TY - JOUR
T1 - Streamlining the Drug Discovery Process by Integrating Miniaturization, High Throughput Screening, High Content Screening, and Automation on the CellChip™ System
AU - Kapur, Ravi
AU - Giuliano, Kenneth A.
AU - Campana, Martha
AU - Adams, Terri
AU - Olson, Keith
AU - Jung, David
AU - Mrksich, Milan
AU - Vasudevan, Chandrasekaran
AU - Taylor, D. Lansing
N1 - Funding Information:
The authors acknowledge the contributions of Robbin DeBiasio, Joanne Volosky, LongGuang Cao, and Jefferson Paslay to the CellChipTM program. This work is supported in part by the DoD under a DARPA contract (N00014-98-C-0326), and a Program Project Grant from NCl (P01 CA78039-01).
PY - 1999
Y1 - 1999
N2 - A major bottleneck to the early stages of drug discovery is the absence of integration of high throughput screening (HTS) with smarter assays that screen "hits" from HTS to identify leads (High content screening, HCS). We propose a solution using novel fluorescent engineered protein biosensors integrated into a miniaturized live-cell-based screening platform (CellChip™ System) that markedly shortens the early drug discovery process. Microarrays of selectively localized living cells, containing engineered fluorescent biosensors, serve to integrate HTS and HCS onto a single platform. HTS "hits" are identified using one biosensor while reading the whole chip array of cells. The high-biological content information is then obtained from probing target activity at inter-cellular, sub-cellular and molecular levels in the "hit" wells. HCS assays yield temporal-spatial dynamic maps of the drug-target interaction within each living cell. We predict that a new platform incorporating HTS and HCS assays that are automated, miniaturized, and information-rich will dramatically improve the decision making process in the pharmaceutical industry and optimize lead compounds during the early part of the drug discovery process. There is an opportunity to establish a new paradigm for drug discovery based on integration of fluorescence technology, micropatterning of living cells, automated optical detection and data analysis, and a new generation of knowledge building bioinformatics approaches. The technology will have an expansive impact spanning the fields of drug discovery, biomedical research, environmental monitoring, life sciences, and clinical diagnostics. The integrated CellChip™ Platform with miniaturized tissue-specific microarrayed cells capable of providing inter-cellular and sub-cellular spatio-temporal information in response to drug-cell, toxin-cell, or pathogen-cell interactions will serve to enhance the decision making process in drug discovery, toxicology, and clinical diagnostics.
AB - A major bottleneck to the early stages of drug discovery is the absence of integration of high throughput screening (HTS) with smarter assays that screen "hits" from HTS to identify leads (High content screening, HCS). We propose a solution using novel fluorescent engineered protein biosensors integrated into a miniaturized live-cell-based screening platform (CellChip™ System) that markedly shortens the early drug discovery process. Microarrays of selectively localized living cells, containing engineered fluorescent biosensors, serve to integrate HTS and HCS onto a single platform. HTS "hits" are identified using one biosensor while reading the whole chip array of cells. The high-biological content information is then obtained from probing target activity at inter-cellular, sub-cellular and molecular levels in the "hit" wells. HCS assays yield temporal-spatial dynamic maps of the drug-target interaction within each living cell. We predict that a new platform incorporating HTS and HCS assays that are automated, miniaturized, and information-rich will dramatically improve the decision making process in the pharmaceutical industry and optimize lead compounds during the early part of the drug discovery process. There is an opportunity to establish a new paradigm for drug discovery based on integration of fluorescence technology, micropatterning of living cells, automated optical detection and data analysis, and a new generation of knowledge building bioinformatics approaches. The technology will have an expansive impact spanning the fields of drug discovery, biomedical research, environmental monitoring, life sciences, and clinical diagnostics. The integrated CellChip™ Platform with miniaturized tissue-specific microarrayed cells capable of providing inter-cellular and sub-cellular spatio-temporal information in response to drug-cell, toxin-cell, or pathogen-cell interactions will serve to enhance the decision making process in drug discovery, toxicology, and clinical diagnostics.
KW - Bioinformatics
KW - CellChip
KW - Drug discovery
KW - Fluorescence
KW - High content screening
KW - Microarrays
KW - Patterning
KW - Sensors
KW - Tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=0001956036&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0001956036&partnerID=8YFLogxK
U2 - 10.1023/A:1009993519771
DO - 10.1023/A:1009993519771
M3 - Article
AN - SCOPUS:0001956036
VL - 2
SP - 99
EP - 109
JO - Biomedical Microdevices
JF - Biomedical Microdevices
SN - 1387-2176
IS - 2
ER -