MultiPROBE nL Complements Drug Discovery Assay Miniaturization

1998 ◽  
Vol 3 (3) ◽  
pp. 237-239 ◽  
Author(s):  
Jennifer Driscoll ◽  
Ron Delmendo ◽  
Roeland Papen ◽  
David Sawutz
Keyword(s):  
Drug Discovery ◽  
Organic Solvents ◽  
Dose Response ◽  
Small Volume ◽  
Video Camera ◽  
Response Curves ◽  
Handling System ◽  
Liquid Handling ◽  
Dilution Step ◽  
Secondary Screening

The Packard MultiPROBE® nL is designed to enable the MultiPROBE Automated Liquid Handling System to aspirate and dispense nanoliter volumes. Several features add confidence to small volume transfers. A preview of nanoliter dispensing can be seen on a video camera monitor. In addition to the standard wash station, syringe and ultrasonic flushes can be run at the start of a program to prevent dirt or air obstructions. The MultiPROBE nL can transfer ionic, nonionic, and solutions containing organic solvents such as DMSO directly from master to assay plates and into high-density plate arrays. Additionally, the MultiPROBE nL increases the efficiency of generating dose response curves for secondary screening by eliminating a dilution step. IC50 values obtained after compound preparation with the instrument are consistent with those values previously determined using an MultiPROBE 208.

scholarly journals A 384-HTS for Human Factor VIIa: Comparison With 96- and 864-Well Formats

1997 ◽  
Vol 2 (3) ◽  
pp. 171-178 ◽  
Author(s):  
John C.W. Comley ◽  
Alastair Binnie ◽  
Caroline Bonk ◽  
John G. Houston
Keyword(s):  
Tissue Factor ◽  
Dose Response ◽  
Human Factor ◽  
Factor Viia ◽  
Assay Development ◽  
Fluorescent Detection ◽  
Response Curves ◽  
Liquid Handling ◽  
Dose Response Curves ◽  
Assay Volume

A homogenous fluorescent HTS for recombinant human factor VIIa (FVIIa) using soluble tissue factor has been developed in 384-well microplates. In this report we discuss our 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. Assays using the entire Helix 864-well plate were prototyped using contact dispensing with a modified Hamilton Microlab 2200. FVIIa was used as a model assay to compare between 96-, 384-, and 864-plate formats in a total assay volume of 100, 25, and 10 μl, respectively. FVIIa was assayed in 864 to the same degree of sensitivity as 384- and 96-well assays and dose-response curves for a standard inhibitor (benzamidine) in the FVIIa assay were identical in all plate formats. Finally, we review the prospects for HTS in 864-well microplates.

scholarly journals How Desirable Are Your IC50s?

2010 ◽  
Vol 15 (10) ◽  
pp. 1183-1193 ◽  
Author(s):  
Gaia V. Paolini ◽  
Richard A. Lyons ◽  
Philip Laflin
Keyword(s):  
Experimental Data ◽  
Biological Activity ◽  
Drug Discovery ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Response Curves ◽  
Dose Response Curves ◽  
Combine Information

Dose-response curves, resulting in estimates of endpoints such as the IC50, are fundamental to drug discovery. However, some estimates are more reliable than others. It is important to know just how reliable an estimate is if we want to base decisions on it or use it in further modeling. In this study, the authors propose a new measure of endpoint reliability, based on the concept of desirability first introduced by Harrington. The solution is not dependent on the application used to analyze the experimental data, provided a number of parameters to characterize the dose-response curve are available. The authors show how this score can be used as an objective and consistent measure to rank screening results, combine information from groups of experiments, and determine optimal levels of characterization of a compound’s biological activity.

