Micron-sized Sensors Research Articles

High-Density Redox Amplified Coulostatic Discharge-Based Biosensor Array.

High-density biosensor arrays are essential for many cutting-edge biomedical applications including point-of-care vaccination screening to detect multiple highly-contagious diseases. Typical electrochemical biosensing techniques are based on the measurement of sub-pA currents for micron-sized sensors requiring highly-sensitive readout circuits. Such circuits are often too complex to scale down for high-density arrays. In this paper, a high-density 4,096-pixel electrochemical biosensor array in 180 nm CMOS is presented. It uses a coulostatic discharge sensing technique and interdigitated electrode geometry to reduce both the complexity and size of the readout circuitry. Each biopixel contains an interdigitated microelectrode with a 13 aA low-leakage readout circuit directly underneath. Compared to standard planar electrodes, the implemented interdigitated electrodes achieve a maximum amplification factor of 10.5× from redox cycling. The array's sensor density is comparable to state-of-the-art arrays, all without augmenting the sensors with complex post-processing. The detection of anti-Rubella and anti-Mumps antibodies in human serum is demonstrated.

Uniform aligned bioconjugation of biomolecule motifs for integration within microfabricated microfluidic devices

Full details and a step-by-step guide suitable for printing proteins aligned to micron-sized sensors and subsequent integration and alignment of microfluidic structures are presented. The precise alignment and grafting of micron-sized biomolecule patterns with an underlying substrate at predefined locations is achieved using a novel semi-automated microcontact printer. Through integration of optical alignment methods in the x, y, and z directions, uniform contact of micron-sized stamps is achieved. Feature compression of the stamp is avoided by fine control of the stamp during contact. This printing method has been developed in combination with robust, compatible bioconjugate chemistry for patterning of a dextran-functionalized silicon oxide substrate with a NeutrAvidin-“inked” stamp and subsequent incubation with a biotin-functionalized protein. The bioconjugate chemistry is such that uniform coverage of the protein (without denaturation) over the printed motif is obtained and reproduction of the initial mask shape and dimensions is achieved. Later integration with a microfluidic structure aligned with the printed motif on the substrate is also described.

1 ∕ f noise in linearized low resistance MgO magnetic tunnel junctions

Low RA MgO magnetic tunnel junctions prepared at Singulus (Ta3∕CuN30∕Ta5∕PtMn20∕CoFe2.5∕Ru0.7∕CoFeB3∕MgO1.2∕CoFeB3∕Ta5 (thickness in nanometers) were microfabricated at INESC-MN. The junctions were patterned into micron-sized sensors (5–20μm2) with controlled shape anisotropy (aspect ratio ranging from 2 to 20). A small external longitudinal bias field (15–30 Oe) was further used to improve sensor linearity. The MgO junctions have a resistance-area product of 150Ωμm2 and a maximum tunnel magnetoresistance of 130%. Noise measurements were done in linearized sensors, from dc to 500 kHz. The magnetic and nonmagnetic contributions to the 1∕f noise were determined. From the data fitting, Hooge parameters of ∼2.20×10−9μm2 were obtained for the nonmagnetic 1∕f noise. Analysis of direct experimental data revealed the possibility to detect variations of magnetic fields in the order of 10−10T∕Hz0.5 with these MgO junctions, demonstrating their potential for ultralow-field detection.

Geometry optimization of TMR current sensors for on-chip IC testing

It was demonstrated that submicron and micron-sized tunnel magnetoresistive sensors having similar structure as magnetic random access memories can be used as very sensitive current sensors in /spl mu/A-mA ranges, with a resolution of 5 /spl mu/A. A number of variations in aspect ratio and dimensions, ranging from submicron to several microns, have been included in the design in order to investigate the influence of the sensor geometry on sensor properties. The influence of the shape anisotropy on the sensitivity is dominant over the current line width. Hysteresis investigations revealed that hysteresis of micron-sized sensors remains low and does not change significantly with the aspect ratio, while hysteresis of sensors with <2 /spl mu/m rises drastically with decreasing shape anisotropy, especially aspect ratios close to 1. Invesigations of the temperature rise due to the Joule heating effect caused by the current under test also suggests that sensors of submicron size should be avoided to minimize sensitivity changes caused by the current heating effect.

Correlated Oscillations in Glucose Consumption, Oxygen Consumption, and Intracellular Free Ca2+ in Single Islets of Langerhans

Micron-sized sensors were used to monitor glucose and oxygen levels in the extracellular space of single islets of Langerhans in real-time. At 10 mM glucose, oscillations in intraislet glucose concentration were readily detected. Changes in glucose level correspond to changes in glucose consumption by glycolysis balanced by mass transport into the islet. Oscillations had a period of 3.1 +/- 0.2 min and amplitude of 0.8 +/- 0.1 mM glucose (n = 21). Superimposed on these oscillations were faster fluctuations in glucose level during the periods of low glucose consumption. Oxygen level oscillations that were out of phase with the glucose oscillations were also detected. Oscillations in both oxygen and glucose consumption were strongly dependent upon extracellular Ca(2+) and sensitive to nifedipine. Simultaneous measurements of glucose with intracellular Ca(2+) ([Ca(2+)](i)) revealed that decreases in [Ca(2+)](i) preceded increases in glucose consumption by 7.4 +/- 2.1 s during an oscillation (n = 9). Conversely, increases in [Ca(2+)](i) preceded increases in oxygen consumption by 1.5 +/- 0.2 s (n = 4). These results suggest that during oscillations, bursts of glycolysis begin after Ca(2+) has stopped entering the cell. Glycolysis stimulates further Ca(2+) entry, which in turn stimulates increases in respiration. The data during oscillation are in contrast to the time course of events during initial exposure to glucose. Under these conditions, a burst of oxygen consumption precedes the initial rise in [Ca(2+)](i). A model to explain these results is described.

MICRO-ELECTRO-MECHANICAL-SYSTEMS (MEMS) AND FLUID FLOWS

▪ Abstract The micromachining technology that emerged in the late 1980s can provide micron-sized sensors and actuators. These micro transducers are able to be integrated with signal conditioning and processing circuitry to form micro-electro-mechanical-systems (MEMS) that can perform real-time distributed control. This capability opens up a new territory for flow control research. On the other hand, surface effects dominate the fluid flowing through these miniature mechanical devices because of the large surface-to-volume ratio in micron-scale configurations. We need to reexamine the surface forces in the momentum equation. Owing to their smallness, gas flows experience large Knudsen numbers, and therefore boundary conditions need to be modified. Besides being an enabling technology, MEMS also provide many challenges for fundamental flow-science research.