255 Critical Reviews ™ in Biomedical Engineering, 43(4): 255-276 (2015) 0278-940X/15/$35.00 © 2015 by Begell House, Inc. Author Proof Atomic Layer Deposition in Bio-Nanotechnology: A Brief Overview Arghya K. Bishal, a Arman Butt, a Sathees K. Selvaraj, b Bela Joshi, b Sweetu B. Patel, a,c Su Huang, b Bin Yang, c Tolou Shukohfar, a,c Cortino Sukotjo, d & Christos G. Takoudis a,b, * a Department of Bioengineering, University of Illinois at Chicago, Chicago, IL; b Department of Chemical Engineering, University of Illinois at Chicago, Chicago, IL; c Department of Mechanical Engineering, Michigan Technological University, Houghton, MI; d Department of Restorative Dentistry, University of Illinois at Chicago, Chicago, IL *Address all correspondence to: Christos G. Takoudis, 218 SEO, MC 063 UIC BioE, 851 S. Morgan Street, Chicago, IL 60607; takoudis@uic.edu ABSTRACT: Atomic layer deposition (ALD) is a technique increasingly used in nanotechnology and ultrathin flm deposition; it is ideal for flms in the nanometer and Ångström length scales. ALD can efectively be used to modify the surface chemistry and functionalization of engineering-related and biologically important surfaces. It can also be used to alter the mechanical, electrical, chemical, and other properties of materials that are increasingly used in biomedical engineering and biological sciences. ALD is a relatively new technique for optimizing materials for use in bio-nanotechnology. Here, after a brief review of the more widely used modes of ALD and a few of its applications in biotechnology, selected results that show the potential of ALD in bio-nanotechnology are presented. ALD seems to be a promising means for tuning the hydrophilicity/hydrophobicity characteristics of biomedical surfaces, forming conformal ultrathin coatings with desirable properties on biomedical substrates with a high aspect ratio, tuning the antibacterial properties of substrate surfaces of interest, and yielding multifunctional biomaterials for medical implants and other devices. KEY WORDS: atomic layer deposition (ALD), bio-nanotechnology, hydrophilicity/hydrophobicity, multifunctional biomaterials I. INTRODUCTION Atomic layer deposition (ALD) is an increasingly important technique in nanotechnology and ultrathin- flm deposition down to a thickness of only a few Ångströms. ALD is a chemical deposition technique used to synthesize thin flms and modify surface chemistry and functionalization. Therefore it has a wide range of applications, from semiconductor processing to biomaterials surface enhancements. The ALD technique was developed in the 1960s and 1970s by 2 diferent research groups. In the 1960s the concept of ALD was frst introduced in Russia by Sveshnikova et al. 1 and was named “molecular layering.” In the 1970s the same technique was developed independently in Finland by Dr. Tuomo Suntola and his colleagues for electroluminescent displays, 2,3 which was extended into microelectronic industries and later in research related to nanoflm deposition that progressed to semiconductor materi- als. The motivation for use in semiconductors was the manipulation of the dielectric constant of thin- flm structures that could optimize their capacitance as needed. Microelectronic industries started using ALD commercially in the 2000s. In general, ALD is used to deposit any kind of ultrathin surface coating using a precursor, an oxidant, and an inert gas to purge unreacted molecules from the chamber between the precursor/oxidant steps. This process typically contains 4 steps in one cycle to deposit one monolayer of a desired coating onto the substrate of interest (Fig. 1). The growth rate of each cycle is calculated by the thickness of the flm formed per cycle. Since the flm is formed from a precursor and oxidant/linker (in the case of a metal oxide, for example), the thickness also depends on the size and physical properties of the precursor and the oxidant/linker. The duration of each cycle depends on the pulse duration set for the precursor, the oxidant, and purging. The frst step is the introduction of a precursor, which contains the element of interest with varying