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The Untapped Potential in Live Cell Imaging (Technical Insights)

  • December 2013
  • -
  • Frost & Sullivan
  • -
  • 60 pages

Improved cellular dynamics in disease diagnostic and drug discovery

This research service is aimed at delivering an overview of the technologies for live cell imaging. Recent developments and trends in the industry have also been captured in this research service. This study provides snapshot of the technologies for live cell imaging, highlights of some of the key innovations in live cell imaging platforms and of some recent developments in in vitro / in vivo live cell imaging across different disease segments, key technical and business challenges for live cell imaging, key technical and business drivers that are fuelling success in this market, potential areas of application of live cell imaging, focusing on disease areas in which live cell imaging can find increased application and is primed for growth.

Executive Summary and Scope of the Research

An in-depth understanding of complex cellular dynamics that includes processes such as cell migration, morphological changes of cells, organs or whole animals, and physiological events in living specimens in real time constitutes an essential stage in the exploration of biological processes. Live cell imaging allows investigation into the process dynamics of living cells in real time by providing spatial and temporal information about dynamic events in single cells in situ cellular networks and in vivo whole organisms.

Furthermore, in recent years, live cell imaging has been enriched by advances in electronics, optics, and molecular biology, making this technology more accessible for life scientists. In course of the past decade, with the advent of omics technologies on one hand, and nanotechnologies on the other, commercially available lab-on-a-chip microfluidics systems have evolved to offer novel solutions for the analysis of cells, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins. The combination of these systems with microscopic imaging platforms to study biological material or to view cell morphology has been successful. Indeed, driven by the latest innovations in omics-based technologies and personalized medicine approaches, these platforms are beginning to be adopted into mainstream medicine, leading to new opportunities in life sciences research and clinical applications.

This research service, titled “The Untapped Potential in Live-Cell Imaging,” is aimed at delivering an overview of the technologies for live cell imaging. Recent developments and trends in the industry have also been captured in this research service. This study provides:
• Snapshot of the technologies for live cell imaging
• Highlights of some of the key innovations in live cell imaging platforms and of some recent developments in in vitro and in vivo live cell imaging across different disease segments
• Key technical and business challenges for live cell imaging
• Key technical and business drivers that are fuelling success in this market
• Potential areas of application of live cell imaging, focusing on disease areas in which live cell imaging can find increased application and is primed for growth.

Research Methodology

Primary Research
• Engineers
• CTOs/CEOs/CIOs
• Technical Architects
• Research Heads
• Strategic Decision Makers
• Technology Policy Heads

Secondary Research
• Technology Journals
• Periodicals
• Market Research Reports
• Technology Policy Information Sites
• Internal Databases
• Thought Leader Briefings

Technology Capabilities

• Live cell imaging constitutes a significant technology for disease diagnostics and the drug discovery process.
• Currently available technologies include cell-based assays (live cell-based assay systems) and molecular models (high resolution imaging systems)
• Live cell imaging enables investigating process dynamics in living cells in real time, by providing spatial and temporal information about dynamic events in single cells, in in situ cellular networks and in vivo whole organisms.

• Latest innovations in omics-based technologies and personalized medicine approaches have led to new possibilities in both life sciences research and clinical applications.
• The live cell imaging field is being enhanced by recent advancements in optical systems and fluorescent tools.
• The urgency to understand biological dynamics has spurred the interest in visualizing cellular events in living cells and organisms.
• Among the principal challenges and key aspects of successful live cell imaging, optimization of microscopic settings, as well as, selection of culture environment and fluorescent components constitute the most remarkable ones.
• Providing a high quality imaging result, while maintaining an ideal environment for normal cellular behavior, and at the same time, avoiding occurrence of cellular cytotoxicity, is critical.
• The advent of new fluorescent nanoparticles and protein sensors confers this technology a broad spectrum of options to track cell dynamics. Coupled with high resolution microscopy approaches, in addition to micro technologies and nanotechnologies, live cell imaging reveals an untapped potential for healthcare industry.

Live, real-time processing
Although technically more challenging, live cell imaging constitutes the technology of choice for most researchers, as it enables studying cellular events and dynamic processes that cannot be visualized in fixed specimens. Live cell imaging helps life scientists to gain an in-depth understanding of and obtain new insights into the complex mechanisms of cell biology.

Specific, single cell analysis
The possibility to observe cellular phenomena at the level of single cells has significantly enriched the perspective from which biological processes are seen. Hence, in comparison with the conventional imaging techniques, which utilize averaged data from populations of cells, live cell imaging provides accurate and detailed results for every single cell.

Complex, dynamic response
With the emergence of live cell microscopy that allows visualizing individual cells, researchers are capable of achieving a broader landscape of the complex spatiotemporal kinetics of DNA responses, while also addressing the causes and consequences of heterogeneity in the responses of genetically identical cells.

