Real-Time Cell Sorting with Scalable In Situ FPGA-Accelerated Deep Learning

Precise cell classification is essential in biomedical diagnostics and therapeutic monitoring, particularly for identifying diverse cell types involved in various diseases. Traditional cell classification methods such as flow cytometry depend on molecular labeling which is often costly, time-intensive, and can alter cell integrity. To overcome these limitations, we present a label-free machine learning framework for cell classification, designed for real-time sorting applications using bright-field microscopy images. This approach leverages a teacher-student model architecture enhanced by knowledge distillation, achieving high efficiency and scalability across different cell types. Demonstrated through a use case of classifying lymphocyte subsets, our framework accurately classifies T4, T8, and B cell types with a dataset of 80,000 preprocessed images, accessible via an open-source Python package for easy adaptation. Our teacher model attained 98\% accuracy in differentiating T4 cells from B cells and 93\% accuracy in zero-shot classification between T8 and B cells. Remarkably, our student model operates with only 0.02\% of the teacher model's parameters, enabling field-programmable gate array (FPGA) deployment. Our FPGA-accelerated student model achieves an ultra-low inference latency of just 14.5~$\mu$s and a complete cell detection-to-sorting trigger time of 24.7~$\mu$s, delivering 12x and 40x improvements over the previous state-of-the-art real-time cell analysis algorithm in inference and total latency, respectively, while preserving accuracy comparable to the teacher model. This framework provides a scalable, cost-effective solution for lymphocyte classification, as well as a new SOTA real-time cell sorting implementation for rapid identification of subsets using in situ deep learning on off-the-shelf computing hardware.

MIML: Multiplex Image Machine Learning for High Precision Cell Classification via Mechanical Traits within Microfluidic Systems

Label-free cell classification is advantageous for supplying pristine cells for further use or examination, yet existing techniques frequently fall short in terms of specificity and speed. In this study, we address these limitations through the development of a novel machine learning framework, Multiplex Image Machine Learning (MIML). This architecture uniquely combines label-free cell images with biomechanical property data, harnessing the vast, often underutilized morphological information intrinsic to each cell. By integrating both types of data, our model offers a more holistic understanding of the cellular properties, utilizing morphological information typically discarded in traditional machine learning models. This approach has led to a remarkable 98.3\% accuracy in cell classification, a substantial improvement over models that only consider a single data type. MIML has been proven effective in classifying white blood cells and tumor cells, with potential for broader application due to its inherent flexibility and transfer learning capability. It's particularly effective for cells with similar morphology but distinct biomechanical properties. This innovative approach has significant implications across various fields, from advancing disease diagnostics to understanding cellular behavior.