laser.qxp 3/17/2005 10:56 AM Page 1 LASER PROCESSING OF ADVANCED BIOMATERIALS Lasers are ideal for depositing diamondlike carbon films, microfabricating “lab-on-a-chip” biosensors, and building medical device nanostructures. Roger J. Narayan*, Chunming Jin, Tim Patz, Anand Doraiswamy Georgia Institute of Technology, Atlanta, Georgia Rohit Modi, Douglas B. Chrisey U.S. Naval Research Lab, Washington, D.C. Yea-Yang Su Amorphous Oxide Technology, Atlanta, Georgia S. J. Lin Veterans General Hospital, Taipei, Taiwan Aleksandr Ovsianikov, Boris Chichkov Laser Zentrum Hannover, Hannover, Germany ince their invention in the early 1960s, lasers have found many uses in the med- ical field. Most current medical applica- tions of lasers involve service as a “uni- Sversal scalpel” in minimally invasive surgeries, 1 µm which offer little contact, little blood loss, shorter operating times, and less postoperative pain than Fig. 1 — Top: scanning electron micrograph of anodized conventional techniques. Laser in situ ker- alumina membrane. Middle: scanning electron micrograph atomileusis (LASIK) refractive corneal surgery, of anodized alumina membrane exposed to platelet rich coagulation for retinal detachment, and skin treat- plasma. The surface exhibits significant protein adsorp- tion and pore fouling. Bottom: scanning electron micrograph ments are only some of the current applications of anodized diamondlike carbon-coated alumina membrane for lasers in medicine. exposed to platelet rich plasma. The surface contains sodium In the future, lasers will also serve to create chloride crystals; however, the pores remain free of the fouling novel medical devices with unique biological seen in the middle image. functionalities. Microstructured and nanostruc- tured biomaterials have recently been fabricated ical implants for over thirty years. The first carbon via pulsed laser deposition, laser direct writing, biomaterials were low-temperature isotropic (LTI) and two photon-polymerization processes. In this pyrolytic carbons. These dense, isotropic ma- article, we will review the current status of laser terials are deposited from a hydrocarbon gas in processing in the development of ceramic a fluidized-bed reactor at temperatures below nanocomposite films, tissue engineered ma- 1500ºC (2730°F). In 1969, Dr. De Bakey introduced terials, and nanostructured medical devices. a pyrolytic carbon-coated aortic valve prosthesis, which incorporated carbon-coated metal struts Diamondlike carbon thin films and a carbon-coated hollow ball. These carbon- Carbon biomaterials have functioned in med- coated valves demonstrated biocompatibility, in- *Member of ASM International ertness, and immunity to fatigue, and are the com- ADVANCED MATERIALS & PROCESSES/APRIL 2005 39 laser.qxp 3/24/2005 10:30 AM Page 2 Imaging that accelerates the release of silver ions. Several studies have shown that diamondlike carbon can greatly improve the hemocompati- Optical bility of a medical device. Figure 1 is a scanning Synchronized illumination laser electron micrograph of a diamondlike carbon- pulse coated anodized alumina membrane placed in UV transparent platelet-rich plasma. Unlike many metal or ribbon polymer surfaces, diamondlike carbon-coated Thin film, surfaces do not adsorb fibrous proteins or cellular < 200 nm µ material. In fact, only sodium chloride crystals z 50 m y were observed on the surface. In-vitro studies CAD/CAM motion-controlled x stage demonstrate that platelets are activated less often and platelets adhere less frequently on diamond- Fig. 2 — Left: schematic of matrix assisted pulsed laser evaporation-direct like carbon-coated surfaces than on titanium, ti- write (MAPLE-DW) system. Right: confocal micrograph of MAPLE-DW trans- ferred B35 neuroblasts within an extracellular matrix scaffold. Axonal exten- tanium carbide, titanium nitride, or stainless steel sions were observed between neuroblasts on different deposition planes, which surfaces. Therefore, diamondlike carbon-coated were spaced 30 to 40 µm apart. materials are being considered for a variety of blood-contacting medical devices, including im- Beam expander plantable microdevices, sensors, coronary artery Near IR fs pulses stents, synthetic heart valves, left-ventricular as- Femtosecond (fs) oscillator sist devices, and artificial hearts. Scanner Matrix-assisted pulsed laser evaporation z CCD camera Matrix-assisted pulsed laser evaporation- y Ormocer direct write (MAPLE-DW) is a novel technique for micrometer-scale resolution transfer of small x amounts (one pico-liter) of polymers, proteins, Immersion liquid and eukaryotic cells. The MAPLE-DW system Mask contains an excimer laser, biomaterial-seeded quartz disk, and a computer-controlled X-Y trans- Glass plate lation stage (Fig. 