The chemical-biological interface: developments in automated and miniaturised screening technology
Current Opinion in BiotechnologyPublished 1 December 1997
John G. Houston, Martyn Banks
Citations83
SJR quartileQ1
SJR score1.86
SNIP1.50
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The rapidly changing developments in genomics and combinatorial chemistry, generating new drug targets and large numbers of compounds, have caused a revolution in high-throughput screening technologies, with the introduction of robotics and automation together with new biological assay technologies.
Abstract
The rapidly changing developments in genomics and combinatorial chemistry, generating new drug targets and large numbers of compounds, have caused a revolution in high-throughput screening technologies. Key to this revolution has been the introduction of robotics and automation, together with new biological assay technologies (e.g., homogeneous time resolved fluorescence). With ever increasing workloads, together with economic and logistical constraints, miniaturisation is rapidly becoming essential for the future of high-throughput screening and combinatorial chemistry. This is evident from the introduction of high-density microtitre plates, small volume liquid handling robots and associated detection technology.
Keywords
Biochemistry, Genetics and Molecular BiologyEngineering
ScienceFilamentous Fusion Phage: Novel Expression Vectors That Display Cloned Antigens on the Virion Surface
4,097 Citations1985George P. Smith
Foreign DNA fragments can be inserted into filamentous phage gene III to create a fusion protein with the foreign sequence in the middle that is incorporated into the virion, which retains infectivity and displays the foreign amino acids in immunologically accessible form.
Proceedings of the National Academy of SciencesGeneral method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids.
1,651 Citations1985Richard A. Houghten
Through examination of the binding of these analogs to monoclonal antibodies raised against residues 75-110 of HA1, it was found that a single amino acid, aspartic acid at position 101, is of unique importance to the interaction.
Proceedings of the National Academy of SciencesUse of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid.
1,479 Citations1984H. Mario Geysen, Rob H. Meloen +1 more
It was found that the leucine residues at positions 148 and 151 were essential for reaction with antisera raised against intact virus, and may lead to better understanding of the basis of antigen-antibody interaction and antibody specificity.
NatureGeneration and use of synthetic peptide combinatorial libraries for basic research and drug discovery
1,330 Citations1991Richard A. Houghten, Clemencia Pinilla +4 more
The precise identification of an antigenic determinant recognized by a monoclonal antibody as well as the straightforward development of new potent antimicrobial peptides are presented.
Journal of Medicinal ChemistryApplications of Combinatorial Technologies to Drug Discovery. 2. Combinatorial Organic Synthesis, Library Screening Strategies, and Future Directions
1,145 Citations1994Eric M. Gordon, Ronald W. Barrett +3 more
NatureA biosensor that uses ion-channel switches
1,116 Citations1997Bruce Cornell, V. L. B. Braach‐Maksvytis +5 more
A biosensing technique in which the conductance of a population of molecular ion channels is switched by the recognition event, which mimics biological sensory functions and can be used with most types of receptor, including antibodies and nucleotides.
Proceedings of the National Academy of SciencesPeptides on phage: a vast library of peptides for identifying ligands.
930 Citations1990Steven E. Cwirla, Elizabeth A. Peters +2 more
A vast library of peptides is constructed for finding compounds that bind to antibodies and other receptors and shows that ligands can be identified with no prior information concerning antibody specificity.
Proceedings of the National Academy of SciencesGeneration and screening of an oligonucleotide-encoded synthetic peptide library.
347 Citations1993Michael C. Needels, David G. Jones +6 more
By combining the capacity for information storage in an oligonucleotide code with the tremendous level of amplification possible through the PCR, this work has devised a means for specifying the identity of each member of a vast library of molecules synthesized from both natural and unnatural chemical building blocks.
NatureEducation reforms struggle against apartheid's legacy
292 Citations1996James R. Broach, Jeremy Thorner
The adoption of high-throughput screening as a primary tool for early-stage drug discovery has stimulated the adoption of new approaches that have increased the number of compounds that can be tested for activity against these targets.
Clinical & Translational OncologyHigh throughput screening in drug discovery
280 Citations2006Amancio Carnero
New developments in large-scale cell biology and compound library design in silico have evolved to obtain data with higher predictability of clinical efficacy, which would help reduce the cost and time of drug discovery.
Analytical ChemistryCharacterization of an Inkjet Chemical Microdispenser for Combinatorial Library Synthesis
150 Citations1997Anthony V. Lemmo, Jeffrey T. Fisher +2 more
Drug Discovery TodayTime-resolved fluorometry: an overview of the labels and core technologies for drug screening applications
150 Citations1997Ilkka Hemmilä, Stuart Webb
The ability of TRF technology to combine temporal resolution with high spatial resolution opens up the possibility of assay configurations with features such as miniaturization, multilabel or multiparametric analysis and greatly improved sample throughput.
