Journal of Pharmacological
`
`and Toxicological Methods 612010 329333
`
`Contents lists available at ScienceDirect
`
`Tasuolosita9 Methods
`
`Journal of Pharmacological and Toxicological Methods
`
`journal homepage wwwelseviercomlocatejpharmtox
`
`SEWER
`
`Original article
`
`Reduction of nonspecific adsorption of drugs to plastic containers used in
`bioassays or analyses
`
`Tominaga Fukazawa
`
`Yuri Yamazaki Yohei Miyamoto
`
`Toxicology
`
`and Pharmacokinetics Laboratories Pharmaceutical Research Laboratories Toray Industries Inc 6101 Tebiro Kamakura Kanagawa
`
`2488555 Japan
`
`ARTICLE INFO
`
`ABSTRACT
`
`Article history
`
`Received
`21 December 2009
`Accepted 21 December 2009
`
`Keywords
`
`3Glycidoxypropyltrimethoxysilane
`
`Nonspecific
`
`adsorption
`
`Silane coupling agent
`
`1 Introduction
`
`Introduction Non specific adsorption NSA of drugs to plastic or glass containers used in clinical use is
`reducing NSA have been rarely reported We assessed the NSA to various
`well known but methods for
`containers and then investigated methods to reduce NSA Methods Probe drugs methotrexate warfarin
`propranolol verapamil digoxin and paclitaxel dissolved in water were incubated in
`chloroquine
`conventional or low adsorption containers for 4 h at 4 °C and the NSA was determined by HPLC They
`were also dissolved in aqueous methanol or acetonitrile and the NSA to a conventional polypropylene
`microplate was determined Finally tissue culture microplates were coated with silane coupling agents and
`the effects of the coatings were evaluated Results Hydrophobic drugs paclitaxel verapamil and digoxin
`were highly adsorbed to conventional plastic microplates but
`in addition to hydrophobic drugs positively
`charged drugs were well adsorbed to the tissue culture microplate Low adsorption microplates could reduce
`NSA below 15 but positively charged or neutral hydrophobic drugs showed relatively higher adsorption
`Acetonitrile showed stronger NSA inhibition than that of methanol but the peak shapes of methotrexate and
`chloroquine were broadened and split Among the silane coupling agents GPTMS suppressed
`the NSA below
`10 Also AATMS resembled the NSA pattern of GPTMS but it
`increased
`the adsorption of methotrexate to
`29 Discussion On conventional plastic microplates NSA is mainly driven by hydrophobic interactions but
`on tissue culture microplates and low adsorption microplates
`in addition to hydrophobic interactions ionic
`interactions play a role in the NSA Therefore to reduce the NSA to plastic containers both hydrophobic and
`ionic interactions should be reduced using amphiphilic organic solvents or neutral and hydrophilic coatings
`0 2010 Elsevier Inc All rights reserved
`
`adsorption NSA of drugs to plastic or glass
`Non specific
`used in clinical use is well known and it decreased the
`containers
`of drugs critically in some cases Geary Akood 82
`concentration
`Jensen 1983 Yahya McElnay 82 DArcy 1988
`In bioassays eg plasma protein binding Caco
`experiment etc or analytical conditions the concentrations
`of drugs
`are much lower than in clinical use and therefore the effects of NSA
`to be more potent
`than
`on the assays or analyses are considered
`clinical use Robert 2006 For example 90 or more loss of drug
`resulted from NSA to ultrafiltration
`concentration
`and
`devices
`underestimation of drug concentrations
`during Caco 2 cell transport
`experiments due to NSA were reported Joni Jukka Timo Anssi
`Seppo 2006 Nanying et al 2002
`
`2 cell
`
`transport
`
`82
`
`Corresponding author Tel +81 467 32 2111 fax +81 467 32 9768
`Email address TominagaFukazawantstoraycojp T Fukazawa
`
`10568719$
`
`see front matter 0 2010 Elsevier Inc All
`
`rights reserved
`
`doi101016jvascn200912005
`
`that originate in
`
`NSA is
`largely the result of binding forces
`electromagnetic interactions and in this case it
`is roughly divided
`into ionic adsorption and hydrophobic adsorption Di Li
`fen
`Jessie
`1995 Joni et al 2006 Ionic adsorption is an interaction of a
`hydrophilic group on a surface eg silanol on glass and ionic groups
`of drugs eg chloroquine