2). Structure Near IR fs pulses The biomaterial is solvated in a transparent ma- trix and spin-coated onto a quartz disk. The bio- material-seeded quartz disk is then placed in a Fig. 3 — Left: schematic of two photon polymerization system. Right: schematic position such that the biomaterial-coated side of laser orientation in two photon polymerization system. faces the substrate. A lens then focuses the laser ponents of choice to this day. More recently, di- pulse at the biomaterial/quartz disk interface. A amondlike carbon has been considered for med- low-fluence (low-energy) ArF laser pulse (l=193 ical prostheses and surgical instruments. nm, fluence=0.01-0.5 mJ/cm2) volatilizes some of Although no universally accepted nomencla- the matrix and propels the material from the bio- ture has been agreed upon, the term “diamond- material-seeded ribbon to the underlying sub- like carbon” (DLC) often refers to amorphous strate. The computer-controlled X-Y translation carbon thin films containing some sp3 hybridized stage enables a resolution of one micrometer. atoms. These materials exhibit atomic number Laser-based processing provides several ad- densities greater than 3.19 g/cm3, and often pos- vantages over inkjet, Langmuir-Blodgett, dip- sess densities closer to that of diamond (3.51 pen, and other solvent-based techniques. These g/cm3) than that of graphite (2.26 g/cm3). include: Diamondlike-carbon/metal-nanocomposite • Enhanced biomaterial-substrate adhesion. films demonstrate enormous potential for med- • Deposition can be carried out under ambient ical device coatings. Silver, platinum, titanium, conditions. and silicon have been incorporated into diamond- • The amount and location of transferred ma- like carbon films by a multi-target pulsed-laser terial can be quantitatively determined. deposition process. These composite films exhibit • Multilayered structures can be prepared with exceptional wear resistance, corrosion resistance, multiple quartz disks or segmented targets. and hardness, as well as improved adhesion to We have recently demonstrated three-dimen- medical alloys. sional transfer of B35 neuroblast cells by varying In addition, silver-platinum composite films the transfer energy and the extracellular matrix have shown unique antimicrobial properties, solidification. Neutral density filters attenuated which result from the release of silver ions. Silver the incident laser beam without significantly ions bind strongly to electron donor groups on changing the laser spot size. We initially deposited oxygen-, nitrogen-, or sulfur-containing enzymes, neuroblasts with a laser fluence capable of deeply and displace cations (e.g., Ca2+) necessary for en- penetrating the extracellular matrix. Another neu- zyme function. Films containing both silver and roblast array was then deposited directly on top platinum demonstrate enhanced antimicrobial of the initial array by attenuating the laser beam activity due to formation of a galvanic couple and lowering the laser fluence. This process was 40 ADVANCED MATERIALS & PROCESSES/APRIL 2005 laser.qxp 3/17/2005 10:57 AM Page 3 repeated several times, and resulted in a 100 µm thick ECM scaffold with neuroblasts located at Pulsed laser deposition various depths. Pulsed laser deposition (PLD) is a physical vapor deposition We envision several applications for the ma- process for creating diamondlike carbon thin films with high trix-assisted pulsed laser evaporation-direct write fractions of sp3 hybridized carbon atoms. A KrF (l=248 nm) or process in next generation medical devices: ArF (l=193 nm) laser is used to vaporize a target that contains • MAPLE-DW can create localized patterns of components of the desired film. When laser radiation is ab- enzymes, cells, or pharmacologic agents for im- sorbed by the target, electromagnetic energy is converted into plantable biosensors and drug delivery devices. electronic excitation, chemical energy, mechanical energy, and • MAPLE-DW can provide a unique approach thermal energy. These processes produce a plume of ionic, for fabricating customized three-dimensional cell- atomic, and molecular species with kinetic energies on the order seeded scaffolds for tissue engineering. of 100 to 1000 kT (2.5 to 25 eV), which propagates in a forward- peaked manner toward the substrate surface. Typical growth Two-photon polymerization rates of DLC films with the KrF laser (fluence=2-5 mJ/cm2) are We have recently demonstrated direct writing on the order of 0.01 nm/pulse. of three-dimensional medical device nanostruc- Deposition of diamondlike carbon films generally involves tures by two-photon polymerization (2PP). This ablation of a high-purity graphite target; other target materials technique involves the application of light to in- have included