A CMOS/Thin-Film Fluorescence Contact Imaging Microsystem for DNA Analysis

Abstract

A hybrid CMOS/thin-film microsystem for fluorescence contact imaging is presented. The microsystem integrates a high-performance optical interference filter and a 128 128 pixel active pixel sensor fabricated in a standard 0.35-m CMOS technology. The thin-film filter has an optical density greater than 6.0 at the wavelength of interest, providing adequate excitation rejection to the 532-nm solid-state laser. Microsystem performance is experimentally validated by imaging spots of Cyanine-3 fluorophore, conventionally used in DNA detection. The emission intensity as a function of fluorophore concentration is measured with an estimated sensitivity of 5000 fluorophore m 2 . A human DNA microarray has been imaged with the sensor prototype.

CMOS Photodetectors

“…The low-cost polymer based filters is best suited for LED excitation and may not be able to provide optimum excitation rejection performance when laser radiation is used for excitation. As a more traditional alternative, Singh et al [111] proposed micromachining a commercially available thin-film interference filter and gluing it to the CMOS imager die. …”

VLSI-enabled DNA sequencing arrays

“…To count the incident photons, the generated photo-charge is integrated on capacitors utilizing either the direct integration techniques [8][9] or capacitive trans-impedance amplifiers (CTIA) [10][11]. Both these approaches can provide very high gain (> lOl2y / Asec) and can be designed to reach the fundamental shot-noise limit.…”

“…The excitation light typically has orders of magnitude higher photon flux than the generated signal which is at a higher wavelength (few tens of nm apart). It is therefore imperative to filter the excitation light utilizing optical filters [8] prior to reaching the transducer or use extremely high dynamic range photo-detectors. In practice, a combination of both is generally used.…”

“…Die photo of a bioluminescence-based SBS chip [II]. generally referred to as Pyrosequencing [8]. The imager detects the optical signal originating from the bead array placed on top of the chip.…”

CMOS Tunable-Wavelength Multi-Color Photogate Sensor

“…In particular, laser-induced fluorescence is a prominent sensory method for lab-on-a-chip devices [2]. Several groups have focused on the development of integrated fluorescence-based sensing platforms for applications ranging from cancer research [3], [4] to nucleic acid detection [1], [5].…”