Dose-response Curves in the Fibrin Plate Assay Fibrinolytic Activity of Proteases

1974 ◽  
Vol 32 (02/03) ◽  
pp. 356-365 ◽  
Author(s):  
F Haverkate ◽  
D. W Traas
Keyword(s):  
Dose Response ◽  
Fibrinolytic Activity ◽  
Enzyme Concentration ◽  
Response Curves ◽  
Agar Gel ◽  
Porcine Tissue ◽  
Plate Assay ◽  
Fibrin Plate ◽  
Different Types ◽  
Dose Response Curves

SummaryIn the fibrin plate assay different types of relationships between the dose of applied proteolytic enzyme and the response have been previously reported. This study was undertaken to determine whether a generally valid relationship might exist.Trypsin, chymotrypsin, papain, the plasminogen activator urokinase and all of the microbial proteases investigated, including brinase gave a linear relationship between the logarithm of the enzyme concentration and the diameter of the circular lysed zone. A similar linearity of dose-response curves has frequently been found by investigators who used enzyme plate assays with substrates different from fibrin incorporated in an agar gel. Consequently, it seems that this linearity of dose-response curves is generally valid for the fibrin plate assay as well as for other enzyme plate bioassays.Both human plasmin and porcine tissue activator of plasminogen showed deviations from linearity of semi-logarithmic dose-response curves in the fibrin plate assay.

Factor VII Clotting Assay: Influence of Different Thromboplastins and Factor VII-Deficient Plasmas

1991 ◽  
Vol 65 (02) ◽  
pp. 160-164 ◽  
Author(s):  
Marina Poggio ◽  
Armando Tripodi ◽  
Guglielmo Mariani ◽  
Pier Mannuccio Mannucci ◽  
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Dose Response ◽  
Response Curve ◽  
Ischemic Heart ◽  
Factor Vii ◽  
Response Curves ◽  
Assay Sensitivity ◽  
Clinical Laboratories ◽  
Coagulant Activity

SummaryBeing a putative predictor of ischemic heart disease, the measurement of factor VII (FVTI) coagulant activity will be presumably requested to clinical laboratories with increasing frequency. To assess the influence on FVII assays of different thromboplastins and FVII-deficient plasmas we compared performances of all possible combinations of 5 thromboplastins and 6 deficient plasmas. The reproducibility of the clotting times of the dose-response curves for human and rabbit thromboplastins were acceptable (CV lower than 7%), whereas bovine thromboplastin had a higher CV. Reproducibility was very similar for all deficient plasmas when they were used in combination with a given thromboplastin. Responsiveness of the dose-response curve did not depend on the deficient plasma but rather on the thromboplastin: one rabbit thromboplastin was the least responsive, the bovine thromboplastin the most responsive, the human and the remaining two rabbit thromboplastins had intermediate responsiveness. Assay sensitivity to cold-activated FVII varied according to the thromboplastin: the bovine thromboplastin was the most sensitive, the human thromboplastin the least sensitive, of the three rabbit thromboplastins two were relatively sensitive, one was almost insensitive. In conclusion, our results indicate that thromboplastin rather than deficient plasma is the crucial factor in the standardization of FVII assay.

OVARIAN ASCORBIC ACID DEPLETION TEST FOR LUTEINIZING HORMONE

1967 ◽  
Vol 56 (4) ◽  
pp. 619-625 ◽  
Author(s):  
Hans Jacob Koed ◽  
Christian Hamburger
Keyword(s):  
Ascorbic Acid ◽  
Luteinizing Hormone ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Human Origin ◽  
Response Curves ◽  
Significant Difference ◽  
The Mean ◽  
Different Levels

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.

BIOASSAY OF THYROID HORMONE USING HYPOTHYROID TADPOLES

1962 ◽  
Vol 41 (1) ◽  
pp. 143-153 ◽  
Author(s):  
U. Henriques
Keyword(s):  
Thyroid Hormone ◽  
Dose Response ◽  
Developmental Rate ◽  
Response Curves ◽  
Sodium Salts ◽  
Dose Response Curves

ABSTRACT A bioassay of thyroid hormone has been developed using Xenopus larvae made hypothyroid by the administration of thiourea. Only tadpoles of uniform developmental rate were used. Thiourea was given just before the metamorphotic climax in concentrations that produced neoteni in an early metamorphotic stage. During maintained thiourea neotoni, 1-thyroxine and 1-triiodothyronine were added as sodium salts to the water for three days and at the end of one week the stage of metamorphosis produced was determined. In this way identical dose-response curves were obtained for the two compounds. No qualitative differences between their effects were noted except that triiodothyronine seemed more toxic than thyroxine in equivalent doses. Triiodothyronine was found to be 7–12 times as active as thyroxine.

