Design and Validation of a Low-Cost Smartphone Based Fluorescence Detection Platform Compared with Conventional Microplate Readers

Malaria remains a leading cause of mortality in resource-limited settings, where expert microscopists are scarce. Automated diagnosis based on microscopy images thus has strong potential to improve care delivery. But for an algorithm to deploy, a necessary requirement is that it meet a suite of non-obvious (from a machine learning (ML) perspective) clinical constraints. Therefore, in close consultation with a national health center we developed a malaria diagnosis pipeline which addresses key requirements listed by the health care center but typically ignored in the ML malaria literature. In particular, it includes: (i) stopping criteria (to reduce image acquisition and time-to-result); (ii) human-in-the-loop functionality (for review and accountability); (iii) multi-species discrimination (since treatment varies by species); (iv) thick film detection (standard for microscopy); (v) computationally-efficient uncertainty calculations (to aid clinician review); and (vi) an edge device platform (since internet can be spotty in this catchment area). The mobile system performs all inference on-device using YOLOv13n deployed via TensorFlow Lite. It detects four species and white blood cells from Giemsa-stained thick blood smear images, aggregating per-image detections into slide-level parasitemia with World Health Organization (WHO)-standard quantification. This paper highlights these various clinical constraints and offers methods to address them. Evaluated on 2,739 annotated images across all four species, the system achieves mAP@0.5 of 0.863, per-image parasite count correlation of r = 0.812, slide-level r = 0.951 (soft counting, 10 images/slide), and runs entirely offline with a pipeline time of 10.27 +- 1.65 s per image.

High-throughput microfluidic live-cell imaging generates rich single-cell data. Yet semi-automated procedures for locating regions of interest (RoIs), each containing one cell population, and removing surrounding microfluidic structures from recorded images, scale with the number of RoIs. This prevents real-time image analysis and delays time-to-insight by hours to days. We introduce the Design-Aware and Real-Time capable (DART) paradigm for microfluidic cultivation chips, which aligns the CAD blueprint with the physical chip and thereby enables throughput-independent localization of all RoIs and fully automated image processing across diverse RoI geometries and chip layouts. DART establishes this alignment through embedded fiducial markers and deep-learning-based marker detection. We validate DART using the Swiss Army Knife chip, which combines eight structurally distinct RoI designs across 1164 RoI locations. DART localizes all RoIs in five minutes, removes microfluidic structures from raw microscopy images in 40 ms, and performs fully automated image analysis, including cell segmentation, in under 1.1 s per image. Together, these capabilities establish DART as an end-to-end hardware-software paradigm with real-time-capable analysis that paves the way toward closed-loop and outcome-driven smart microscopy.

Counting living cells is an important step in many biological research workflows. Our collaborators at the Wellcome Sanger Institute study vital genes in humans via large scale saturation genome editing screening, which requires repeatedly counting cells a great number of times. Computer Vision based automation is crucial for high throughput and resource efficiency. In this work, we develop a regression-based deep learning computer vision algorithm to detect and count cells in phase-contrast microscopy images. To reduce annotation effort, which in practice often becomes a bottleneck, we focus on counting cells only using sparse point annotations, which are fast and easy to acquire. By comparison to state-of-the-art 0-shot methods, we show that regression-based counting is a promising alternative in low data regimes. Through developing methods to automatically count living cells in microscopy images, we contribute to valuable research on the human genome. The code is available at https://github.com/beijn/cellnet.