Medical Entomology and ZoologyHigh Throughput Screening: The Discovery of Bioactive Substances
107 Citations1997John P. Devlin
Sensors and Actuators A PhysicalUltimate limits in the miniaturization of chemical sensors
80 Citations1996Wolfgang Göpel
Journal of Chemical Information and Computer SciencesCombinatorial Chemistry and Molecular Diversity. An Overview
75 Citations1997Wendy A. Warr
The principles of design and synthesis of small molecule libraries and software being developed in generation of molecular diversity, in molecular design and analysis, in handling the information explosion, in information management, and in decision support to enable drug discovery groups to accelerate the planning and development of libraries.
Analytical BiochemistryA High-Density Screening Format for Encoded Combinatorial Libraries: Assay Miniaturization and Its Application to Enzymatic Reactions
61 Citations1997John R. Schullek, John H. Butler +3 more
The structure-activity relationship data generated from the identified inhibitors in this study corroborate previous findings, thus validating the utility of this approach as a means of high-throughput screening of bead-based libraries.
SLAS DISCOVERYUse of a Novel Homogeneous Fluorescent Technology in High Throughput Screening
57 Citations1996Janet M. Kolb, Gregory Yamanaka +1 more
This HTRF technique is robust and sensitive, and its utility in a high throughput screening format is reported here.
Drug Discovery TodayExperimental design for high-throughput screening
53 Citations1996Michael W. Lutz, J. Alan Menius +5 more
The use of statistical experimental design in the development and optimization of high-throughput screening assays and the power of the method in solving problems in assay development is demonstrated.
PubMedDirected combinatorial chemistry.
52 Citations1996Hogan Jc
It has become possible to use solid- or solution-phase syntheses with different chemistries and scaffolds to produce libraries tailor-made for finding or optimizing a lead directed at almost any class of target.
SLAS DISCOVERYFluorescence Polarization Assays for the Detection of Proteases and Their Inhibitors
48 Citations1996Michael E. Jolley
The development of highly sensitive, pH-independent assays using BODIPY(r)*-labeled a-caseins at fluorescein and Texas Red wavelengths are described, which readily lend themselves to the high throughput screening of compound libraries for protease inhibitors.
Journal of Receptors and Signal TransductionMinireview: Fluorescence Correlation Spectroscopy (FCS) - A Highly Sensitive Method to Analyze Drug/Target Interactions
46 Citations1997Sylvia Sterrer, Karsten Henco
FCS is fully compatible with standard microtiter plate formats, however, for high throughput screening, specially designed sample carriers containing many thousand sub-microliter sample wells may be used in combination with a nanopipetting and sample retrieval system.
Drug Discovery TodayPharmaceutical innovation between scientific opportunities and economic constraints
30 Citations1997Jürgen Drews, Stefan Ryser
This study tries to quantify the problem of shrinking repertoire of diseases seriously addressed by large pharmaceutical companies and to identify mechanisms through which the apparent conflict may be resolved.
Drug Discovery TodayStrategic choices facing the pharmaceutical industry: A case for innovation
30 Citations1997Jürgen Drews
The author discusses the different approaches to innovation that are available to the leading pharmaceutical companies and argues for the ‘offensive’ strategy.
Molecular DiversityDesign, synthesis and use of binary encoded synthetic chemical libraries
27 Citations1996John J. Baldwin
This split-and-pool approach, employing chemically robust tags, was used to construct a 85 000-membered dihydrobenzopyran library, and was the most powerful of the solid-phase methods.
Nature BiotechnologyAffinity—based screening of combinatorial libraries using automated, serial-column chromatography
23 Citations1996David M. Evans, Kevin P. Williams +5 more
An automated serial chromatographic technique for screening a library of compounds based upon their relative affinity for a target molecule and demonstrated the applicability of the technology towards selection of peptides with predetermined affinity for bacterial lipopolysaccharide (LPS, endotoxin).
SLAS DISCOVERYBeyond the 96-Well Microplate: Instruments and Assay Methods for the 384-Well Format
22 Citations1997Alfred J. Kolb, Kenneth Neumann
Reagent pipetting for SPA, including the scintillating beads, was performed with the MultiPROBETm 104 Automated Liquid Handling System, which has both the positioning and pipetting accuracy to support the 384-well microplate; therefore, making complete automation practical.
Analytical BiochemistryA Cell-Free, Nonisotopic, High-Throughput Assay for Inhibitors of Type-I Interleukin-1 Receptor
17 Citations1996Edoardo Sarubbi, Stephen Yanofsky +2 more
The microplate format and colorimetric detection have allowed the complete automation of the immobilized-ligand IL-1 receptor binding assay, which has been used for high-throughput screening of synthetic compounds and natural products.
SLAS DISCOVERYTransducer-Based Approaches for Parallel Binding Assays in HTS
17 Citations1996Andreas Brecht, Ralph Burckardt +7 more
First results from transducer-based approaches in drug screening using microelectrodes for competitive binding assay with a redox-labeled reference compound and the potential for further improvement of performances is discussed.
