89810-- Rapid Equilibrium Dialysis （RED） Device

Rapid Equilibrium Dialysis （RED） Device   

The Thermo Scientific Pierce RED Device for Rapid Equilibrium Dialysis was developed in close association with the pharmaceutical industry to provide the easiest, fastest and most reliable system for performing plasma protein-binding assays, which comprise a critical step in drug development.

• Easy and ready to use – disposable tubes require no presoaking, assembly or specialized equipment
• Designed for speed – the high surface-to-volume ratio of the insert design enables equilibrium to be reached in as few as 100 minutes with vigorous agitation or in three to four hours with 200rpm agitation
• Automation-compatible – designed on a standard 96-well plate template suitable for automated liquid handlers
• Flexible and scalable – perform any number of assays （1 to 48 assays per plate） without wasting the entire plate
• Robust – compartmentalized design eliminates potential for cross talk or leakage
• Reproducible and accurate – validated for plasma binding assays, producing results consistent with those reported in literature
• Quality-tested – each lot of inserts is functionally tested in a protein-binding assay for guaranteed performance

• Disposable: require no presoaking, assembly, or specialized equipment
• Short incubation time: large dialysis surface area accelerates equilibrium
• 8K MWCO membrane: ideal molecular-weight cutoff for protein-drug binding studies
• 12K or 25K MWCO membranes are also available as a custom order （minimum order, 10 plates） for larger drug molecules retained by the standard 8K MWCO
• Membrane composition: regenerated cellulose with low glycerol content as a humectant

• Microplate footprint: compatible with automated systems for 96-well plates
• Compartmentalized: eliminates potential for crosstalk or leakage
• PTFE construction: eliminates nonspecific binding and risk of contamination
• Accepts 1 to 48 inserts: run exactly the number of assays needed without waste

• Determination of free vs. drug bound to plasma proteins
• Pharmacokinetics studies
• Formulation of drug dosage for in vivo studies
• Drug-drug interaction studies
• Selection criteria during drug lead optimization
• Drug partition between plasma and whole blood
• Solubility study
• Dissociation constant determination （K_d）
• Tissue-binding study using tissue homogenate

Use the RED Device for increased productivity. Each RED Device Base Plate sits in a 96-well plate footprint withe 9 x 9 mm well spacing making it compatible with automated liquid handling systems. Single-Use RED Base Plates are available with inserts preloaded mimimizing setup time. Rapid Equilibrium Dialysis Device Frequently Asked Questions. Please click here to see the Rapid Equilibrium Device Demonstration Video.

The RED Device reproduces results found in the literature. Performance of pre-loaded Single-Use RED Device Base Plates （Product # 90006） using high, medium and low protein-binding compounds tested at 1 mM on human plasma.
	Human plasma （% bound）
Compound	RED plate	*Other Device
Warfarin	99.24	99
Taxol	96.16	95 to 98
Propanolol	91.81	80 to 92
Vinblastine	99.30	99
Verapamil	90.31	88 to 92
Atenolol	3.50	< 5
Antipyrine	0	0
*Values reported in the literature.2-6

The RED Device for comparison of plasma and microsome samples. Comparison of protein bindings between human plasma and human microsome at 1 mM concentration as determined using the Single-Use RED Device.
Compound	Human Plasma, % free	Human Microsome, % free
Warfarin	< 1	81
Taxol	4	20
Propanolol	8	44
Vinblastine	0.7	4
Verapamil	10	27
Methotrexate	50	70
Simvastatin	7	23
Atenolol	97	100
Antipyrine	100	100
*Microsomal protein concentration of 1.0 mg/ml is used in the study