ÜBER DIE ANTAGONISTISCHE WIRKUNG VON TRIJODTHYRONIN UND PROGESTERON AUF DEN PREDNISOLONEFFEKT AM EPIPHYSENKNORPEL (PRÜFUNG DER REISSFESTIGKEIT)

1963 ◽  
Vol 42 (1) ◽  
pp. 29-38 ◽  
Author(s):  
L. Ther ◽  
H. Schramm ◽  
G. Vogel
Keyword(s):  
Tensile Strength ◽  
Dose Response ◽  
Single Injection ◽  
Relative Effectiveness ◽  
Prednisolone Acetate ◽  
Response Curves ◽  
Deoxycorticosterone Acetate ◽  
Weight Range ◽  
Diuretic Action ◽  
Maximal Load

ABSTRACT Longitudinal tension exerted on a killed rat's femur results always in rupture on the same place viz: the distal epiphyseal line. The power required to produce this effect can be measured with a simple dynamometer. The tensile strength increases with advancing age and during exsiccation (thirst). In untreated rats (weight range 100–120 g) this value amounts to about 1.5–1.8 kg. Tensile strength of the femoral epiphyseal line may be influenced by hormones. Corticosteroids such as prednisolone acetate and cortisol acetate increase the level of maximal load to more than 2.0 kg. In general the effect of a single injection reaches a climax after 48 hours. Dose-response-curves can be established and relative effectiveness may be gathered therefrom. Deoxycorticosterone acetate likewise increases tensile strength in spite of the fact that contrary to prednisolone exhibiting diuretic action this compound has a water retaining effect. Triiodothyronine and progesterone when given alone produce a slight decrease in tensile strength. The effect of prednisolone when given simultaneously with one of these two compounds is antagonized: this phenomenon is more pronounced in the case of triiodothyronine.

Dose Response Curves for Microwave Ablation in the Cardioplegia-Arrested Porcine Heart

2005 ◽  
Vol 8 (4) ◽  
pp. E269-E274 ◽  
Author(s):  
Sydney L. Gaynor ◽  
Gregory D. Byrd ◽  
Michael D. Diodato ◽  
Yosuke Ishii ◽  
Anson M. Lee ◽  
...  
Keyword(s):  
Dose Response ◽  
Microwave Ablation ◽  
Response Curves ◽  
Porcine Heart ◽  
Dose Response Curves

Modeling Nonmonotonic Dose-Response Curves

2001 ◽  
Author(s):  
Quinton J. Nottingham ◽  
Jeffrey B. Birch ◽  
Barry A. Bodt
Keyword(s):  
Dose Response ◽  
Response Curves ◽  
Dose Response Curves

scholarly journals Comment Concerning the Effects of Light Intensity on Melatonin Suppression in the Review “Light Modulation of Human Clocks, Wake, and Sleep” by A. Prayag et al.

2021 ◽  
Vol 3 (1) ◽  
pp. 181-188
Author(s):  
Peter Bracke ◽  
Eowyn Van de Putte ◽  
Wouter R. Ryckaert
Keyword(s):  
Phase Shift ◽  
Light Intensity ◽  
Dose Response ◽  
Light Modulation ◽  
Response Curves ◽  
Practical Applications ◽  
Circadian Phase ◽  
Melatonin Suppression ◽  
Dose Response Curves ◽  
Circadian Phase Shift

Dose-response curves for circadian phase shift and melatonin suppression in relation to white or monochromatic nighttime illumination can be scaled to melanopic weighed illumination for normally constricted pupils, which makes them easier to interpret and compare. This is helpful for a practical applications.

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