellCards. CellCards, with attached cells, are mixed and dispensed into a microtiter plate where the assay is performed. Next the plates are imaged, decoded and the cells associated with each CellCard class are analyzed.Multiplexing cell lines allows assay controls and data normalization within each well, reducing well-to-well variability. It also allows the simultaneous interrogation of multiple targets and thus concurrent potency and selectivity screening. This may significantly reduce the time required to take a compound from primary screening into the clinic.

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Section: Introductionmentioning

confidence: 92%

Multiplexed cell analysis on CellCards for drug discovery

Ravkin

Temov

Nelson

et al. 2004

Microarrays and Combinatorial Techniques: Design, Fabrication, and Analysis II

Self Cite

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“…These issues, together with debatable biocompatibility, limit the applications of the barcode particles in multiple-cell research. [ 209,211 ] To solve these problems, biocompatible biomaterials and silica hybrid PCBs were suggested for cell culture ( Figure 18 ). [ 212 ] The size of the PCBs can be adjusted by microfl uidics to be suitable for cell culture.…”

Section: Cell Culturementioning

confidence: 99%

Microfluidic Synthesis of Barcode Particles for Multiplex Assays

Zhao

Cheng

Shang

et al. 2014

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The increasing use of high-throughput assays in biomedical applications, including drug discovery and clinical diagnostics, demands effective strategies for multiplexing. One promising strategy is the use of barcode particles that encode information about their specific compositions and enable simple identification. Various encoding mechanisms, including spectroscopic, graphical, electronic, and physical encoding, have been proposed for the provision of sufficient identification codes for the barcode particles. These particles are synthesized in various ways. Microfluidics is an effective approach that has created exciting avenues of scientific research in barcode particle synthesis. The resultant particles have found important application in the detection of multiple biological species as they have properties of high flexibility, fast reaction times, less reagent consumption, and good repeatability. In this paper, research progress in the microfluidic synthesis of barcode particles for multiplex assays is discussed. After introducing the general developing strategies of the barcode particles, the focus is on studies of microfluidics, including their design, fabrication, and application in the generation of barcode particles. Applications of the achieved barcode particles in multiplex assays will be described and emphasized. The prospects for future development of these barcode particles are also presented.

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“…Furthermore, with the advent of high content and multiplex screening more detailed mechanistic characterisation can also be achieved directly at primary HTS using functional assays. For example, several signalling pathways can be measured [47], receptor desensitisation / internalisation events can be assessed [19,20] and cellular cytoxicity can be evaluated in parallel to target screening [48]. This additional information enables project teams to make educated, rapid decisions about which compounds are the best to follow up, a fact that provides significant advantage to cell-based assays in the drug discovery process.…”

Section: Acknowledgementsmentioning

confidence: 99%

G-Protein Coupled Receptor Assays: To Measure Affinity or Efficacy that is the Question

Williams

Sewing²

2005

CCHTS

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Cell-based assays have always played an important role in the pharmaceutical industry, providing information about the functional effects of compounds. These functional assays have traditionally accompanied facile biochemical high throughput screening programmes, being applied as secondary assays in the later stages of lead development. However, with the disappointing reality that there is not likely to be a plethora of novel, druggable targets in the post-genomic era, the role of cell-based assays in drug discovery is beginning to change. Competition to develop the "best" agents for well established targets and find more effective ways of identifying "novel" agents is driving the industry towards a "quality" versus "quantity" approach. Advances in genetic engineering, automation compatible functional assay technologies and the introduction of more sophisticated robotic systems, have facilitated the application of cell-based assays to primary screening. However, despite some apparent success to move these assays into the routine "toolbox" for high throughput screening, certain preconceptions and concerns about cell-based assays persist and the subject remains a topic of much debate. Here we use examples from the screening portfolio at Pfizer, Sandwich, to discuss the practical and theoretical considerations of employing cell-based assays in HTS with a focus on G-protein coupled receptors.

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A Novel Encoded Particle Technology that Enables Simultaneous Interrogation of Multiple Cell Types

Cited by 34 publications

References 25 publications

Multiplexed cell analysis on CellCards for drug discovery

Multiplexed cell analysis on CellCards for drug discovery

Microfluidic Synthesis of Barcode Particles for Multiplex Assays

G-Protein Coupled Receptor Assays: To Measure Affinity or Efficacy that is the Question

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