Skip to main content
Premium Trial:

Request an Annual Quote

Formerly Twistnostics, Scanogen Looks to Develop First MDx Test for TB


NEW YORK (GenomeWeb) – MDx startup Twistnostics has renamed itself Scanogen and shifted its business status as it works to develop its first commercial product based on its proprietary molecular detection platform.

Scanogen CEO Alfredo Celedon told GenomeWeb this week that important technological advancements over the last year have brought the firm to the point where it is now seeking investment and partnerships to advance the product, a tuberculosis diagnostic.

Scanogen's initial core technology was the Twist-Biosensor, a single-molecule sensor that relies on DNA supercoiling to convert the nucleic acid hybridization of a target nucleic acid into a mechanical signal that can be detected using standard semiconductors. As the bound targets are subjected to disrupting torsional stress, the rate of detection is increased and background noise is reduced.

More recently, the firm has tackled another crucial step in optimizing its biosensors for use in pathogen detection or potentially cancer diagnosis, a technique the company calls Single Molecule Scanning.

Celedon told GenomeWeb that Scanogen spent the last year developing and testing SM-Scanning, which involves detecting the binding of target molecules to single-molecule biosensors within a capillary system.

"When you use a single-molecule biosensor, the sensor releases a signal when it binds to a target molecule. The problem is that the time it takes for a target — especially targets at low concentration — to find the sensor can [take] days or even weeks," Celedon explained.

"With a very small number of targets and sensors the process will be slow, so all the beauty of single-molecule detection is lost because even if you can detect a single molecule in solution you might have to wait weeks for it to bind to the sensor," he said.

One immediate way of solving that problem is to vastly increase the number of sensors used, which increases the probability of any single target finding a sensor, even at very low concentrations.

But, Celedon said, this raises another problem. "If you have a million or several million more sensors, which is the number you need to make this work, as we want, in a few minutes? How do you track that very large number of sensors?  You need a way of scanning them. That's what SM-Scanning is allowing us to do, to analyze millions of sensors in a short period of time."

Though he declined to discuss the technical details of the method, Celedon said that it involves detecting targets binding to sensors via micron-scale particles associated with each sensor.

The company has completed a number of experiments with SM-Scanning over the past year aimed at better understanding the analytical sensitivity of the system and improving and optimizing it.

Initially, Scanogen performed spiking experiments using synthetic oligonucleotides. "We spike a buffer solution with an oligonucleotide that has a target sequence we want to detect. Then we add our biosensors to that sample and we flow the mixture into the capillary and we image the capillary and analyze the images. Based on this, we calculate or infer how many biosensors bound to the target," Celedon explained.

In these experiments, Scanogen has found that it can detect target molecules at a one-femtomolar concentration.

"We haven't done below one fM, so we haven't studied carefully yet the limit of detection, but we know that one fM is detectable," Celedon said.

Similarly, using samples of tuberculosis cells spiked at different concentrations in solution, the company has found that it could successfully detect the presence of TB at 50 colony-forming units per ml without PCR amplification.

With these results in hand, the company is now moving on to develop commercial diagnostic devices using SM-Scanning. A central next step will be fully automating the process, which Scanogen expects to take about a year and half.

According to Celedon, the company's core technology is fairly simple and further developing it into an automated product should not be difficult. For testing of biological samples, there are several sample-preparation steps that the company is now investigating to identify the most cost-effective and efficient tools to automate and integrate into its SM-Scanning workflow.

"Our philosophy as a company is that biomolecules, in particular nucleic acids, should be [detectable] in a very simple process," Celedon said. "Currently most detection techniques use PCR. The problem is that this involves relatively expensive amplification systems and reagents. In our case, the only reagents are DNA molecules and beads. The apparatus is simple too. There is no temperature cycling — only an incubation step that takes place at a constant temperature. And then imaging does not require a microscope."

Scanogen has several ongoing research projects evaluating its technology for various applications, including infectious disease diagnosis, early cancer detection, and the detection of pathogen drug resistance.

The company expects its tuberculosis test to be first to market, and is looking for partnerships and funding in this vein.

The test is intended to be implemented in small labs or medical centers in the developing world, as close as possible to the point-of-care, where sputum microscopy — which has notoriously low sensitivity — is still widely used for TB diagnosis.

This is changing with the introduction of PCR-based TB tests such as Cepheid's Xpert MTB/RIF assay, but, based on its early experiments, Scanogen believes it can meet or exceed PCR's detection limit. Cepheid's test, for instance, has a limit of detection of about 130 CFU/ml, although Cepheid is already developing a next-generation test that aims to bring that down to about 10 CFU/ml.

Celedon also said that the reduced complexity and costs of the SM-Scanning approach would also be an advantage over PCR. Scanogen's goal is to sell its device for $2,000 with each test costing less than $8.