Multi-modal transformer for signal classification in nanopore blockade experiments

Nanopores are versatile single-molecular sensors, but their utility is fundamentally constrained by stochastic translocation dynamics warping any encoded information. We resolve it by shifting from time-domain analysis to a learned latent-space mapping via a contrastive encoder trained exclusively on simulated signals from a physics-informed model. This encoder maps solid-state nanopore signals of engineered DNA barcodes into an interpretable molecular coordinate system. The learned representation is responsive to structural barcode parameters while remaining invariant to acquisition conditions and translocation conformation, allowing data pooling across devices. Molecule identification requires a single pass through the encoder, reducing computational cost by three orders of magnitude relative to alignment-based methods. We experimentally validate through mixture quantification, rare-variant detection, consensus barcode reconstruction, and real-time signal acquisition. This shift from temporal analysis to mapping structural coordinates into a latent space changes the paradigm behind analyzing stochastic sensor signals by linking classification to interpretable encoded molecular information.

Motivation: Noisy labels are a common challenge in molecular property prediction because molecular annotations are often obtained from assays, curated databases, or weak annotation pipelines rather than directly observed clean biological states. Treating recorded labels as reliable supervision can cause models to memorize corrupted observations and learn misleading molecular evidence. In multimodal molecular representation learning, this issue can be amplified by graph-text fusion or alignment, which may propagate label-induced errors across modalities. Results: We propose MOLAR, a noise-aware framework for learning multimodal molecular representations from noisy labels. MOLAR separates latent clean-property inference from recorded-label observation: graph and text views contribute residual evidence to a clean-property distribution, and a categorical label-observation channel maps this distribution to recorded labels for training. This formulation derives posterior label reliability and modality-specific molecular evidence from the model. Experiments on naturally noisy molecular benchmarks and controlled label-flipping benchmarks show that MOLAR consistently outperforms representative baselines. Visualization analyses further show that MOLAR provides interpretable reliability and modality-evidence diagnostics.

Accurate on-device fluid identification is essential for microfluidic applications, yet maintaining reliability under varying flow, pressure, and temperature remains a key challenge. Existing learning-based methods often treat sensor signals as domain-agnostic features, neglecting the underlying physical relationships that govern fluid behavior, thereby limiting generalization and interpretability. To address this, we propose PRIMS, a physics-aware multimodal Transformer that integrates physical knowledge into representation learning and attention mechanisms through three dedicated modules: (1) Physics-based Token Vectorization transforms raw Coriolis and pressure sensor signals into physically meaningful token embeddings; (2) Physical Component Synthesizer models viscosity-related dependencies among flow, pressure, and density; and (3) Physics-guided Fusion captures cross-physical correlations through attention-based integration. By embedding these physics-based relationships directly into the model architecture, PRIMS bridges analytical fluid mechanics and deep learning, enabling interpretable, data-efficient, and resilient fluid classification. Evaluations on a five-fluid benchmark under dynamic flow, pressure, and temperature conditions show that PRIMS achieves 98.92% average F1-score with only 0.46 million parameters, a 14 times reduction compared to state-of-the-art Transformer-based methods. PRIMS also consistently outperforms prior SOTA models under out-of-distribution shifts to unseen temperature ranges and unseen flow-rate ranges, indicating strong robustness to operating conditions not observed during training. These findings suggest that designing architectures that explicitly mirror governing physical relationships can make them learn transferable, environment-independent representations, improving real-world reliability for microfluidic sensing.