Terunobu Akiyama

Assessment of insulated conductive cantilevers for biology and electrochemistry

This paper describes the characterization and application of electrically insulated conductive tips mounted on a cantilever for use in an atomic force microscope and operated in liquid. These multifunctional probes were microfabricated and designed for measurements on biological samples in buffer solution, but they can also be employed for electrochemical applications, in particular scanning electrochemical microscopy. The silicon nitride based cantilevers had a spring constant ≤0.1 N m-1 and a conductive tip, which was insulated except at the apex. The conductive core of the tip consisted of a metal, e.g. platinum silicide, and exhibited a typical radius of 15 nm. The mechanical and electrical characterization of the probe is presented and discussed. First measurements on the hexagonally packed intermediate layer of Deinococcus radiodurans demonstrated the possibility to adjust the image contrast by applying a voltage between a support and the conductive tip and to measure variations of less than 1 pA in faradaic current with a lateral resolution of 7.8 nm.

Symmetrically arranged quartz tuning fork with soft cantilever for intermittent contact mode atomic force microscopy

A self-sensing and -actuating probe for dynamic mode atomic force microscopy (AFM) based on a commercial quartz tuning fork and a microfabricated cantilever is presented. The U-shaped cantilever, exhibiting a sharp tip, is combined with the tuning fork in a symmetrical arrangement, such that each of the two legs of the cantilever is fixed to one of the prongs of the tuning fork. The tuning fork is used as an oscillatory force sensor. Its frequency and amplitude govern that of the tip vibration, while the cantilever determines the spring constant of the whole probe. The frequency of the tip vibration for AFM operations can be much higher than the resonance frequency of the cantilever. A probe comprising a silicon nitride cantilever (0.1 N/m) is used to image monoatomic terraces of graphite in the intermittent contact mode. A much softer cantilever (0.01 N/m) is used to analyze the topography of a microelectronic chip in the same mode. Moreover, a bacterial surface layer hexagonally packed intermediate layer of Deinococcus radiodurans is imaged in a buffer solution. The tip vibration was again generated by the tuning fork while the sample interaction was measured using the standard optical detection scheme in this experiment. These probes are suited for batch fabrication and assembly and, therefore, enlarge the applications for the tuning fork based AFM.

Sub-ppm detection of vapors using piezoresistive microcantilever array sensors

The performance of microfabricated piezoresistive cantilever array sensors has been evaluated using various vapors of volatile organic compounds including alkanes with different chain length from 5 (n-pentane) to 14 (n-tetradecane). We demonstrate that piezoresistive microcantilever array sensors have the selectivity of discriminating individual alkanes in a homologous series as well as common volatile organic compounds according to principal component analysis. We developed a new method to evaluate the sensitivity, taking advantage of the low vapor pressures of alkanes with longer chains, such as n-dodecane, n-tridecane and n-tetradecane, under saturated vapor conditions. This method reveals sub-ppm sensitivity and the cantilever response is found to follow the mass of evaporated analytes as calculated using a quantitative model based on the Langmuir evaporation model.

Development of Insulated Conductive Probes with Platinum Silicide Tips for Atomic Force Microscopy in Cell Biology

A microfabrication process of a multifunctional probe is introduced for atomic force microscopy and various electrochemical measurements on biological samples in buffer solution. The silicon nitride probes have a spring constant lower than 0.1 N/m and a conductive tip, which is tightly insulated except at the apex. The conductive core of the tip consists of PtxSi y and shows a typical radius of curvature of 15 nm. A simultaneous measurement of topography and electrical current on graphite in air was demonstrated.

Advanced temperature compensation for piezoresistive sensors based on crystallographic orientation

We describe a highly effective method of reducing thermal sensitivity in piezoresistive sensors, in particular silicon cantilevers, by taking advantage of the dependence of the piezoresistive coefficient of silicon on crystallographic orientation. Two similar strain-sensing elements are used, positioned at 45 degrees to each other: One is set along a crystalline axis associated with a maximum piezoresistive coefficient to produce the displacement signal, while the other is set along an axis of the vanishing coefficient to produce the reference signal. Unlike other approaches, both sensing elements are coupled to the same cantilever body, maximizing thermal equilibration. Measurements show at least one order of magnitude improvement in thermal disturbance rejection over conventional approaches using uncoupled resistors.

Two dimensional array of piezoresistive nanomechanical Membrane-type Surface Stress Sensor (MSS) with improved sensitivity.