`and hydrophobic adsorption van der
`Waals adsorption is an interaction of a hydrophobic surface eg
`plastic and hydrophobic drugs eg paclitaxel digoxin verapamil
`recently became more hydrophobic and
`Because drug candidates
`less soluble Christopher 2000 and the containers
`used in assays
`have also started to be made from hydrophobic plastics hydrophobic
`adsorption is mainly responsible for NSA Pradip 1998 To overcome
`the NSA to plastic plates commercially available
`low adsorption
`microplates often introduced hydrophilic groups on the surface of the
`82 Heinrich 2008
`microplates Rainer Claudia Ramona Gunther
`These modifications reduced the hydrophobic adsorption of highly
`hydrophobic drugs such as paclitaxel or digoxin Stan et al 2004 but
`the effect on the adsorption of drugs suspected of ionic adsorption
`remained unclear
`Any method to reduce or eliminate the NSA of drugs which have a
`wide variety of hydrophobicity
`and ionization tendencies may be
`useful Therefore we investigated a method to reduce the overall NSA
`
`Abraxis EX2036
`Actavis LLC v Abraxis Bioscience LLC
`1PR201701101 1PR201701103 1PR201701104
`
`

`

`330
`
`T Fukwawa et at
`
`Journal of Pharmacological and Toxicological
`
`Methods 612010 329333
`
`used in assays or analytical experiments The target
`to containers
`value of NSA was set to 10 taking into account
`the FDAs guidance
`that allows the maximum deviation on the analysis to be 15 US
`Department of Health and Human Services Food and Drug Admin
`istration 2001
`
`26 Data analysis
`
`The adsorption rate S was calculated using the following equation
`
`S = 1A A0 x 100
`
`2 Methods
`
`21 Chemicals
`
`Digoxin methotrexate propranolol and ± verapamil hydrochlo
`from Sigma Aldrich St Louis MO USA
`ride were purchased
`Chloroquine diphosphate paclitaxel and warfarin were obtained from
`Wako Pure Chemical
`Industries Osaka Japan Tetraethyl orthosilicate
`from Sigma Aldrich St Louis MO USA
`TEOS was purchased
`Vinyltrimethoxysilane VTMS 3 glycidoxypropyltrimethoxysilane
`GPTMS and N 2 aminoethyl 3 aminopropyltrimethoxysilane
`AATMS were obtained from Shin Etsu Chemical Tokyo Japan
`
`22 Containers
`
`Glass vials and Plate+ were purchased from Tomsic Tokyo Japan
`Conventional
`non treated polypropylene microplates
`polystyrene
`microplates and NoBinding
`plates were obtained from Greiner Japan
`Tokyo Japan MultichemTM microplates Proteosave
`96F plates
`plates and tissue culture treated polystyrene
`Enhanced Recovery
`by GE Healthcare Japan Tokyo Japan
`microplates were provided
`Sumitomo Bakelite Tokyojapan Becton Dickinson Franklin Lakes NJ
`USA and Asahi Glass Tokyo Japan respectively
`
`23 Silane coupling agent
`
`treatment to microplates
`
`To 495 mL of 1 acetic acid 05 mL of a silane coupling
`TEOS VFMS GPTMS or AATMS was added and stirred for
`1 h at
`room temperature The hydrolyzed coating agent was added to wells
`tissue culture treated polystyrene microplate and allowed to
`of a
`stand for 1 min at room temperature After disposal of surplus coating
`the microplate was dried and condensed at 50 °C for 4 h
`
`agent
`
`agent
`
`24 Evaluation of NSA
`
`Each drug was dissolved
`in dimethyl sulfoxide at a concentration
`of 10 mmolL To 998 IL of solvent distilled water aqueous methanol
`or aqueous acetonitrile 2 AL of a probe drug solution was added and
`stirred This solution was chilled at 4°C for 30 min diluted 10 times by
`chilled medium 4°C in the test container and analyzed sequentially
`for 4 h using HPLC
`
`where A0 is the initial peak area and A is the peak area of tin h
`
`3 Results
`
`31 NSA to conventional plastic and glass containers
`
`The probe drugs shown in Table l were selected according to their
`solubility to water charge in water and adsorption rate to plastic or
`glass Bergstrom 2003 Brigitte et al 2000 Elizabeth Kulpinski
`2006 Geary
`et al 1983 Hiroki Kohji Noriyoshi Katsuhiko
`Nobuyoshi 2006 Nanying et al 2002 Yalkowsky
`Dannenfelser
`Rubessa 2005
`1992 Zingone
`To initiate the study the NSAs of the probe drugs to conventional
`non treated
`plastic and glass containers were measured Fig 1
