Temperature-Responsive Polymers for Biological Applications

Water soluble polymers with tunable lower critical solution temperature (LCST) are of increasing interest for biological applications such as cell patterning, smart drug release, DNA sequencing etc. The present study addresses control of the polymer temperature response in water by varying chemical composition of the monomer. In order to achieve this a series of polymers were designed and synthesized based on an ethyleneoxide/ethylene monomer (EO/EE). Polymers were synthesized using polycondensation reactions of difunctional m-EO and n-EE oligomers. The cloud point follows linearly the balance of hydrophobic/hydrophilic interaction and can be tailored in the range of 7 70C by varying the m/n composition and polymer type. Polymer grafting onto the silicon surface exhibits similar solubility behaviour. Adhesion energy measurements show that grafted polymers have solubility cloud points at the temperatures that are close to the ones of the bulk polymer solutions. Advance of biological and medical research demand of intelligent polymer materials for applications such as smart and/or controlled drug delivery [1, 2, 3], controlled cell patterning [4, 5, 6], DNA separation and sequencing [7, 8] and others. Many such applications rely on smart polymer response to the external stimuli such as pH, temperature, irradiation [9]. For example Sauer et al. [10] reports synthesis of pH sensitive nanocontainers based on poly(acrylic acid) which show a reversible pH and ionic strength dependent swelling transition in water. Reported hydrodynamic radius change is from 45 nm to 195 nm when solution pH changes from 3 to 9. Zha et al. [11] report fabrication of temperature sensitive microcontainers based on crosslinked poly(N-isopropylacrylamide) (PNIPAM). Reported change of hydrodynamic diameter is from 450 nm to 250 nm with the LCST occuring at around 32 degrees. Buchholz et al. [8] report of DNA sequencing using poly(N,N-diethylacrylamide – co – N,N-dimethylacrylamide) matrixes that significantly change viscosity upon reaching phase transition temperature. Such thermaly controlled switch eanbles acceleration of microchannel flow by 3 orders of magnitude that allows for significant improvement of sequencing efficiency of DNA analysis. Cell patterning, biorecognition and biosensor technolgy rely on the interaction of synthetic material and biological surfaces. Surfaces that undergo rapid shifts in surface properties with small external changes are of particular interest [12]. Temperature – sensitive solubility usually originates from the existence of a lower critical solution temperature (LCST) beyond which the polymer becomes insoluble in water. Such behavior is typical for the polymers that form hydrogen bonds to water [12, 14]. Driven by the high promise for biomedical applications, polymers that exhibit a response in water at about 37oC are of particular interest. Taylor and Cerankowski [14] predicted that LCST of a water soluble polymer can be varied by controlling balance of hydrophilic and hydrophobic segments in the polymer chain. However, to date most polymers studied are based on a single homopolymer (PNIPAM), that exhibits LCST at 32C[15], and efforts to change its LCST mostly involved modifications through addition of hydrophobic branches [15, 16, 17]. These branched polymers exhibit cloud points (CP) that do not correlate with the hydrophobic/hydrophilic balance of the polymer[15]. This behavior originates from the branched molecular architecture of these materials, which results in a coil to micelle “phase transition”, rather than a polymer solution (LCST) phase transition. Bokias et al. [16] showed that increasing the length of the hydrophobic side chains can shift the LCST of PNIPAM, but now the phase transition broadens and occurs over a wide temperature range. Virtanen et al.[17], investigating PNIPAM modified with Report Documentation Page Form Approved OMB No. 0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden, to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE 00 JUN 2003 2. REPORT TYPE N/A 3. DATES COVERED 4. TITLE AND SUBTITLE Temperature-Responsive Polymers for Biological Applications 5a. CONTRACT NUMBER