We present a new generation of piezoresistive nanomechanical Membrane-type Surface stress Sensor(MSS) chips, which consist of a two dimensional array of MSS on a single chip. The implementation of several optimization techniques in the design and microfabrication improved the piezoresistive sensitivity by 3∼4 times compared to the first generation MSS chip, resulting in a sensitivity about ∼100 times better than a standard cantilever-type sensor and a few times better than optical read-out methods in terms of experimental signal-to-noise ratio. Since the integrated piezoresistive read-out of the MSS can meet practical requirements, such as compactness and not requiring bulky and expensive peripheral devices, the MSS is a promising transducer for nanomechanical sensing in the rapidly growing application fields in medicine, biology, security, and the environment. Specifically, its system compactness due to the integrated piezoresistive sensing makes the MSS concept attractive for the instruments used in mobile applications. In addition, the MSS can operate in opaque liquids, such as blood, where optical read-out techniques cannot be applied.

Characterization of an integrated force sensor based on a MOS transistor for applications in scanning force microscopy

In this article an integrated force sensor based on a stress-sensing MOS transistor is introduced for applications in scanning force microscopy (SFM) . The sensor configuration will be described, and theoretical and experimental investigations of the sensitivity will be presented. With the fabrication process, consisting of a standard CMOS process and post-processing (conventional silicon bulk micromachining), cantilevers with MOS transistors integrated at the base for deflection detection have been fabricated. The cantilevers typically have a spring constant of 1 N m-1, are 400 to 950 um in length and have a mechanical resonance frequency between 6.2 and 35 kHz. It is found that the stress sensitivity of the MOS transistor changes with the gate voltage, while being independent of the drain voltage. The cantilevers have successfully been used for SFM imaging in both contact mode and dynamic mode (tapping mode). These cantilevers together with integrated circuits are expected to be well suited for mass production because of their CMOS processing compatibility.

Development of Atomic Force Microscope for Arthroscopic Knee Cartilage Inspection

A recent study, based on ex vivo unconfined compression testing of normal, diseased, and enzymatically altered cartilage, revealed that a scanning force microscope (SFM), used as a nano-intender, is sensitive enough to enable measurement of alterations in the biomechanical properties of cartilage. Based on these ex vivo measurements, we have designed a quantitative diagnosis tool, the scanning force arthroscope (SFA), able to perform in vivo measurements during a standard arthroscopic procedure. For stabilizing and positioning the instrument relative to the surface under investigation, a pneumatic system has been developed. A segmented piezoelectric tube was used to perform the indentation displacement, and a pyramidal nanometer-scale silicon tip mounted on a cantilever with an integrated deflection sensor measured the biomechanical properties of cartilage. Mechanical means were designed to protect the fragile cantilever during the insertion of the instrument into the knee joint. The stability of the pneumatic stage was checked with a prototype SFA. In a series of tests, load-displacement curves were recorded in a knee phantom and, more recently, in a pigs leg.

Double-Side-Coated Nanomechanical Membrane-Type Surface Stress Sensor (MSS) for One-Chip-One-Channel Setup

With their capability for real-time and label-free detection of targets ranging from gases to biological molecules, nanomechanical sensors are expected to contribute to various fields, such as medicine, security, and environmental science. For practical applications, one of the major issues of nanomechanical sensors is the difficulty of coating receptor layers on their surfaces to which target molecules adsorb or react. To have measurable deflection, a single-side coating is commonly applied to cantilever-type geometry, and it requires specific methods or protocols, such as inkjet spotting or gold-thiol chemistry. If we can apply a double-side coating to nanomechanical sensors, it allows almost any kind of coating technique including dip coating methods, making nanomechanical sensors more useful with better user experiences. Here we address the feasibility of the double-side coating on nanomechanical sensors demonstrated by a membrane-type surface stress sensor (MSS) and verify its working principle by both finite element analysis (FEA) and experiments. In addition, simple hand-operated dip coating is demonstrated as a proof of concept, achieving practical receptor layers without any complex instrumentation. Because the double-side coating is compatible with batch protocols such as dip coating, double-side-coated MSS represents a new paradigm of one-chip-one-channel (channels on a chip are all coated with the same receptor layers) shifting from the conventional one-chip-multiple-channel (channels on a chip are coated with different receptor layers) paradigm.

In situ measurements of human articular cartilage stiffness by means of a scanning force microscope

Osteoarthritis is a painful and disabling progressive joint disease, characterized by degradation of articular cartilage. In order to study this disease at early stages, we have miniaturized and integrated a complete scanning force microscope into a standard arthroscopic device fitting through a standard orthopedic canula. This instrument will allow orthopedic surgeons to measure the mechanical properties of articular cartilage at the nanometer and micrometer scale in-vivo during a standard arthroscopy. An orthopedic surgeon assessed the handling of the instrument. First measurements of the elasticity-modulus of human cartilage were recorded in a cadaver knee non minimal invasive. Second, minimally invasive experiments were performed using arthroscopic instruments. Load-displacement curves were successfully recorded.