AT4LB Platform
Precision Liquid Biopsy, Powered by HFF-QCMD Arrays
AT4LB Platform combines advanced HFF-QCMD array technology with liquid biopsy to enable highly sensitive detection of ESR1 mutations from a simple blood sample. Designed for precision oncology, the platform provides robust and reliable molecular insights that support longitudinal breast cancer monitoring, allowing clinicians to track tumor evolution over time. By identifying clinically relevant mutations with high sensitivity, AT4LB helps inform personalized treatment strategies, optimize therapeutic decision-making, and support better patient management throughout the course of the disease.
How AT4LB Works
XPOTDx is developing an ultra-sensitive and cost-effective HFF-QCMD sensing platform for the detection of circulating tumour DNA (ctDNA) mutations in liquid biopsy, enabling rapid, minimally invasive cancer diagnosis, treatment selection and ongoing patient monitoring. We are working towards ISO 13485 certification and IVDR Class C regulatory approval, ensuring the XPOTDx platform meets the highest international standards required for clinical in vitro diagnostic use, targeting both European and global markets including FDA clearance in the United States.
The AT4LB workflow is simple and powerful:
Step 1: Liquid Biopsy: A routine blood draw is all that is needed. No surgery, no tissue extraction.
Step 2: Plasma Separation: Blood is centrifuged to separate the plasma, which is then directly used as the sample input.
Step 3: AS-PCR Amplification & Detection: The plasma sample is loaded directly into the XPOTDx integrated cartridge, where allele-specific PCR selectively amplifies mutant cancer DNA targets simultaneously alongside normal DNA, inside a sealed, precision-controlled microfluidic carousel handling up to 12 samples per run.
Step 4: Acoustic Array Detection: The platform features a proprietary array of 24 HFF-QCMD sensors, enabling true multiplexing, detecting multiple cancer gene mutations across multiple patient samples simultaneously in a single run. Lipid nanoparticles bind exclusively to mutant amplicons, generating distinctive acoustic signals detected in real time across the entire sensor array.
Step 5: Real-Time Results: Acoustic signals are automatically converted into amplification curves, delivering clear, clinically actionable results, supporting oncologists in both treatment decisions and longitudinal patient monitoring.
AT4LB Technology
HFF-QCMD ACOUSTIC RESONATOR ARRAYS
While QCMD has long been established as a powerful sensing technique in research laboratories, its translation into clinical diagnostics has been limited by insufficient sensitivity and high device costs. Advanced Wave Sensors (AWS) changed that, pioneering the development of High Fundamental Frequency QCMD (HFF-QCMD) sensors and monolithic HFF resonator arrays specifically engineered for diagnostic applications. The result is a 24-sensor array biochip delivering dramatically higher sensitivity, faster response times, and significantly reduced costs in sensors, reagents and sample volumes, making acoustic biosensing viable for routine clinical use for the first time.
The X24 prototype platform, built to monitor this array in real time, is the technological foundation of the XPOTDx AT4LB system.
Key Publications:
- Fernández et al. HFF Monolithic Resonator Arrays for Biosensing Applications. IEEE Sensors Journal, 21(1), 284-295, 2021.
- Calero et al. A Multichannel Microfluidic Sensing Cartridge for Bioanalytical Applications of Monolithic QCM. Biosensors, 10, 189, 2020.
ACOUSTIC SIGNAL AMPLIFICATION. HOW WE HEAR CANCER’S WHISPER
The exceptional sensitivity of the XPOTDx platform comes from a patented acoustic signal amplification method developed by our scientific founders at FORTH. By exploiting the relationship between the acoustic dissipation signal of the HFF-QCMD sensor, the geometry of molecules or particles attached to its surface, and the mechanical properties of the molecular linker, we engineered an approach where lipid nanoparticles (liposomes) or polymeric particles act as acoustic amplifiers, binding exclusively to mutant DNA targets immobilised on the sensor surface. This generates a dramatically enhanced dissipation signal, allowing the platform to detect 1 mutant DNA copy in the presence of 10,000 normal DNA copies, achieving a sensitivity of 0.01%. This has been demonstrated for KRAS G12D, BRAF V600E and the BRCA1 gene, key diagnostic and prognostic biomarkers for colorectal, melanoma and breast cancer respectively.
Key Publications:
- Papadakis et al. Acoustic sensing of different DNAs based on their length. Anal. Methods, 2014. – Milioni et al. Acoustic Methodology Selecting Highly Dissipative Probes for Ultrasensitive DNA Detection. Anal. Chem. 92, 8186, 2020.
- Gizeli E. et al. PCT/EP2016/065612 (Patent: Measurement of analyte with an acoustic wave sensor).
- Naoumi et al. Acoustic Array Biochip Combined with AS-PCR for Multiple Cancer Mutation Analysis. ACS Sensors, 7(2), 495-503, 202
- Milioni et al. Acoustic Methodology for Selecting Highly Dissipative Probes for Ultrasensitive DNA Detection. Anal. Chem. 92, 8186, 2020.