The RED Device had many advantages to other methods. The RED Device System offers significant improvements in the ease of use, time requirements, versatility and product reliability compared to other methods.
Device	Time to reach Equilibrium	Disposable	Labor Intensity	Automation Accessible	Vol. Shift
RED （Rapid Equilibrium Dialysis）, （Pierce）	4 Hr	Yes	+	Yes	None
96 - well Micro Equilibrium Dialysis block （HTDDialysis, LLC）	6 Hr	No	+++	Possible	Yes
24-Multiwell Dialysis （BD Biosciences）	24 Hr	Yes	++	Possible	Not measured
Shelley Li1, Bob Xiong2, Tainang Huang2, Lily Li2, John Donovan3, Frank Lee*1, Shaoxia Yu1, Gerald Miwa1, Hua Yang*1 1DMPK/Drug Safety & Disposition, and 3Process Technology, Millennium Pharmaceuticals, Inc. 40 Landsdowne Street, Cambridge, MA 02139 USA and 2Linden Bioscience, 35A Cabot Road, Woburn, MA 01801, USA Equilibrium can be reached in as little as 100 minutes with mild agitation or 3-4 hours with no agitation.

Posters: Download a PDF version of the following posters.

1. Waters, N.J., et al. （2008）. Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding. J Pharm Sci 97（10）: 4586-95.
2. Brouwer, E.J., et al. （2000）. Measurement of fraction unbound paclitaxel in human plasma. Drug Metab Disposition 28（10）: 1141-5.
3. Brunton, L., et al. Goodman and Gilman's Pharmacological Basis of Therapeutics. McGraw Hill Publishing: New York, 2005.
4. Clausen, J. and Bickel, M. （1993）. Prediction of drug distribution in distribution dialysis and in vivo from binding to tissue and blood. J Pharm Sci 82: 345-9.
5. Sonnichsen, D. and Relling, M. （1994）. Clinical pharmacokinetics of paclitaxel. Clin Pharmacokinet 27: 256-69.
6. Steele, W., et al. （1983）. The protein binding of vinblastrine in the serum of normal subjects and patients with Hodgkin's disease. Eur J Clin Pharmacol 24: 683-7.

Ordering Information

Product # Description Pkg. Size Instructions MSDS CofA Price 90006 RED Device Single-Use Plate with Inserts, 8K MWCO Formulation: High-density polypropylene plate with RED Device Inserts Sufficient For: 1 × 48 experiments   1-plate set Local contact 90006B RED Device Single-Use Plate with lnserts, 8K MWCO Formulation: High-density polypropylene plate with RED Device Inserts Custom 90007 RED Device Single-Use Plate with Inserts, 8K MWCO Formulation: High-density polypropylene plate with RED Device Inserts Sufficient For: 5 × 48 experiments   5-plate set Local contact 99006 RED Device Single-Use Plate with Inserts, 8K MWCO Formulation: High-density polypropylene plate with RED Device Inserts Sufficient For: 10 × 48 experiments   10-plate set Local contact 89812 RED Device Insert Removal Tool Formulation: Stainless steel Sufficient For: Removing columns of RED Inserts from RED Base Plates （reusable）   1 tool Local contact 89809 RED Device Inserts, 8K MWCO Formulation: Plastic framed cellulose membrane tube Sufficient For: 50 equilibrium dialysis experiments with a RED Base Plate （sold separay）   50 inserts Local contact 89810 RED Device Inserts, 8K MWCO Formulation: Plastic framed cellulose membrane tube Sufficient For: 250 equilibrium dialysis experiments with a RED Base Plate （sold separay）   250 inserts Local contact 89811 RED Device Reusable Base Plate Formulation: High-grade PTFE Sufficient For: Unlimited （reusable） 48-well experiments with RED Inserts （sold separay）   1 plate Local contact 90004 RED Device Single-Use Base Plates Formulation: High-density polypropylene Sufficient For: 2 × 48 experiments （empty plates; require RED Inserts; sold separay）   2 plates Local contact 90005 RED Device Single-Use Base Plates Formulation: High-density polypropylene Sufficient For: 10 × 48 experiments （empty plates; require RED Inserts; sold separay）   10 plates Local contact