Biology subjects

Hayden, O.

Publications and source records attributed to Hayden, O..

6 recordsLinked to original sources

bioRxiv2026

SmartSpacer: Design, Implementation, and In-Vitro Validation of a Multimodal Sensorized Knee Spacer for Continuous Infection Monitoring in Two-Stage Revision Arthroplasty

Periprosthetic joint infection (PJI) is the leading cause of failure in two-stage revision total knee arthroplasty (TKA). The timing of reimplantation currently relies on subjective clinical assessment, as no established method enables continuous, objective, local monitoring of infection dynamics during the spacer interval. We present the SmartSpacer, a sensorized antibiotic-loaded PMMA knee spacer integrating a miniaturized PCB within the tibial component (65 x 45 x 12 mm). The system incorporates digital temperature sensors, a CMOS camera module, a spectrometer, an inertial measurement unit, and a Bluetooth Low Energy (BLE) 5.2 transceiver. Firmware was developed on Zephyr RTOS with aggressive power management. Validation experiments covered power consumption profiling, BLE signal transmission through air, phantom liquid, and ex-vivo porcine knee tissue, temperature accuracy against a calibrated PT100 reference, and motion detection in seven healthy volunteers across three activity protocols. Firmware optimization reduced quiescent current from 700-850 {micro}A to 8 {micro}A, projecting a battery life exceeding 600 days at a clinically relevant sampling rate of one image and one spectrum per hour -- more than an order of magnitude beyond the maximum spacer implantation duration. BLE connectivity was maintained reliably up to 6 m through tissue-equivalent phantom liquid and up to 8-9 m in open air. Temperature sensors achieved {+/-}0.16 {degrees}C steady-state accuracy with self-heating artefacts below 0.15 {degrees}C. Motion detection scaled proportionally with activity intensity, though inter-subject variability in crutch-walking indicated that patient-specific calibration will be required. The SmartSpacer introduces an in vivo wearable - a temporary, implantable knee spacer providing continuous, wireless, multiparametric monitoring within the joint space. It has the potential to transform two-stage revision arthroplasty from empirically timed to data-driven, individualized clinical decision-making.

bioengineering↗

bioRxiv2026

Towards In Vivo Wearable Diagnostics in Orthopaedics: Sensorized Bone Cement for Knee Spacer Applications

Periprosthetic joint infection (PJI) is a severe complication of total knee arthroplasty and is a leading cause of revision surgery, and is associated with significant morbidity. Two-stage exchange using antibiotic-loaded polymethylmethacrylate (PMMA) spacers remains the clinical gold standard, yet the decision to reimplant relies largely on indirect markers and clinical judgment, as no method allows continuous in situ assessment of infection resolution. Here, we report a sensorized knee spacer that transforms PMMA bone cement from a passive structural material into an active, wearable diagnostic device. A miniaturized multimodal sensor unit integrating optoelectronic and physicochemical sensing was embedded within the tibial spacer component and wirelessly coupled, enabling energy-efficient, 24/7 in vivo monitoring during the spacer interval for several months. We developed a reproducible encapsulation and integration strategy compatible with clinically realistic spatial, thermal, and mechanical constraints, without altering the established surgical workflow. The functionality of the embedded camera, spectrometer, and temperature sensors following cement integration was verified. Mechanical integrity and signal stability were confirmed under ISO-compliant dynamic biomechanical loading conditions. In vivo validation of the implantable wearable was preclinically demonstrated in a porcine model using human knee spacer dimensions. These findings establish the technical feasibility of sensor-integrated PMMA spacers and introduce bone cement as an enabling platform for smart orthopedic implants. Continuous, local monitoring of the peri-implant environment may open new pathways for evidence-based decision-making in infection management with temporary implantable wearables.

bioengineering↗

bioRxiv2025

CellTrap: A Microfluidic Platform Enabling Cell-Cell Interactions at Variable Effector to Target Ratios

