Biomedical Engineering Reference
In-Depth Information
The high impact of flow cytometry on clinical practice and research, together with
the availability of instrumentation, has fostered the view that flow cytometry is a
mature technology. This belies the continued appearance of advances in analysis
capacity, improvements in sorting, integration of sample handling solutions, and
enhanced event detection and resolution. Such developments carry burdens for
platform evaluation and cross-platform comparisons particularly when data from
trials depend onmulticenter analyses. For example, in the discrete area of hematology
analyzers, the introduction of new platforms (e.g., LH 750, Beckman Coulter;
Advia 120, Bayer Diagnostics; XE 2100, Sysmex; Excell 2280, Drew Scientific
Inc.) required cross-platform evaluations for analyte sample stability [1] or operation
within a given workload environment [2].
An emerging feature of the advance in the flowcytometry platform is the expansion
of multiparameter capacity and the provision of supporting reagent technologies as
addressed elsewhere in this topic. The success of the technology has also primed
awareness in microfluidics and the search for new modalities, beyond light scatter
and fluorescence, for both cell sensing and analysis. For the drug discovery sector,
innovation in cytometry presents issues for platform selection when coping with
biological/chemical diversity, the need for improved robotic handling, sample
throughput, and choice within an expanding range of screening applications that
require validation on a given platform [3]. This is a particular challenge when faced
with new and highly informative model systems, such as zebrafish (Danio rerio), for
discovery and drug development in the screening of lead compounds, target identi-
fication, target validation, and physiology-based assays including toxicity testing [4].
High-throughput multifactorial analysis has previously promised an enhanced effi-
ciency with which novel bioresponse-modifying drugs may be identified and
characterized [5]. Thus, in the drug discovery and development (DD&D) area, the
demand remains for higher throughput performance and “high-content” screening
applications [6, 7].
Multiparameter phenotypic profiling technologies for small molecules can im-
prove success rates of lead selection and optimization in the drug discovery path-
way [8]. In parallel, there is a recognition of the value of “cell-centric technologies”
particularly in oncology [9]. Recent advances in gene and small molecule delivery
modalities and automated systems for cell manipulation have supported such
approaches [9]. Flow cytometry stands alongside a range of specialized techniques
for performing cell-based assays in drug discovery and even has an expanding role
in profiling toxicology for ADME/Tox (absorption, distribution, metabolism, excre-
tion, and toxicology) evaluations. With its unique capacity to assess the dimensions
of heterogeneity in complex cellular systems, it continually finds new areas of
application.
Flow cytometry has a distinguished track record in providing elegant solutions in
the screening for antivirals, given the convenient cell surface presentation of key
target molecules. For example, hepatitis C virus (HCV) presents a significant health
challenge with an estimated 170 million individuals affected and is a challenge for
compound screening [10]. Attachment of the virus to the cell surface and viral entry
are critical for the initiation of infection, and an interaction between the envelope
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