Quantitative Analysis of Molecular Absorption into PDMS Microfluidic Channels

Microfluidic devices fabricated using poly(dimethylsiloxane) (PDMS) polymer are routinely used for in vitro cell culture for a wide range of cellular assays. These assays typically involve the incubation of cultured cells with a drug molecule or a fluorescent marker while monitoring a cellular response. The accuracy of these assays depends on achieving a consistent and reproducible concentration of solute molecules in solution. However, hydrophobic therapeutic and fluorescent molecules tend to diffuse into the PDMS walls of the microfluidic devices, which reduce their concentration in solution and consequently affect the accuracy and reliability of these assays. In this paper, we quantitatively investigate the relationship between the partition coefficient (log P) of a series of markers routinely used in in vitro cellular assays including [3H]-dexamethasone, [3H]-diazepam, [14C]-mannitol, [3H]-phenytoin, and rhodamine 6G and their absorption into PDMS microfluidic channels. Our results show that the absorption of a given solute into PDMS depends on the hydrophilic/hydrophobic balance defined by its log P value. Specifically, results demonstrate that molecules with log P less than 2.47 exhibit minimal absorption (<10%) into PDMS channels whereas molecules with log P larger than 2.62 exhibit extensive absorption (>90%) into PDMS channels. Further investigations showed that TiO2 and glass coatings of PDMS channels reduced the absorption of hydrophobic molecules (log P > 2.62) by 2- and 4.5-folds, respectively.

[1]  B. Sellergren,et al.  Determination of phenytoin in plasma by molecularly imprinted solid-phase extraction. , 2001, Journal of chromatography. A.

[2]  Hyeon-Bong Pyo,et al.  A polymer-based microfluidic device for immunosensing biochips. , 2003, Lab on a chip.

[3]  R Hori,et al.  Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. , 1992, The Journal of biological chemistry.

[4]  M. Rowland,et al.  Modulation of the Permeability of H 2 Receptor Antagonists Cimetidine and Ranitidine by P-Glycoprotein in Rat Intestine and the Human Colonic Cell Line Caco-21 , 1998 .

[5]  Aaron R Wheeler,et al.  A circular cross-section PDMS microfluidics system for replication of cardiovascular flow conditions. , 2010, Biomaterials.

[6]  A Manz,et al.  Chemical amplification: continuous-flow PCR on a chip. , 1998, Science.

[7]  M. Raggi,et al.  Benzodiazepine metabolism: an analytical perspective. , 2008, Current drug metabolism.

[8]  M. Eigen,et al.  Techniques for single molecule sequencing , 1997, Bioimaging.

[9]  Shuichi Takayama,et al.  Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems , 2007, Proceedings of the National Academy of Sciences.

[10]  N. Voelcker,et al.  Recent developments in PDMS surface modification for microfluidic devices , 2010, Electrophoresis.

[11]  W. Löscher,et al.  Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein , 2007, Neuropharmacology.

[12]  Andreas Manz,et al.  Planar glass chips for capillary electrophoresis: repetitive sample injection, quantitation, and separation efficiency , 1993 .

[13]  A. Abate,et al.  Glass coating for PDMS microfluidic channels by sol-gel methods. , 2008, Lab on a chip.

[14]  F. Lombardo,et al.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. , 2001, Advanced drug delivery reviews.

[15]  A. Manz,et al.  Glass chips for high-speed capillary electrophoresis separations with submicrometer plate heights , 1993 .

[16]  B. Dunn,et al.  Oxygen diffusion in poly(dimethyl siloxane) using fluorescence quenching. I. Measurement technique and analysis , 1986 .

[17]  Noam Agmon,et al.  Structure and energetics of the hydronium hydration shells. , 2007, The journal of physical chemistry. A.

[18]  J. Emsley.  Very strong hydrogen bonding , 1980 .

[19]  Igor V. Tetko,et al.  Virtual Computational Chemistry Laboratory – Design and Description , 2005, J. Comput. Aided Mol. Des..

[20]  A. Leo,et al.  Partition coefficients and their uses , 1971 .

[21]  Hongseok Moses Noh,et al.  Microfluidic platform for hepatitis B viral replication study , 2008, Biomedical microdevices.

