A novel biointerface bearing zwitterionic carboxybetaine moieties was developed for effective resistance to nonspecific adsorption of proteins and blood cells. Self-assembled thin films (SAFs) of (N
-dimethylaminopropyl) trimethoxysilane were formed as mattress layers by either vapor or solution deposition. Subsequently, the tertiary amine head groups on SAFs were reacted with β-propiolactone to give zwitterionic carboxybetaine moieties via in situ
synthesis. The optimal reaction time of 8 h for both preparation methods was verified by static contact angle measurements. According to the X-ray photoelectron spectroscopy, 67.3% of amine groups on SAFs prepared from the vapor deposition was converted to the zwitterionic structures after reaction of β-propiolactone. The antifouling properties of the zwitterionic biointerfaces were quantitatively evaluated in the presence of protein solutions using a quartz crystal microbalance with dissipation, showing a great improvement by factors of 6.5 and 20.2 from tertiary amine SAFs and bare SiO2
surfaces, respectively. More importantly, the zwitterionic SAFs were brought to contact with undiluted human blood in chaotic-mixer microfluidic systems; the results present their capability to effectively repel blood cell adhesion. Accordingly, in this work, development of carboxybetaine SAFs offers a facile yet effective strategy to fabricate biocompatible biointerfaces for a variety of potential applications in surface coatings for medical devices.