Diffusion-driven device for a high-resolution dose-response profiling of combination chemotherapy
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Diffusion-driven device for a high-resolution dose-response profiling of combination chemotherapy. / Ganser, Alexander; Roth, Günter; van Galen, Joost C; Hilderink, Janneke; Wammes, Joost J G; Müller, Ingo; van Leeuwen, Frank N; Wiesmüller, Karl-Heinz; Brock, Roland.
In: ANAL CHEM, Vol. 81, No. 13, 01.07.2009, p. 5233-40.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Diffusion-driven device for a high-resolution dose-response profiling of combination chemotherapy
AU - Ganser, Alexander
AU - Roth, Günter
AU - van Galen, Joost C
AU - Hilderink, Janneke
AU - Wammes, Joost J G
AU - Müller, Ingo
AU - van Leeuwen, Frank N
AU - Wiesmüller, Karl-Heinz
AU - Brock, Roland
PY - 2009/7/1
Y1 - 2009/7/1
N2 - Combination therapies have proven vital in the fight against HIV and cancer. However, the identification and optimization of such combination therapies is largely experience driven and an activity of clinicians rather than of systematic screening efforts. Here we present a diffusion device, compatible with the format of a 12-well microtiter plate, to create and test all possible mixtures of two substances with only two pipetting steps. Applications to the testing of different drug combinations and the parallel screening of different leukemia cell lines as well as primary patient cells are presented. The diffusion device yields qualitatively and quantitatively comparable results to an MTT viability assay conducted in a standard 96-well format albeit with a tremendous reduction of processing steps. In addition, a fluorescence-based annexin V binding assay of cell death was implemented. Next to the reduction of processing steps, the diffusion device constitutes a considerable assay miniaturization that overcomes the problems typically associated with miniaturization as a consequence of small sample volumes. Given its ease of handling, the device will greatly advance the development and optimization of combination drugs and the identification of optimum drug combinations in personalized medicine.
AB - Combination therapies have proven vital in the fight against HIV and cancer. However, the identification and optimization of such combination therapies is largely experience driven and an activity of clinicians rather than of systematic screening efforts. Here we present a diffusion device, compatible with the format of a 12-well microtiter plate, to create and test all possible mixtures of two substances with only two pipetting steps. Applications to the testing of different drug combinations and the parallel screening of different leukemia cell lines as well as primary patient cells are presented. The diffusion device yields qualitatively and quantitatively comparable results to an MTT viability assay conducted in a standard 96-well format albeit with a tremendous reduction of processing steps. In addition, a fluorescence-based annexin V binding assay of cell death was implemented. Next to the reduction of processing steps, the diffusion device constitutes a considerable assay miniaturization that overcomes the problems typically associated with miniaturization as a consequence of small sample volumes. Given its ease of handling, the device will greatly advance the development and optimization of combination drugs and the identification of optimum drug combinations in personalized medicine.
KW - Adenine Nucleotides
KW - Annexin A5
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Arabinonucleosides
KW - Cell Death
KW - Diffusion
KW - Dose-Response Relationship, Drug
KW - Doxorubicin
KW - Drug Therapy, Combination
KW - Fluorescent Dyes
KW - Humans
KW - Miniaturization
KW - Phosphatidylserines
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma
KW - Toxicity Tests
KW - Tumor Cells, Cultured
U2 - 10.1021/ac900415s
DO - 10.1021/ac900415s
M3 - SCORING: Journal article
C2 - 19476343
VL - 81
SP - 5233
EP - 5240
JO - ANAL CHEM
JF - ANAL CHEM
SN - 0003-2700
IS - 13
ER -