[22]  L. Beda.  Thermal physics , 1994 .

[23]  Corwin Hansch,et al.  Comprehensive medicinal chemistry : the rational design, mechanistic study & therapeutic application of chemical compounds , 1990 .

[24]  A Scherer,et al.  A microfabricated device for sizing and sorting DNA molecules. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[25]  P Ravi Selvaganapathy,et al.  Microfluidic devices for cell based high throughput screening. , 2010, Lab on a chip.

[26]  R. Nuzzo,et al.  Microfluidic devices for culturing primary mammalian neurons at low densities. , 2007, Lab on a chip.

[27]  Xiao-dong Liu,et al.  Increased P-glycoprotein function and level after long-term exposure of four antiepileptic drugs to rat brain microvascular endothelial cells in vitro , 2008, Neuroscience Letters.

[28]  L J Kricka,et al.  Degenerate oligonucleotide primed-polymerase chain reaction and capillary electrophoretic analysis of human DNA on microchip-based devices. , 1998, Analytical biochemistry.

[29]  D. Beebe,et al.  PDMS absorption of small molecules and consequences in microfluidic applications. , 2006, Lab on a chip.

[30]  C. Culbertson,et al.  Surface engineering of poly(dimethylsiloxane) microfluidic devices using transition metal sol-gel chemistry. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[31]  C. Effenhauser,et al.  Integrated capillary electrophoresis on flexible silicone microdevices:  analysis of DNA restriction fragments and detection of single DNA molecules on microchips. , 1997, Analytical chemistry.

[32]  C. Henry,et al.  Generation of hydrophilic poly(dimethylsiloxane) for high-performance microchip electrophoresis. , 2006, Analytical chemistry.

[33]  Brian N. Johnson,et al.  An integrated nanoliter DNA analysis device. , 1998, Science.

[34]  K. Helle,et al.  The fluorescent cationic dye rhodamine 6G as a probe for membrane potential in bovine aortic endothelial cells. , 1999, Analytical biochemistry.

[35]  D. J. Harrison,et al.  Micromachining of capillary electrophoresis injectors and separators on glass chips and evaluation of flow at capillary intersections , 1994 .

[36]  C Gärtner,et al.  Polymer microfabrication methods for microfluidic analytical applications , 2000, Electrophoresis.

[37]  L J Kricka,et al.  Chip PCR. II. Investigation of different PCR amplification systems in microbabricated silicon-glass chips. , 1996, Nucleic acids research.

[38]  M. Rowland,et al.  Modulation of the permeability of H2 receptor antagonists cimetidine and ranitidine by P-glycoprotein in rat intestine and the human colonic cell line Caco-2. , 1999, The Journal of pharmacology and experimental therapeutics.

[39]  Jeong‐Yeol Yoon,et al.  Reusable, polyethylene glycol-structured microfluidic channel for particle immunoassays , 2009, Journal of biological engineering.

[40]  R A Mathies,et al.  Optimization of high-speed DNA sequencing on microfabricated capillary electrophoresis channels. , 1999, Analytical chemistry.

[41]  R A Mathies,et al.  High-throughput genetic analysis using microfabricated 96-sample capillary array electrophoresis microplates. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[42]  M Wessling,et al.  Membranes and microfluidics: a review. , 2006, Lab on a chip.

[43]  M. E. Cox,et al.  Oxygen diffusion in poly(dimethyl siloxane) using fluorescence quenching. II: Filled samples , 1986 .

[44]  J. Proudfoot,et al.  The evolution of synthetic oral drug properties. , 2005, Bioorganic & medicinal chemistry letters.

[45]  Shuichi Takayama,et al.  Small volume low mechanical stress cytometry using computer-controlled Braille display microfluidics. , 2007, Lab on a chip.

[46]  W. Stigelman,et al.  Goodman and Gilman's the Pharmacological Basis of Therapeutics , 1986 .

[47]  P. Friden,et al.  Transdermal and intradermal iontophoretic delivery of dexamethasone sodium phosphate: quantification of the drug localized in skin , 2009, Journal of drug targeting.

[48]  Dhananjay Bodas,et al.  Formation of more stable hydrophilic surfaces of PDMS by plasma and chemical treatments , 2006 .