`shows the time course of the adsorption rate of the probe drugs to a
`conventional
`polystyrene microplate The adsorption rates of digoxin
`verapamil and paclitaxel exceeded 10 and the adsorption rate of
`paclitaxel was the highest among the probe drugs In this experiment
`the adsorption rates of each drug were nearly identical from 2 to 4 h
`after incubation
`The mean adsorption rates from 2 to 4 h after incubation in the
`conventional
`polystyrene microplate polypropylene microplate and
`glass vial are shown in Fig 2 To the conventional
`plastic microplates
`the adsorption rates of paclitaxel were the highest and reached 65
`67 while verapamil and digoxin also adsorbed over 20 22 42 In
`addition to these drugs propranolol was adsorbed at over 10 to the
`polypropylene microplate To the glass vial chloroquine showed the
`highest adsorption rate 42 and the adsorption rate of verapamil
`was also over 10
`
`32 NSA to low adsorption microplates
`
`The mean adsorption rates of the probe drugs to low adsorption
`microplates are summarized in Fig 3 To a Multichem microplate the
`adsorption rate of paclitaxel was the highest 61 and the adsorption
`rate of digoxin was over 10 To a Proteosave 96F microplate digoxin
`showed the highest adsorption rate 34 and the adsorption rates of
`propranolol verapamil and paclitaxel were also over 10 14 18
`To an Enhanced Recovery plate and a NoBinding plate the adsorption
`rates of verapamil were over 10 18 27 and the adsorption rate of
`to an Enhanced Recovery plate was slightly over 10 To a
`showed an adsorption rate over 10 15 and the
`Plate+ paclitaxel
`adsorption rates of propranolol and digoxin were slightly over 10
`
`paclitaxel
`
`25 Analytical methods
`
`of each drug was measured with a HPLC system
`The concentration
`LC 10A Shimadzu A reverse phase column Capcell PAK C18 MG II
`20 mm id x 50 mm Shiseido was used The mobile phase consisted
`two components A 008 vol
`trifluoroacetic acidwater B
`of
`acetonitrile The flow rate was 060 mLmin and a linear gradient
`from 3 B to 70 B for 5 min was used The temperatures of the
`autosampler and column were 4°C and 40 °C respectively and the
`injection volume was 40 µL Detection of each drug was performed via
`UV absorption as follows 230 nm for propranolol
`and
`paclitaxel
`verapamil 243 nm for digoxin 258 nm for chloroquine 282 nm for
`warfarin and 304 nm for methotrexate
`
`Table 1
`Physicochemical properties and oral absorption rates of the probe drugs
`
`Drugs
`
`Methotrexate
`
`Warfarin
`
`chloroquine
`
`Propranolol
`
`Verapamil
`
`Digoxin
`
`Pachtaxel
`
`Solubility in water
`mgimL
`
`90h
`
`0019`
`
`00311
`
`00082r
`
`0065g
`
`000041h
`
`Charge
`
`Negative
`
`Negative
`
`Positive
`
`Positive
`
`Positive
`
`Neutral
`
`Neutral
`
`Absorption
`
`5
`
`70 Glass°
`<10°
`55
`60
`70°
`
`Data are from Nanying et al 2002 bBrigitte et al 2000 Logone
`Kulpin ski 2006Gea1y et at 1983BergstrOm 2003 gYa lkows Icy
`°Elizabeth
`1992 hHiroki et at 2006
`
`Rubessa
`
`2005
`
`Da nne nfelser
`
`

`

`T Fukazawa etal Journal of Pharmacological and Toxicological Methods 612010 329333
`
`331
`
`x M
`
`ethotrexate
`
`A Chlorequine
`10 Verapamil 0 Digoxin
`
`0Warfarin
`
`Propranolol
`
`Paclifaxel
`
`1
`
`2
`Time hr
`
`3
`
`4
`
`80
`
`70
`
`60
`
`50
`
`oe 40
`
`o`30
`
`20
`
`10
`
`0
`
`10
`
`0
`
`o<
`
`Multichem Microplate
`_ Proteosave 96F Plate
`0 Enhanced Recovery Plate
`Ea NoBinding Plate
`0 Plate+
`
`n
`
`isc
`
`14`b
`
`4b
`
`4ocK
`
`6
`
`4
`
`a°
`<z
`oq
`ec
`
`sc
`
`a
`9
`vkr°
`
`Compounds
`
`80
`
`70
`
`60
`
`50
`
`40
`
`30
`
`20
`
`10
`
`0
`
`C_
`
`6o
`
`Fig 1 Time course of the NSA of probe drugs on a conventional polystyrene microplate
`incubated at 4 C
`
`33 Effects of amphiphilic organic solvents on the NSA to a polypropylene
`
`microplate
`
`Fig 3 The NSA to low adsorption microplates incubated at 4 C The dotted line shows
`the mean ± SD of the adsorption rate from 2 to
`our target value Each data
`4 h after incubation
`
`represents
`
`solvents on the NSA to a con
`The effects of amphiphilic organic
`using methanol