Broad niche landscape
Live cell imaging has provided unprecedented knowledge related to cell response, such as, DNA double-strand breaks. Live cell imaging technologies find a large number of market niches in cell biology, cancer research, developmental biology, and neuroscience.

Cross-pollination disciplines
The integration of microfluidic systems and nanobiotechnology with microscopic imaging platforms enables life scientists to conduct more complex investigations, which may not be possible through more conventional techniques.

Drug discovery and development by
Predicting response to treatment, which can then guide clinical treatment.
Predict the likely outcome for a patient in terms of either disease or disease progression without treatment

Pre-clinical studies/clinical development by
Assessing the side effects caused by a drug.
Studying the effect of therapy

Diagnostics/screening by
Tagging changes related to disease onset or progression.
Evaluating the risk of development of a disease or for its detection at the early stages.

Clinical management by
Assessing therapeutics management based on a more personalized approach to medicine
Providing substantial support for surgical procedures
Addressing tumor resection, chemotherapy and physiotherapy programs

Life sciences research
Providing in-depth understanding of human cell biology
Supporting in vitro and in silico modeling and simulation
Generating computational biology input data

Light Microscopy
Light microscopy is the simplest and most widely used imaging technique that enables viewing of objects using visible wavelengths of light.
Electron microscope uses a beam of highly energetic electrons to examine objects on a very fine scale.
The scanning probe microscope forms images of surfaces using a physical probe that scans the specimen. Types of scanning probe microscopes include atomic force microscope, scanning tunneling microscope, and near-field scanning optical microscope.
surface examination

Fluorescence Resonance Energy Transfer (FRET)
Förster, commonly referred to as fluorescence resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET) events are used for detecting dynamic protein interactions in live-cell experiments. In particular, FRET assists in quantifying molecular dynamics, such as, protein-protein interactions, protein-DNA interactions, and protein conformational changes.
As fluorescent tags, FRET imaging normally uses green fluorescent protein (GFP) derivatives, attached to proteins of interest using molecular biology methods.
BRET uses a bioluminescent molecule, usually luciferase derivatives.
quantification protein-protein interactions

Fluorescence Recovery After Photo-bleaching (FRAP)
Fluorescence recovery after photobleaching (FRAP) is a method for monitoring protein and vesicle trafficking. The fluorescent protein (usually GFP) is attached to the protein of interest to monitor its dynamics.
Regions of the cell are exposed to high intensities of light, usually laser light, and the fluorescence in that particular region is destroyed through bleaching.
Intracellular transport dynamics can be monitored by observing proteins from other parts of the cell reinvade the bleached region at a certain speed, as well as, by the recovery of the fluorescence in the bleached region. This can give researchers insight into intracellular transport dynamics.
protein and vesicle trafficking monitoring

Total Internal Reflection Fluorescence (TIRF)
Total internal reflection fluorescence (TIRF) microscopy is a special technique for observing events that are located in or close to the plasma membrane of a cell.
TIRF microscopy provides unique information about plasma membrane events.
observation of cell membrane surroundings observation

Photoactivation
Photoactivation selectively labels certain areas of interest within a cell or a whole organism. Especially designed dyes or fluorescent proteins, such as photoactivatable green fluorescent protein (paGFP) or Kaede, are used. Being not fluorescent in their normal state, these fluorophores can be activated after illumination with light of certain wavelengths. These proteins can be genetically fused to certain proteins of interest, whose expression or transport need to be monitored.
monitoring gene expression and protein transportation

Multi-Photon Excitation (MPE)
Most biological research is performed in cell culture experiments, so that in vivo investigation is crucially needed to complement the information. Multi-photon excitation (MPE) microscopy allows researchers to penetrate deeper into tissues through near-infrared excitation light. Having a longer wavelength and less scattering compared to the short-wavelength light used for single-photon excitation, this non-linear technique restricts photobleaching and phototoxicity to the area in focus. This method has found wide application in neurobiology, and represents the selection of choice for long-term investigation.
understanding of cellular complexity

Table Of Contents

The Untapped Potential in Live Cell Imaging (Technical Insights)
Table of Contents

Executive Summary 3
Technology Snapshot and Trends 6
Technology Capabilities 7
Technology Value Chain 14
Impact Assessment and Analysis 16
Market Impact of Key Innovations 17
Market Impact of Business and Technological Challenges 18
Market Impact of Business and Technology Accelerators 19
Diffusion of Innovations and Needs Assessment 20
Technology Adoption Cycle 21
Demand Side Analysis 27
Opportunity Evaluation and Road Mapping 29
Potential Applications 30
• Core Innovations 32
• Core Growth Opportunities 36
Technology Roadmap 39
Contacts, Patents, and Decision Support Database Tables 41
The Frost and Sullivan Story 56

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