skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Design Considerations for High-throughput Screening (HTS) and In Vitro Diagnostic (IVD) Assays.


Abstract not provided.

Publication Date:
Research Org.:
Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
Report Number(s):
Journal ID: ISSN 1386-2073; 523034
DOE Contract Number:
Resource Type:
Journal Article
Resource Relation:
Journal Name: Combinatorial Chemistry & Highthroughput Screening; Journal Volume: 10; Journal Issue: 6; Related Information: Proposed for publication in Combinatorial Chemistry & Highthroughput Screening.
Country of Publication:
United States

Citation Formats

Achyuthan, Komandoor., and Whitten, David G. Design Considerations for High-throughput Screening (HTS) and In Vitro Diagnostic (IVD) Assays.. United States: N. p., 2007. Web. doi:10.2174/138620707781996475.
Achyuthan, Komandoor., & Whitten, David G. Design Considerations for High-throughput Screening (HTS) and In Vitro Diagnostic (IVD) Assays.. United States. doi:10.2174/138620707781996475.
Achyuthan, Komandoor., and Whitten, David G. Tue . "Design Considerations for High-throughput Screening (HTS) and In Vitro Diagnostic (IVD) Assays.". United States. doi:10.2174/138620707781996475.
title = {Design Considerations for High-throughput Screening (HTS) and In Vitro Diagnostic (IVD) Assays.},
author = {Achyuthan, Komandoor. and Whitten, David G.},
abstractNote = {Abstract not provided.},
doi = {10.2174/138620707781996475},
journal = {Combinatorial Chemistry & Highthroughput Screening},
number = 6,
volume = 10,
place = {United States},
year = {Tue May 01 00:00:00 EDT 2007},
month = {Tue May 01 00:00:00 EDT 2007}
  • We present a risk-based high-throughput screening (HTS) method to identify chemicals for potential health concerns or for which additional information is needed. The method is applied to 180 organic chemicals as a case study. We first obtain information on how the chemical is used and identify relevant use scenarios (e.g., dermal application, indoor emissions). For each chemical and use scenario, exposure models are then used to calculate a chemical intake fraction, or a product intake fraction, accounting for chemical properties and the exposed population. We then combine these intake fractions with use scenario-specific estimates of chemical quantity to calculate dailymore » intake rates (iR; mg/kg/day). These intake rates are compared to oral equivalent doses (OED; mg/kg/day), calculated from a suite of ToxCast in vitro bioactivity assays using in vitro-to-in vivo extrapolation and reverse dosimetry. Bioactivity quotients (BQs) are calculated as iR/OED to obtain estimates of potential impact associated with each relevant use scenario. Of the 180 chemicals considered, 38 had maximum iRs exceeding minimum OEDs (i.e., BQs > 1). For most of these compounds, exposures are associated with direct intake, food/oral contact, or dermal exposure. The method provides high-throughput estimates of exposure and important input for decision makers to identify chemicals of concern for further evaluation with additional information or more refined models.« less
  • A high-throughput protein-expression and screening method (HIGH method, see picture) provides a rapid approach to the discovery of active glycoside hydrolases in environmental samples. Finally, HIGH screening combines cloning, protein expression, and enzyme hydrolysis in one pot; thus, the entire process from gene expression to activity detection requires only three hours.
  • This paper presents a computational approach to the deliberate design of improved host architectures. The approach, which involves the use of computer-aided design software, is illustrated by application to cation hosts containing multiple aliphatic ether oxygen binding sites. De novo molecule building software, HostDesigner, is interfaced with molecular mechanics software, GMMX, providing a tool for generating and screening millions of potential bidentate building block structures. Enhanced cation binding affinity can be achieved when highly organized building blocks are used to construct macrocyclic hosts.
  • The design, synthesis and utility of fluorescence probes that bind to the DFG-out conformation of p38{alpha} kinase are described. Probes that demonstrate good affinity for p38{alpha}, have been identified and one of the probes, PF-04438255, has been successfully used in an high throughput screening (HTS) assay to identify two novel non-classical p38{alpha} inhibitors. In addition, a cascade activity assay was utilized to validate the selective binding of these non-classical kinase inhibitors to the unactive form of the enzyme.