Methodology

A novel technology developed by DestiNA Genomics (DGL© technology) is based on combining its patented aldehyde modified SMART Nucleobases with unique peptide nucleic acid (PNA) capture probes that have been synthesised with a ‘blank’ position (DGL probes). DGL technology applies "dynamic chemistry" to DGL probes for the development of an entirely novel chemical, rather than enzymatic, method for nucleic acid testing. A correct detection signal can ONLY be achieved if:

  • a) The target nucleic acid sequence binds in perfect alignment to DGL probe;
  • b) The correct SMART Nucleobase seats into the ‘blank’ position formed by the duplex AND;
  • c) The SMART Nucleobase is "locked-in" chemically.

If mis-alignments between the target nucleic acid and DGL probe, or random attachments of the target nucleic acid to array/bead surfaces occur (a recurrent problem with enzyme based detection systems), DGL chemistry does not detect this, hence NO "false positives" can be recorded. DestiNA Genomics Ltd. (DGL) technology can be used to identify any known target nucleic acid sequence, including insertion and deletion mutations, as well as non-mutated nucleic acid sequences. This gives the DGL technology a unique, powerful position versus current detection methods.

DGL probes and SMART Nucleobases have already been adapted to be used on different diagnostic platforms. Three of the most common diagnostic platforms in use today are: mass spectrometry, fluorescence and colorimetric systems. DGL technology is compatible with all of them.

Now DGL technology will be adapted to the acoustic sensing platform developed by AWSensors (con link a la web de AWSensors). It is based in a patented characterization method of acoustic sensors at high frequency but keeping the noise level low, thus providing higher sensitivity and lower limit of detection

Acoustic sensing has taken advantage of the progress made in the last decades in piezoelectric resonators for radio-frequency (RF) telecommunication technologies. The piezoelectric elements used in radars, cellular phones or electronic watches for the implementation of filters, oscillators, etc..., have been applied to sensors. The so-called gravimetric technique is based on the change in the resonance frequency experimented by the resonator due to a mass attached on the sensor surface; it has opened a great deal of applications in bio-chemical sensing in both gas and liquid media. Acoustic microsensor based techniques combine their direct detection, real-time monitoring, high sensitivity and selectivity capabilities with a reduced cost in relation to other techniques. Different types of acoustic sensing elements exist, varying in wave propagation and deflection type, and in the way they are excited. They can be classified into two categories: bulk acoustic waves (BAW) and surface-generated acoustic waves (SGAW). Moreover they may work with longitudinal waves (with the deflection in the direction of propagation) or shear waves (with the deflection perpendicular to the direction of propagation). The number of biochemical applications is extended for in-liquid applications; in these cases it is necessary to minimize the acoustic radiation into the medium of interest and the shear wave is mostly used.

Although acoustic techniques have been improved in terms of robustness and reliability and allow measuring molecular interactions in real time, the main challenges remain on the improvement of the sensitivity, multi-analysis and integration capabilities. High sensitivity is possible by working with high frequency acoustic wave microresonators. Furthermore, high fundamental acoustic sensors can be miniaturized more easily. This miniaturization capability makes possible the integration of sensors in an array configuration. Therefore, when high sensitivity and multi-analysis detection are simultaneously required a viable solution goes through a system based on High fundamental frequency acoustic wave microresonator array. Effectively, monolithic multichannel sensor on a single quartz substrate is considered a very promising technology because it leads to benefits including lower cost, less sample/reagent consumption, faster sensing response and shorter detection assay time. A new characterization technique, especially appropriate for characterizing shear-wave acoustic wave microresonators in biosensor application, where very small frequency shifts are expected, has been developed and patented by AWSensors. This characterization method has been successfully applied on acoustic wave microsensors up to 150MHz fundamental frequency and has a high integration capability, being especially applicable for the characterization of sensor array and avoiding most of the problems of oscillators.

It consists on electrically exciting the sensors at a fix frequency and measuring the phase and amplitude of the sensor ́s response. Changes in the acoustic wave properties due to the binding processes will be translated to changes in both electrical phase and amplitude-shifts. As it has been previously stated, the higher the sensor fundamental frequency is, the higher its sensitivity but also its noise are. Alternative characterization methods do not provide any appreciable improvement in LoD working at higher frequencies. However, AWSensors approach keeps the noise level low even for high frequencies, thus taking advantage the higher sensitivity and improving the limit of detection. Very high sensitive measurements have been recently reported with a LoD better than SPR with the same experimental protocol and the same analyte and receptor in a competitive assay by AWS acoustic wave technology.

Liqbiopsens approach aims to further develop a novel system for early diagnostic of CRC and robust monitoring of this disease using non invasive methods based on ‘liquid biopsy’ concept. Solution proposed by the Liqbiopsens project relies on the multidisciplinary integration of different Key Enabled Technologies: microelectronics, microfluidics, nanomaterials and genomics. In particular, Liqbiopsens platform is based on the integration of two novel complementary technologies. On the one hand, the revolutionary DGL© technology property of DestiNA Genomics Ltd, capable of delivering faster, more error-free detection of nucleic acids and their mutations than current enzyme-based detection systems, making 'false positive' results a thing of the past. On the other hand, a novel high resolution acoustic wave microsensor technology property of AWSensors, that allows an accurate, inexpensive, label-free, direct and real time transduction method to quantitatively evaluate the results of the application of the above mentioned DGL© technique. 

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Advance Wave Sensors SL
Destina Genomics Ltd.
Foundation for Research & Technology - Hellas
Servicio Andaluz de Salud - Hospital Universitario San Cecilio Granada
Sistemas Genómicos SL
Université Catholique de Louvain - ICTEAM
Co-funded by the Horizon 2020 Framework Programme of the European Union