`ventional polypropylene microplate were investigated
`and acetonitrile as the solvents The mean adsorption rates of the probe
`of aqueous methanol or
`drugs dissolved
`in various
`concentrations
`aqueous acetonitrile are summarized in Figs 4 and 5 respectively
`The mean adsorption rates of probe drugs decreased inversely with
`of methanol or acetonitrile With 20 methanol only
`the concentration
`exceeding 10 and with 30 or more
`showed adsorption
`the probe drugs almost disappeared
`In the case of acetonitrile a reduction in the adsorption was
`observed at lower concentrations
`than methanol
`the adsorption of all
`the probe drugs almost disappeared at 20 acetonitrile but the peak
`shapes of methotrexate and chloroquine at 20 or higher concentra
`tions of acetonitrile were broadened and split
`
`paclitaxel
`
`methanol
`
`the adsorption of all
`
`The mean adsorption rates of the probe drugs to coated or non coated
`microplates are summarized in Fig 6 To the non coated tissue culture
`and
`treated polystyrene microplate verapamil propranolol paclitaxel
`chloroquine were adsorbed at 65 57 32 and 23 respectively
`TEOS
`did not reduce the adsorption of the above drugs to below 10 VTMS did
`not reduce the adsorption of verapamil propranolol or paclitaxel below
`to about 10
`10 either but
`reduced the adsorption of chloroquine
`GPTMS effectively suppressed the adsorption of all
`the probe drugs and
`rate was 96 for paclitaxel AATMS also
`the maximum adsorption
`effectively suppressed the adsorption of almost all
`the probe drugs but
`increased the adsorption for methotrexate to 31
`
`4 Discussion
`
`34 Effects of coatings on the NSA to a tissue culture treated polystyrene
`
`microplate
`
`on the NSA to a tissue
`The effects of low adsorption coatings
`culture treated polystyrene microplate were investigated
`coupling agents as the coating agents
`
`using silane
`
`commonly seemed to be hydro
`The surface of plastic microplates
`phobic and the NSA to a microplate was also considered to be mainly
`mediated by a hydrophobic
`interaction between the hydrophobic surface
`of the microplate and also the hydrophobic
`surface of a compound Joni et
`al 2006 This idea appears to be acceptable in the case of conventional
`because hydrophobic
`paclitaxel verapamil and
`plastic microplates
`
`80
`
`70
`
`60
`
`50
`
`Water
`0 10 Methanol
`D 20
`30
`lig 40
`
`I=
`
`40
`
`0ci
`
`cc
`
`30
`
`20
`
`10
`
`0
`
`ItL1
`
`01
`
`c16
`
`As
`
`I 9ir
`
`As
`
`AT6
`
`Compounds
`
`Compounds
`
`A4
`
`rtess
`
`9e
`
`Glass Vial
`0 Polypropylene Microplate
`0 Polystyrene Microplate
`
`80
`
`70
`
`60
`
`130
`
`201
`
`10
`
`0
`
`E 4
`
`<
`
`Fig 2 The NSA to conventional polystyrene and polypropylene microplates and glass
`vials incubated at 4 C The dotted line shows our target value Each data
`mean ± SD of the adsorption rate from 2 to 4 h after incubation
`
`represents
`
`the
`
`Fig 4 Effect
`of methanol on the NSA to a conventional
`polypropylene microplate
`incubated at 4 C The dotted line shows our
`target value Each data
`mean ± SD of the adsorption rate from 2 to 4 h after incubation
`
`represents
`
`the
`
`

`

`332
`
`T Fukazawa etal Journal of Pharmacological and Toxicological
`
`Methods 612010 329333
`
`microplates have hydrophilic surfaces and showed weak adsorption
`to neutral and hydrophobic drugs However
`the adsorption of
`positively charged and hydrophobic verapamil on the Proteosave
`96F Plate Enhanced Recovery Plate and NoBinding Plate which were
`made from polystyrene was not
`reduced compared
`to that of the
`conventional
`polystyrene microplate The hydrophilic groups
`duced on the surfaces of these microplates were negatively charged
`so ionic adsorption remained and
`hydroxyl carbonyl or carboxyl
`played a role to adsorb positively charged verapamil
`It was reported that the NSA to a polystyrene plate was reduced if
`salts Joni et al 2006 so with salt solutions
`the solvent contained
`low adsorption microplates would greatly reduce the NSA
`Among these microplates the NoBinding
`plate and Plate+ reduced
`the probe drugs below 15 These values were
`the adsorption of all
