Scanning relatively large samples with commercially available atomic force microscopes (AFM) often can be time-consuming because it is performed serially and because the scanning range is limited. Using lasers to detect cantilever deflection adds to the cost of the overall system and complicates the adjustment and exchange of the cantilevers, which contributes to the tedium of scanning. Newer methods can be integrated into AFM probes, and using an array of cantilevers can speed up scanning. Some researchers also have combined integrated detection with cantilever arrays, but these systems still require bulky desktop devices. A team at Swiss Federal Institute of Technology in Zurich has introduced a stand-alone, single-chip unit that contains everything necessary for AFM. As described in the Dec. 7 issue of PNAS, the chip has an array of cantilevers, each of which features actuation, detection, control, amplification and on-chip digital processing. Researchers have developed an AFM system that integrates the electronics and mechanical components on one chip. It enables increased scanning speeds and is much less expensive to manufacture than conventional systems. Courtesy of Swiss Federal Institute of Technology.Thus, no external controller is needed. Because everything is integrated on one chip, the system can scan at a much faster rate and can be much smaller and less expensive than many commercially available units and research prototypes.The most novel aspect of the system, said Andreas Hierlemann, the principal investigator in the study, is the high degree of system integration. Mechanical components, analog circuits and digital computing power are united on a single CMOS chip. Control operations are handled in a digital signal processor, the design of which provides for high computing power: 16 million arithmetic operations per second.The design leads to several additional advantages over other AFM systems. The first is that the compactness of the instrument allows the user to access samples much more easily, Hierlemann said, and the scanning site need not be reachable by a readout laser. Second, the array of scanning tips enables parallel scanning. Moreover, in serial mode, the cantilevers may be outfitted with various tips to fulfill different functions. The system is fabricated on a CMOS chip — a widely used technology for integrated circuits. The 10 × 7-mm chip contains an array of 10 scanning and two reference cantilevers, the latter on either end of the array. The scanning cantilevers are 500 × 85 × 5 μm; the reference cantilevers are the same width and thickness but only 250 μm long, so as to avoid contact with the sample surface. The cantilever deflection, resulting from the exertion of force upon the cantilever tip, is detected by four piezoresistors at the base of the array.The circuitry occupies most of the remaining area of the chip. A serial digital interface enables the chip to communicate via National Instruments’ LabView software, which makes it possible for the user to create applications employing the integrated electronics on the chip. The researchers encountered several challenges in designing the AFM system, primarily with respect to micromechanics. Manufacturing CMOS microelectronics is a common process and can be outsourced readily to silicon fabrication facilities, said Sadik Hafizovic, the first author of the study. But manufacturing micromechanics is far less established. As a result, they typically perform micromachining in-house after the microelectronics are finished, with an equipment budget that is probably only a fraction of what high-volume silicon labs invest in their line.Reliability and reproducibility become major issues, however, when micromachining components in the dimensions of the AFM system’s cantilevers. For this reason, the investigators prefabricated as much of the mechanical structures as possible, using the processes of CMOS fabs. For example, a doping process typically used to manufacture transistors with submicron dimensions defined the cantilevers. “In this way,” Hafizovic said, “the accuracy of the CMOS technology is transferred to micromachining.”To demonstrate the utility of the system, they employed it for two standard AFM applications: surface imaging and force-distance measurements. For the former, they operated the system in constant-force mode, in which the on-chip force controller measures and maintains the force acting on the cantilever as the tip is scanned over the sample surface. The actuation signal required to maintain the force provides the height information about the surface. They produced a variety of scanning images with the single-chip unit. Generally, they achieved a maximum scanning speed of approximately 1 mm/s and a vertical resolution of less than 1 nm. They noted that they could keep the force exerted on a sample as low as 5 nN to image soft samples.For the force-distance measurements, the on-chip controller handled the cantilevers’ movement toward and away from the sample surface, and the force on the cantilevers was recorded during this time. The researchers obtained force-distance measurements twice every second, calculating the resolution to be less than 1 nN.They attached spherical glass beads 20 μm in diameter to the ends of three cantilevers, providing a well-defined geometry on the surfaces to be in contact with the samples. The glass chips that they used as samples contained gold patterns coated with either a methyl- or an amino-terminated undecanethiol self-assembled monolayer. The results showed that the glass beads’ interactions with the sample surface were the most intense. Those with the amino-terminated self-assembled monolayer were less so, while those with the methyl-terminated one were the weakest.The investigators found that the AFM system offers mechanical manipulation with nanometer/nanonewton resolution and with high precision and control. For this reason, and because the system is so compact, it could contribute to a variety of applications in biotechnology; for example, cell manipulation and force detection.There also are some disadvantages. For example, Hierlemann said, the system’s spatial resolution restricts it to the study of larger molecules and, as a result, it is not suitable for many crystallographic problems. The limited resolution derives from the use of a piezoresistive rather than an optical readout mechanism and from the operation of the cantilever in constant-force mode.“Operating the cantilever in noncontact, resonant mode is expected to extend the resolution to the atomic domain,” Hafizovic said. “Implementing an integrated phase-lock loop for this application is the subject of current research.”The scientists are working to develop the system in other ways, so as to facilitate its application. In particular, they are seeking to improve the resolution, to establish more precise analog-to-digital conversion, and to reduce the size of the circuitry and the chip. Moreover, besides developing a noncontact mode of operation, they are exploring tapping-mode operation.