Biochip fabricated with micro-electronic technology has become a new powerful tool in molecular biology. In particular, high-density deoxyribonucleic acid (DNA) micro-array can significantly reduce cost and time to perform complicated clinical diagnosis like DNA mutations responsible for some genetic diseases (such as cancers) and DNA sequence analysis for virus detection. Currently, the most well developed DNA detection methodology is based on the modification of DNA sample with fluorescent labels so that DNA matched with a particular probe immobilized at a specific location of a solid support (e.g. glass slides) can be identified by the optical emission from the fluorescence label. However, this method has some limitations such as: requirement of some expensive optical instruments to...[ Read more ]

Biochip fabricated with micro-electronic technology has become a new powerful tool in molecular biology. In particular, high-density deoxyribonucleic acid (DNA) micro-array can significantly reduce cost and time to perform complicated clinical diagnosis like DNA mutations responsible for some genetic diseases (such as cancers) and DNA sequence analysis for virus detection. Currently, the most well developed DNA detection methodology is based on the modification of DNA sample with fluorescent labels so that DNA matched with a particular probe immobilized at a specific location of a solid support (e.g. glass slides) can be identified by the optical emission from the fluorescence label. However, this method has some limitations such as: requirement of some expensive optical instruments to excite the fluorescent labels and to capture the output of the fluorescence and unreliability of signal intensity (caused by the fluorescence quench).

Besides fluorescent label, nano-metallic particle can also be used as labels. Compared with the fluorescence-based detection method, the advantages of nanoparticle based DNA detection method lead to more consistent experimental results. Previous work using the conducting property of the metal particle has been proposed but it requires modifications to the CMOS process to include inert metal and different surface passivation techniques, making it more difficult to be fabricated in ordinary IC foundries.

In this work, various strategies have been investigated to develop gold nanoparticle based DNA chip, which is fully compatible with the standard CMOS process while still feature high detection sensitivity and selectivity.

A CMOS-array-based DNA chip is demonstrated. Detection transistor can be turned on when a silver conductive bridge forms between the gaps at the location with perfect matched DNA sample. The difference of the output of negative control, matched and mismatched DNA is sufficient for distinguish. The relationship between the sensitivity and silver enhancement time is studied; showing the sensitivity of the system can be enhanced by using longer silver deposition time. And a low concentration of 1pM can be detected.

A CMOS image sensor based DNA chip is also demonstrated. The transduction from hybridization results to electronic signal and its selectivity, sensitivity is studied. This chip is based on integrated APS to detect the signal change in opacity when an opaque nano-particle is deposited at the location with perfectly matched DNA samples. The DNA chip is fabricated with a standard 0.5 μm CMOS process. The optical property of the deposited nanoparticles has been carefully studied and calibrated indicating a difference can be measured under most optical spectrum in the visible light region. The sensitivity has also been tested of low concentration detection. It is reasonable that this technology can also be applied to low micron or nanometer size spots by making use of the advanced modern IC manufacturing technology.