`than the
`for our target value but would be more useful
`others tested
`
`these
`
`insufficient
`
`intro
`
`of
`
`the probe drugs
`
`With amphiphilic organic solvents the NSAs of all
`were effectively inhibited from a low concentration 10 20 of the
`solvents The inhibitory effects of acetonitrile on the NSA were
`stronger than those of methanol but
`the retention of drugs to the
`at 20 or higher concentrations
`analytical column was weakened
`acetonitrile Therefore aqueous methanol is a more preferable solvent
`for new chemical entities of which the physicochemical
`properties are
`unknown
`In the above conditions
`although aqueous
`solvents
`organic
`were still more hydrophilic than the plastic containers the NSAs of
`the probe drugs to the containers were well
`inhibited Considering
`the above results eliminating the difference
`in hydrophobicity or
`is not necessary but
`hydrophilicity between containers and solvents
`rather narrowing the difference is sufficient to reduce the NSA
`Whereas
`aqueous organic
`for analytical use
`solvents are useful
`they are limited in cell based assays because of their toxicity Donna
`et al 2008 William Joseph Charles 1998 Therefore to reduce the
`in hydrophilicity of the solvents and containers instead of
`difference
`
`increasing the hydrophobicity of the solvent decreasing the hydro
`phobicity of the container may be viable To do this we used some
`silane coupling agents to coat the surface of the tissue culture treated
`
`that contain
`
`microplate
`agents are silicon based chemicals
`Silane coupling
`two moieties one is a hydrolysable alkoxy group such as methoxy
`ethoxy or acetoxy and another is an organofunctional group such as
`amino methacryloxy or epoxy etc The alkoxy groups of silane
`coupling agents are hydrolyzed to silanols and they condense with
`hydroxyl groups on materials Their silanol groups also react with
`each other to give a tight siloxane network with their organofunc
`tional groups facing outward so the surface of the material shows the
`properties derived from the organofunctional groups
`physicochemical
`Gerald 1993
`Among the silane coupling agents we used only VTMS has a
`hydrophobic organofunctional group and the surface of the coated
`enhance
`microplate repelled water
`Its hydrophobicity will
`the
`adsorption to neutral and hydrophobic drugs such as paclitaxel and
`digoxin whereas it may decrease the ionic interaction to positively
`TEOS has no
`and verapamil
`charged
`chloroquine
`propranolol
`organofunctional group and the surface of the coated microplate has
`is ionized in water and the surface of the
`free silanol groups Silanol
`coated microplate is hydrophilic and negatively charged so the
`adsorption of hydrophilic and positively charged chloroquine may be
`enhanced Meanwhile the coating of TEOS seemed to be insufficient
`lacks an
`to prevent the adsorption of hydrophobic drugs because it
`organofunctional group which prevents
`the adsorption of hydropho
`bic drugs to the microplate
`and AATMS which have a hydrophilic organofunctional
`GPTMS
`the adsorption of almost all
`group inhibited
`the probe
`drugs
`effectively but only AATMS enhanced the adsorption of a negatively
`charged hydrophilic drug methotrexate This may be caused by the
`
`Water
`to Acetnitrile
`020
`0 30
`
`80
`
`70
`
`60
`
`50
`
`40
`
`30
`
`20
`
`Adsorption
`
`10 r
`
`o LAM=
`
`NS2
`
`4b
`
`t0`4to 4 °c
`
`<°
`09
`
`Q
`
`cz
`co
`4
`
`e
`
`P
`
`40
`
`Ze
`
`Compounds
`
`Fig 5 Effect of acetonitrile on the NSA to a conventional
`polypropylene microplate
`incubated at 4 C The dotted line shows our
`target value Each data
`mean ± SD of the adsorption rate from 2 to 4 h after incubation
`
`represents
`
`the
`
`digoxin showed high adsorption
`
`rates to the microplates However
`
`to
`
`tissue culture treated microplates in addition to the hydrophobic
`interaction an ionic interaction may play a role on the NSA because
`positively charged verapamil and propranolol showed higher adsorption
`The
`than that of electrically neutral but more hydrophobic paclitaxel
`used in this study was treated with
