We report the selective and real-time detection of label-free DNA using an electronic readout. Microfabricated silicon field-effect sensors were used to directly monitor the increase in surface charge when DNA hybridizes on the sensor surface. The electrostatic immobilization of probe DNA on a positively charged poly-L-lysine layer allows hybridization at low ionic strength where field-effect sensing is most sensitive. Nanomolar DNA concentrations can be detected within minutes, and a single base mismatch within 12-mer oligonucleotides can be distinguished by using a differential detection technique with two sensors in parallel. The sensors were fabricated by standard silicon microtechnology and show promise for future electronic DNA arrays and rapid characterization of nucleic acid samples. This approach demonstrates the most direct and simple translation of genetic information to microelectronics. Awide range of techniques for detecting nucleic acids is based on their hybridization to DNA probes on a solid surface (ref. 1, entire issue, and ref. 2). In the methods used most routinely, the physical nature of the readout requires the attachment of reporter molecules such as fluorescent, chemiluminescent, redox, or radioactive labels (1, 3, 4). Although labeldependent methods achieve the highest sensitivities (5-7), eliminating the labeling steps has the advantage of simplifying the readout and increasing the speed and ease of nucleic acid assays, which is especially desirable for characterizing infectious agents, scoring sequence polymorphisms and genotypes, and measuring mRNA levels during expression profiling. The development of label-independent methods that can monitor hybridization in real time and that are simple and scalable is still in its infancy (8-11). Here we describe a label-free method for electronically detecting DNA by its intrinsic molecular charge using microfabricated field-effect sensors.The field-effect sensor is based on an electrolyte-insulator-silicon (EIS) structure. Variations in the insulator-electrolyte surface potential, which arise from the binding of charged molecules (e.g., nucleic acids) to the insulator surface ( Fig. 1 a and b), modify the charge distribution in the silicon below the electrolyte. Surface charge and surface potential at this interface are related according to the Grahame equation (12). The surface potential can be measured by changes in conductivity (13) or capacitance (14) in the silicon part of the EIS structure. We have chosen to measure the capacitance, because it requires only one electrical connection to the silicon. The measured capacitance between the silicon and counter electrode in the electrolyte solution is dominated by the insulator capacitance and the capacitance of the charge-depleted region in the silicon. These two capacitances appear in series, and only the silicon depletion capacitance is modulated by the insulator surface potential. The capacitance-versus-voltage dependence of EIS structures (15) is similar to that of metal-oxide-semiconducto...
An areal density of 1.6 Tbits/in. 2 has been achieved by anodically oxidizing titanium with the atomic force microscope ͑AFM͒. This density was made possible by ͑1͒ single-wall carbon nanotubes selectively grown on an AFM cantilever, ͑2͒ atomically flat titanium surfaces on ␣-Al 2 O 3 ͑1012͒, and ͑3͒ atomic scale force and position control with the tapping-mode AFM. By combining these elements, 8 nm bits on 20 nm pitch are written at a rate of 5 kbit/s at room temperature in air.
We demonstrate a promising type of microfabricated accelerometer that is based on the optical interferometer. The interferometer consists of surface-micromachined interdigital fingers that are alternately attached to a proof mass and support substrate. Illuminating the fingers with coherent light generates a series of diffracted optical beams. Subangstrom displacements between the proof mass and frame are detected by measuring the intensity of a diffracted beam. The structure is fabricated with a two-mask silicon process and detected with a standard laser diode and photodetector. We estimate that the minimum detectable acceleration is six orders of magnitude below the acceleration of gravity, i.e., 2 μg/Hz in a 1 Hz bandwidth centered at 650 Hz.
We show that a microfabricated field-effect sensor located at the terminus of a freestanding cantilever can detect surface potential changes resulting from the adsorption of charged molecules in an aqueous environment. The charge sensitive region, defined by lightly doped silicon, is embedded within the heavily doped silicon cantilever. Since both the electrical trace and sensitive region are passivated with thermally diffused silicon dioxide, the entire cantilever can be immersed in buffer solutions and cleaned with strong acids without degrading its electrical response. As an example, we demonstrate that the device can reproducibly detect adsorption of positively charged poly-L-lysine (PLL) on silicon dioxide. We also demonstrate that PLL adsorption and pH can be measured in discrete solutions by scanning the cantilever through parallel, distinct streams within a microfluidic channel array.
A pH sensitive scanning probe is realized by integrating a micron-sized field-effect sensor onto a cantilever designed for an atomic force microscope. The hybrid device, called a scanning probe potentiometer (SPP), is capable of measuring pH gradients over a sample surface. The device was used to profile the pH across a reservoir of laminar streams created by fluid flow in an array of microfluidic channels of varying pH. When a single SPP scanned, a 1.5 mm reservoir in a 10-channel array, the pH profile was measured in less than 1 min with a spatial resolution of 10 μm and sensitivity of less than 0.01 pH units.
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