Abstract
A compact integrated system-on-chip (SoC) architecture solution for robust, real-time, and on-site genetic analysis has been proposed. This microsystem solution is noise-tolerable and suitable for analyzing the weak fluorescence patterns from a PCR prepared dual-labeled DNA microchip assay. In the architecture, a preceding VLSI differential logarithm microchip is designed for effectively computing the logarithm of the normalized input fluorescence signals. A posterior VLSI artificial neural network (ANN) processor chip is used for analyzing the processed signals from the differential logarithm stage. A single-channel logarithmic circuit was fabricated and characterized. A prototype ANN chip with unsupervised winner-take-all (WTA) function was designed, fabricated, and tested. An ANN learning algorithm using a novel sigmoid-logarithmic transfer function based on the supervised backpropagation (BP) algorithm is proposed for robustly recognizing low-intensity patterns. Our results show that the trained new ANN can recognize low-fluorescence patterns better than an ANN using the conventional sigmoid function.
Highlights
The development of low-cost portable instruments for rapidly analyzing genetic assays would significantly advance the level of medical services globally
The polymerase chain reaction (PCR) amplification and the capillary electrophoretic (CE) techniques are often adopted for genetic analysis
By taking advantages of the VLSI microfabrication technologies and artificial neural network theories, we proposed a microsystem consisting of a unique optical configuration setup, a differential logarithm sensorprocessor array chip, and an ANN SoC processor chip for fast recognizing and analyzing the PCR prepared genetic patterns
Summary
The development of low-cost portable instruments for rapidly analyzing genetic assays would significantly advance the level of medical services globally. A real lowcost (∼10US$) pocket-sized PCR thermocycling device has been developed based on a smart technique of simultaneously pseudoisothermally heating multiple zones of a loop channel for PCR amplification [2] This thermocycler does not contain the CE separation, the fluorescence detection, and the data analysis functions. The integration of PCR and electrochemical (EC) transduction functionality on microfabricated silicon/glass-based devices for DNA amplification and detection was shown successfully [3] Their microfabricated device needs to operate with external control and data-acquisition systems. Regarding the goal of building a real compact PCR analysis system that can rapidly find and analyze the desired genetic patterns, the existing data acquisition and analysis systems (e.g., portable computers and interfaces) are considered relatively large in size and heavy in weight. In conjunction with the natural capabilities of an ANN listed above, a signal amplification stage that can augment the lowfluorescence input before the ANN stage would help the ANN to acquire data more reliably, and result in a more robust data analysis capability of the entire system
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