IEDM PREVIEW, PART II
by Phil LoPiccolo, Editor-in-Chief
At the International Electron Devices Meeting (IEDM) this December 11-13 in San Francisco, researchers will demonstrate that just as biological processes are being pursued to augment semiconductor device fabrication (see Part 1 of this IEDM bioelectronics preview), so too are the products of such techniques poised to advance biological and medical research.
A prime example of this trend, presented in a paper by a team at the U. of Illinois, describes how nanoscale “pores” in ultrathin SOI-based membrane capacitors can be used for real-time sequencing of DNA molecules. The concept takes advantage of the fact that individual base-pairs of DNA molecules have different dipole moments that can create unique voltage changes as they pass through the pores. Biologists can therefore assign these electrical signatures to identify specific genes.
The researchers fabricated the “nanopore gene detector” by depositing a gate oxide and polysilicon layer onto a thinned SOI substrate. After etching the substrate, they used a tightly focused e-beam to produce nanopores with radii as small as 0.34nm in a capacitor membrane less than 40nm thick. When the membrane is immersed in an electrolyte and a voltage is applied, an ion current develops through the pores. As DNA, which is a polyanion, is injected at the negative electrode, it is drawn across the membrane through the pore. To identify the DNA molecules, the researchers measured voltage changes at electrode collars positioned around the pores. The high spatial and temporal resolution of the nanopore technology could used to improve DNA data acquisition and analysis.
A Stanford group has taken a different approach to DNA analysis by building a “magnetic biochip” containing giant magnetoresistive (GMR) spin-valve sensor arrays (see photo, above). Using the GMR approach, the researchers are able to identify specific DNA sequences by reading the electrical signal variations that occur when biomaterials labeled with magnetic nanotags are subjected to changes in applied magnetic fields modulated at a predetermined frequency.
To capture the DNA sequences they wished to analyze, the researchers coated single-strand DNA “probes” on the sensor array that binds to DNA structures containing those sequences. The captured DNA structures, called “targets,” are then labeled with nanotags. The nanotags landing on sensors lead to changes in the surrounding magnetic field, which are then converted into a unique electrical signature identifying each sequence captured on a given sensor. The sensor array contains more than 1000 sensing elements within a 1mm2 area and is integrated with 0.25µm BiCMOS circuitry on a chip. If different DNA probes are immoblized on different sensors, then the relative abundance of many different DNA targets in a sample can be analyzed simultaneously in one test by reading out electrical signals of the entire sensor array (called “multiplex assay” in biology).
The researchers claim that systems based on GMR sensor arrays may soon rival or exceed more complex and expensive optical detection techniques based on the recognition of surface-bonding fluorescent tags, and may make low-cost portable diagnostic instruments feasible.
Whereas the U. of Illinois and Stanford work deals with detecting and identifying unknown DNA strands, a new technique developed by CombiMatrix enables the synthesis of DNA on a CMOS chip. The chip consists of an active electrode array optimized for biochemical applications, with a platinum overlay, local memory, and up to 94,928 electrodes (see image, below). The chip is coated with a proprietary membrane containing free hydroxyl groups — the starting point for the synthesis of DNA structures. As synthesis proceeds, an acid that is typically introduced naturally to control a key reaction step is instead produced electrochemically on the chip at designated electrodes. Overall synthesis optimization is determined by the current and voltage settings as well as the reagents present. The researchers contend that on-chip DNA synthesis could be used for a host of applications, including drug research, protein and pathogen screening, drug research, peptide synthesis, and DNA diagnostics. — P.L.
Photo above: Magnetic biochip (courtesy of Stanford)
Photo below: On-chip DNA synthesis (courtesy of CombiMatrix)