Introducing Digital Biology

Quantum Logic Devices has created a paradigm-shifting technology that provides a better way to study biomolecular interactions, akin to the leap from vacuum tubes to transistor integrated circuits. Single molecules can be studied in real time without the overhead of optical technologies, while retaining the power of the microarray format.

Based on ultra-sensitive single electron transistors (SETs), this new platform heralds the convergence of silicon microelectronics with biology. This interface of the ‘wet” and “dry” sides of nanotechnology produces exciting synergies that enhance the quality and significance of the data by eliminating the background noise associated with fluorescent labels.

 

Simplify Your Assay - Eliminate Costly Steps

Fluorescent microarrays require attachment of dye molecules to DNA targets to determine their adsorption onto matching DNA probe spot on the array.

Optical detector sensitivity thresholds require large numbers of labeled targets be present for detection. For low-abundance genes, this requires chemical amplification by polymerase chain reaction (PCR) or other technique.

Target hybridization to the probes is accomplished under low-stringency conditions favoring adsorption of large amounts of material, followed by wash steps to remove unbound molecules.

Besides being tedious and time consuming, each of these steps introduces error into the final result. Post-processing discards the top and bottom 10% of data to correct for this error. Additionally, variable label incorporation efficiencies demand calibration prior to each experiment.

On the other hand, QLD's SET offers a direct, label-free, electronic method for hybridization detection. Therefore, the SET operates under high stringency conditions favoring only perfect probe and target matches. Direct electronic detection does not require target labeling or chemical enhancement. Furthermore, single molecule detection capability eliminates the need for target amplification.

Therefore, the SET affords a simpler, faster, and more reliable test protocol as illustrated in the figure.

Eliminate the Noise

Optical labels, wash steps and other complex chemistries add to background noise in fluorescent assays. Optical methods are susceptible to background light and interference due to variations in substrates and fluorescent labels.A significant portion of data is discarded to remove background noise prior to interpretation of results.

The fluorescent labels used have less than perfect incorporation into the target molecules, therefore, some targets may not be detected. Additionally, non-specific binding between labels and the substrate or other molecules in the sample skews results.

QLD's SET technology eliminates this background noise, improving the accuracy of hybridization data. The SET is a direct, electronic detection method operating at the single molecule level. Therefore, none of the complex chemistries and processes associated with amplification or attachment of optical labels is required.

Each SET, corresponding to a single molecular probe/target interaction is independently addressable, enabling detection of even low copies of target. Removal of optical detection from the process also removes optical scattering as a source of noise.

The SET Advantage
• SET Technology Overview
• SET Basics
 
 
 

Reproducible and Reliable

Optical labels reduce target-probe binding efficiency and specificity reducing result consistency between experiments. Additionally, variations in silicon or glass substrates randomly scatter light; hence further reducing repeatability between experiments.

Over their lifetime, light sources and detectors vary in intensity and sensitivity, respectively, requiring routine calibration. Furthermore, users perceive the intensity and color of each fluorescent spot differently. This subjective interpretation of the same result adds to variation between tests.

Variability between experiments inhibits comparison between two slides or between spots on the same slide.

The SET platform provides a more reliable and consistent platform upon which to explore molecular interactions. Because the SET is a solid-state device, built using conventional CMOS processes, each transistor functions identically to all others on the array. Conventional spotting methods verify probe activity prior immobilization on the array, ensuring results match the biological question of interest.

The SET detection method removes subjective interpretation and background noise. The SET's electronic signal is a direct indication the probe target binding reaction. Furthermore, there is no background noise from non-specific binding to the silicon substrate, affording meaningful comparison across and between arrays.

QLD's SET technology is self normalizing, accounting for any slight variation in fabrication between test sites. Additionally, QLD has proprietary real time data analysis methods accounting for minor variations in particle and probe size without discarding data.