Laboratory Robotics and AutomationHigh throughput screening as a discovery tool in the pharmaceutical industry
17 Citations1996William P. Janzen
The popularity of high throughput screening in discovery programs has continued to rise in recent years, and the application of rigorous process controls to biological assays in conjunction with advances in automation and data handling have increased the testing rates and accuracies to the point where major pharmaceutical companies cannot afford to be without HTS programs.
Drug Discovery TodayDevelopment of an automated high-throughput screening system: a case history
16 Citations1997D. R. Harding, Martyn Banks +2 more
The automation of high-throughput screening (HTS) is progressing rapidly in the drug discovery world, and this report describes how one such automated HTS facility was developed, with emphasis on the flexibility of the final system.
SLAS DISCOVERYA 384-HTS for Human Factor VIIa: Comparison With 96- and 864-Well Formats
16 Citations1997John C.W. Comley, A. J. Binnie +2 more
The experiences with assay development, liquid handling using a Tomtec Quadra and Matrix PlateMate, fluorescent detection and screening of -200,000 compounds against FVIIa in 384-well plate format, and the prospects for HTS in 864-well microplates are discussed.
Analytical BiochemistryDevelopment of a High Volume Screen to Identify Inhibitors of Endothelial Cell Activation
15 Citations1996John W. Rice, Jefferson E. Davis +2 more
A screening paradigm was described which allowed us to identify inhibitors of endothelial cell activation and simultaneously discriminate their activity from their cytotoxic effects, and provide early information on the cellular uptake and cytotoxicity of compounds.
SLAS DISCOVERYA New Analytical Device Based on Gated Ion Channels: A Peptide-Channel Biosensor
13 Citations1997Ch. Weiss-Wichert, Michaela M. Smetazko +2 more
The new type of biosensor combines sensor design and technology from immunoassays and biorecognition assays with automated analysis systems and knowledge from the field of nanotechnology.
Clinics in Laboratory MedicineThe Advance of Technology As A Prelude to the Laboratory of the Twenty-First Century
12 Citations1994Jannie Woo, John B. Henry
Bedside testing using biosensor technology appears to offer unique opportunities for earlier availability of clinical laboratory data, decision making, and more specific diagnosis, and faster and more frequent monitoring; these may translate into improved patient care and reduced hospital costs.
SLAS DISCOVERYSearching for Chemokine Receptor Binding Antagonists by High Throughput Screening
11 Citations1997Geoffrey W. Mellor, Simon W. Fogarty +6 more
The process as applied to the discovery of selective antagonists of three chemokine receptor binding systems, from the original biological targets to chemically prosecutable lead compounds, which are currently being investigated using traditional medicinal and combinatorial chemistry methods are described.
Bioorganic & Medicinal ChemistryLead development: Validation and application of high throughput screening for determination of pharmacokinetic parameters for enzyme inhibitors
9 Citations1996Jasbir Singh, Jim Soloweij +3 more
An approach utilizing robotics (automation) for the rapid and reliable determination of protease inhibitor concentration in rat plasma samples is described, and the bioassay protocol using an immobilized peptide substrate allows high sample throughput, compatible with parallel synthesis/SAR development strategy.
SLAS DISCOVERYTransforming Your Robotics Into an Infrastructure for the Future
9 Citations1997John Babiak
The four infrastructural elements for effective high throughput screening are Sample Sourcing, Screen Design, Robotic Hardware, and Data Management, which must all work together to achieve a balance between flexibility and productivity.
Laboratory Robotics and AutomationApproaches to automation for high-throughput screening
6 Citations1996Melvin Reichman, Edward Marples +1 more
Specific examples of emerging robotic systems that are capable of ultrahigh-throughput screening capacities and utilize novel design principles will be discussed, and these ubotic HTS approaches will be described.
SLAS DISCOVERYUtilization of the ORCA to Completely Automate Scintillation Proximity Assays
4 Citations1996Catherine McCaffrey, Gordon Powers +1 more
Control data was compiled to assess the quality of results generated by a completely automated HTS system, and consistency and reproducibility of the data led to the elimination of duplicate determinations and doubling throughput to 2000 compounds/8 h.
Journal of Analytical Methods in ChemistryTeam building and leadership in thesuccessful implementation of automationfor high throughput screening
3 Citations1996Derek J. Hook
Why high throughput screening programmes have become a fast growing area in which laboratory automation is playing a critical role and how a team-based approach has become crucial in the successful implementation of these tasks is explained.
Laboratory Robotics and AutomationAutomated high throughput RT-PCR
2 Citations1996Jason W. Armstrong, Mike Tipsword +3 more
The automation pathway taken to provide high throughput screening of mRNA from human, mouse, and rat species is described.
ChemInformChemInform Abstract: Automating Combinatorial Chemistry: Challenges and Pitfalls
1 Citations1998Jill H. Hardin, Frank R. Smietana