`tissue culture treated microplate
`corona which introduced hydrophilic groups like hydroxyl carbonyl and
`carboxyl groups to the surface of the plate Juliana et al 1997 Therefore
`its surface was negatively
`charged like glass and adsorbed positively
`charged drugs On the other hand the introduction of hydrophilic groups
`on the tissue culture microplate by corona treatment was sparse so the
`interaction remained and adsorbed hydrophobic drugs
`hydrophobic
`These tissue culture treatments
`are used
`low adsorption
`BD Biosciences 2002 so the
`treatments for plastic
`containers
`same adsorption characteristics as
`those of
`the tissue culture
`microplate were seen among the low adsorption microplates except
`for the MultichemTM microplate which was made from fluoride
`containing plastic The surface of the Multichem
`microplate was
`and
`like polytetrafluoroethylene
`consequently
`hydrophobic
`adsorbed hydrophobic drugs Yaqi et al 2003 Other low adsorption
`
`as
`
`it
`
`80
`
`IN Tissue Culture Treated Polystyrene Microplate
`70 o TEOS
`o VTMS
`gl GPTMS
`60 0 AATMS
`
`ill
`
`li
`
`i
`
`wth II
`kA
`
`k
`
`qoe
`
`442
`
`Compounds
`
`50
`
`r
`
`40F
`
`30
`
`20 F
`
`Adsorption
`
`101
`0t n
`
`Fig 6 Effect of low adsorption coatings on the NSA to a tissue culture treated micro
`plate incubated at 4 C The dotted line shows our target value Each data
`the mean ± SD of the adsorption rate from 2 to 4 h after incubation
`
`represents
`
`

`

`T Fukazawa
`
`333
`
`et al Journal of Pharmacological and Toxicological Methods 612010 329333
`Di S Li fen H Jessie L S A U 1995 Binding of Taxol
`
`similar fashion
`
`interaction of the amide group of AATMS and the carboxyl groups of
`methotrexate GPTMS also has a hydrophilic glycidoxy group but the
`adsorption of positively charged drugs was not enhanced
`It was
`the surface of GPTMS treated glass was electrically
`reported that
`neutral and hydrophilic Rohit Kenneth 82 Arun 2006 so the surface
`of a microplate coated with GPTMS will be neutral and hydrophilic
`and therefore it
`reduced the adsorption of all
`the probe drugs In a
`to GPTMS coatings with neutral and hydrophilic
`groups such as ether methacryl and acryl groups would reduce the
`adsorption of compounds with a wide range of surface properties
`GPTMS could coat a conventional
`polystyrene microplate but the
`reduction in the NSA was insufficient data not shown A small
`amount of a hydroxyl group can be introduced on the surface of a
`microplate during electron beam sterilization which is widely used
`for sterilization of plastic materials but it seems to be an insufficient
`scaffold for silanol groups of GPTMS Therefore to coat a conventional
`coupling agents we
`should
`non treated microplate with silane
`the amount of hydroxyl groups
`on the
`increase
`surface of
`the
`microplate While there are many methods to introduce hydroxyl
`groups on the surface of plastics such as UV electronic beams and
`82 Philippe
`atmospheric pressure plasma Claire Christelle Pascal
`2006 Nobuyuki 2005 UV radiation by a low pressure mercury lamp
`would be the most convenient method for laboratory use Halina
`Jolanta Aleksandra 82 Alina 2002
`the NSA is driven by
`In summary we have demonstrated that
`hydrophobic and ionic interactions and it could be reduced to an
`acceptable level by reducing these interactions
`On conventional
`plastic microplates the NSA is mainly driven by
`hydrophobic interactions but on tissue culture microplates and low
`
`adsorption microplates in addition to hydrophobic interactions ionic
`interactions play a role in the NSA Therefore to reduce the NSA to
`plastic containers both hydrophobic and ionic interaction should be
`reduced using amphiphilic organic
`solvents or neutral and hydro
`philic coatings
`
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`Donna A V Ebenezer B A Christopher D E Suresh D Ramana S U Mansoor A K
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`AAPS Journal 10 360
`Elizabeth Kulpinski 2006 Adaptive Focused Acoustics Presentation given at The
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