Design of switchable "smart" surfaces for biomedical and nanotechnological applications

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, June 2005.Includes bibliographical references.Chapter 1. An Introduction to Self-Assembled Monolayers & Surface Characterization A brief summary of the formation, structure, and characterization techniques of self assembled monolayers (SAMs) is described. The characterization techniques include contact angle goniometry, ellipsometry, grazing-angle Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV), sum-frequency generation spectroscopy (SFG), and atomic force microscopy (AFM). Chapter 2. A Reversibly Switching Surface The design of surfaces that exhibit dynamic changes in interfacial properties such as wettability in response to an electrical potential is described. The change in wetting behavior was caused by surface-confined, single-layered molecules undergoing conformational transitions between a hydrophilic and a moderately hydrophobic state. Reversible conformational transitions were confirmed both at a molecular level using sum-frequency generation spectroscopy and at a macroscopic level using contact angle measurements. This type of surface design enables amplification of conformational transitions at a molecular level to macroscopic changes in surface properties without altering the chemical identity of the surface. Such reversibly switching surfaces may open new opportunities in interfacial engineering.Chapter 3. A Synthetic Chemical Route for the Formation of Homogeneously- Mixed Self-Assembled Monolayers A novel way to produce self-assembled monolayers (SAMs) uniformly mixed on the molecular length scale is described.(cont.) Initially, a precursor SAM was formed from molecules that are derived from 16-mercaptohexadecanoic acid (MHA) and contain a globular end group. Self-assembly of these molecules resulted in a SAM that is densely packed with respect to the space-filling end groups, but shows low-density packing with respect to the hydrophobic chains. Subsequent cleavage of the space-filling end groups established a low-density SAM of MHA. A mixed monolayer of MHA and n-butanethiol was formed by backfilling the low-density monolayer of MHA with the corresponding alkanethiol. The new "mixed" SAM was characterized by optical ellipsometry, contact angle goniometry, X-ray photoelectron spectroscopy (XPS), Fourier Transform Infrared Spectroscopy (FT-IR), cyclic voltammetry (CV), and reductive desorption voltammetry. The results indicate a uniformly mixed monolayer as compared to a SAM generated by coadsorption of mixtures of the same MHA and n-butanethiol molecules. This approach provides a way to produce SAMs that are uniformly mixed using a synthetic chemical route, which affords considerable flexibility in composition and also in the ratio of the different molecules in the mixed SAM. Chapter 4.(cont.) Design of Oligonucleotide Arrays Using Homogeneously Mixed Self - Assembled Monolayers We have employed two quantitative techniques, quart-crystal microbalance with dissipation monitoring (QCM-D) and surface plasmon resonance imaging (SPR) to quantify the hybridization efficiency of a 25-mer oligonucleotide probe to two different surfaces: a dense 16-mercaptohexadecanoic acid self-assembled monolayer (MHA SAM) and a homogeneously-mixed (HM) SAM generated from the method described in Chapter 3 that allows for regular spacing of functional -COOH groups. This reduced density of functional groups led to reduced attachment of oligonucleotide probes to the surface, increasing the area per probe, and allowed more space in which complimentary sequence can bind. Reducing the density of immobilized probes led to the improvement in hybridization efficiency as demonstrated in both SPR and QCM-D results, which are comparable to previous reports. Our method paves the way for customizing binding efficiency and target probe density based on the distance between functional groups. By changing the headgroup size of the precursor monolayer, different distances between functional group can be formed, allowing for an ability to tailor distances between molecules. This method may allow for improvement in DNA array technology.Chapter 5. Long-Term Stability of Self-Assembled Monolayers in Biological Media The study of long term stability of self-assembled monolayer (SAM) in biological media is of importance in evaluating its usefulness for applications in implantable biochips, biosensors, or biological microelectromechanical system (bioMEMs) devices for drug delivery.(cont.) To minimize biofouling effects, researchers have investigated protein/cell adhesion resistant surface-bound materials such as poly(ethylene glycol) or oligo(ethylene glycol) terminated self-assembled monolayers. However, no long term study in biological media has been done. To address the issue of moderate to long-term stability of SAMs for bioMEMS device modification, alkanethiol and oligo(EG) terminated alkanethiol monolayers were prepared and studied after immersion in either phosphate buffer saline (PBS) or calf serum. Here, undecanethiol (CllH23SH) and tri(ethylene glycol) terminated undecanethiol (HO(C2H40)3C H22SH) self-assembled monolayers (SAMs) on clean gold surfaces were prepared and characterized. The SAMs were then immersed into either phosphate buffered saline (PBS) or calf serum. The SAM samples were emmersed and investigated using several analytical techniques at numerous points over the next 35 days. Contact angles and current densities in voltammetry changed dramatically for the PBS samples over the time period, particularly after 21 days. Results indicate substantial loss of the integrity of the SAM. Similar alterations with time were observed for the calf serum samples in both contact angle and voltammetry measurements. X-ray photoelectron spectroscopy indicates that the likely origin is desorption of the alkanethiol moiety as evidenced by appreciable loss of the S 2p signal after 35 days. Additionally, this work may serve as a starting point for further studies of surface chemical modification methods for moderate to long-term minimization of biofouling for in vivo applications.by Thanh-Nga T. Tran.Ph.D