[49]  D. J. Harrison,et al.  Capillary electrophoresis and sample injection systems integrated on a planar glass chip , 1992 .

[50]  B. Berne,et al.  Structure and energetics of Xe−n , 1988 .

[51]  Dong Pyo Kim,et al.  Silicate glass coated microchannels through a phase conversion process for glass-like electrokinetic performance. , 2011, Lab on a chip.

[52]  Michał R. Radowski,et al.  Influence of nanocarrier type and size on skin delivery of hydrophilic agents. , 2009, International journal of pharmaceutics.

[53]  C. Kittel,et al.  Thermal Physics, 2nd ed. , 1998 .

[54]  T. Ishikawa,et al.  In vitro blood flow in a rectangular PDMS microchannel: experimental observations using a confocal micro-PIV system , 2008, Biomedical microdevices.

[55]  A. Woolley,et al.  Ultra-high-speed DNA sequencing using capillary electrophoresis chips. , 1995, Analytical chemistry.

[56]  M. Leider.  Goodman & Gilman's The Pharmacological Basis of Therapeutics , 1985 .

[57]  G. R. Facer,et al.  Capacitance cytometry: measuring biological cells one by one. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[58]  Abel L. Thangawng,et al.  An ultra-thin PDMS membrane as a bio/micro–nano interface: fabrication and characterization , 2007, Biomedical microdevices.

[59]  G. Whitesides,et al.  Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane). , 1998, Analytical chemistry.

[60]  Masami Niwa,et al.  Permeability Studies on In Vitro Blood–Brain Barrier Models: Physiology, Pathology, and Pharmacology , 2005, Cellular and Molecular Neurobiology.

[61]  M. A. Northrup,et al.  A miniature analytical instrument for nucleic acids based on micromachined silicon reaction chambers. , 1998, Analytical chemistry.

[62]  G. Whitesides,et al.  Solvent compatibility of poly(dimethylsiloxane)-based microfluidic devices. , 2003, Analytical chemistry.

[63]  S. Fowler,et al.  Application of Nile red, a fluorescent hydrophobic probe, for the detection of neutral lipid deposits in tissue sections: comparison with oil red O. , 1985, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[64]  R. Schmelzeisen,et al.  Prevention of postoperative swelling and pain by dexamethasone after operative removal of impacted third molar teeth , 2004, European Journal of Clinical Pharmacology.

[65]  R. Boudreau.  Foreword contributions from the 50th electronic components and technology conference , 2001 .

[66]  L. Rebenklau,et al.  Realization of hybrid microfluidic systems using standard LTCC process , 2000, 2000 Proceedings. 50th Electronic Components and Technology Conference (Cat. No.00CH37070).

[67]  L J Kricka,et al.  Chip PCR. I. Surface passivation of microfabricated silicon-glass chips for PCR. , 1996, Nucleic acids research.

[68]  Jian Zhang,et al.  Polymerization optimization of SU-8 photoresist and its applications in microfluidic systems and MEMS , 2001 .

[69]  I. Rajta,et al.  Fabrication of optical devices in poly(dimethylsiloxane) by proton microbeam , 2010 .

[70]  Patrick M. Pilarski,et al.  Small volume PCR in PDMS biochips with integrated fluid control and vapour barrier , 2006 .

[71]  G. Whitesides,et al.  Fabrication of microfluidic systems in poly(dimethylsiloxane) , 2000, Electrophoresis.

[72]  John P. Puccinelli,et al.  Thermal aging and reduced hydrophobic recovery of polydimethylsiloxane , 2006 .

[73]  S. Jacobson,et al.  Multiple sample PCR amplification and electrophoretic analysis on a microchip. , 1998, Analytical chemistry.

[74]  C. Noe,et al.  Validation of in vitro cell culture models of the blood-brain barrier: tightness characterization of two promising cell lines. , 2008, Journal of pharmaceutical sciences.

[75]  L J Kricka,et al.  Analysis of ligase chain reaction products amplified in a silicon-glass chip using capillary electrophoresis. , 1996, Journal of chromatography. A.

[76]  L. Goodman,et al.  The Pharmacological Basis of Therapeutics , 1941 .