Immune-cancer cell interactions play a central role in understanding antitumor responses and evaluating immunotherapies. However, long-term, single-cell-level analysis of these interactions remains challenging. To address this, we developed a microfluidic trapping device with 1,024 traps, each equipped with a filter to retain cells, sustain medium flow, minimize cross-talk, and allow precise control of effector-to-target (E:T) ratios. The platform enables continuous monitoring of immune-cancer interactions for up to 14 hours. Device characterization was performed using 10 {micro}m fluorescent beads seeded via hydrostatic flow, with trap occupancy validated by Poisson statistics. Initial experiments using PBMCs against GFP-expressing U87 (U87GFP) glioblastoma cells demonstrated an immune-mediated reduction in GFP intensity, which was interpreted cautiously as a cytotoxic response. To improve reproducibility, we subsequently employed IL-2-stimulated Natural Killer cells (NK92IL2) as standardized effectors and evaluated their interactions with U87GFP glioblastoma cells, K562 chronic myelogenous leukemia cells, and LS174T adenocarcinoma cells. Time-lapse imaging revealed transient intracellular calcium fluxes, consistent with early activation of NK92IL2 cells, followed by a cytotoxic response. Increasing E:T ratios consistently enhanced immune activity, highlighting the utility of this device for dissecting immune-cancer interactions and guiding the development of immunotherapy.

bioengineering↗

bioRxiv2025

Fabry-Perot Microscopy for Improved Contrast Enhancement and 3D Cellular Imaging

Fabry-Perot Microscopy (FPM) integrates a lab-on-a-chip optical cavity and tunable light source in a label-free imaging technique that enhances contrast and enables pseudo-three-dimensional imaging in transparent biological samples. By integrating a fixed-length Fabry-Perot cavity into a coated microfluidic cell, FPM selectively highlights structures of defined optical thickness through resonance-based interference. We demonstrate that this architecture preserves lateral resolution while providing up to 20-fold contrast enhancement compared to conventional wide-field microscopy. Using human epithelial cells, blood components, and E. coli bacteria, we show that FPM enables clear visualization of subcellular features and discrimination of cell types. Spectrally resolved image stacks are used to extract pixel-wise optical thickness maps, from which physical thickness and refractive index can be derived. These parameters reveal nanoscale structural differences and offer routes to biophysical characterization. Notably, the system operates without mechanical scanning the cavity, using spectral tuning alone to generate images. FPM is compatible with standard microscope optics, and functions under static or flow-compatible conditions, making it suitable for high-throughput cytometry and in vitro diagnostics. These results establish FPM as a versatile extension to wide-field microscopy, enabling contrast-tunable, quantitative imaging of biomedical specimen.

biophysics↗

bioRxiv2024

Spatiotemporal control of a multilayered co-axial flow in a 3D printed microchannel with cascaded nozzles

Sculpting and stopping multilayered co-flowing streams is challenging due to inhomogeneous pressure distribution within a fluidic circuit composed of multiple interconnected microchannels having variable flow resistances. Here, we have investigated three different flow control methods to effectively stop a multilayered flow inside a 3D-printed microfluidic channel by bringing the average flow velocity from >100 mm s-1 to below a critical velocity of 200 {micro}m s-1 within a certain delay time tD of [~]2s. Firstly, we 3D printed a sequence of three concentric nozzles ([~]75 {micro}m) embedded serially inside the microchannel ([~]200 {micro}m) using a two-photon polymerization (2PP) method. Secondly, we used the 2PP-based 3D printed device to produce a structured coaxial flow of four streams with individual layer thicknesses of O(10 {micro}m) within the outlet section of the microchannel. Thirdly, we removed the pressure gradient across the fluidic circuit, from > 2 bar to [~]0 bar, to stop the multilayered flow and measured tD to assess the performance of the three stop flow methods. During the stop-flow phase, an inhomogeneous pressure gradient across different inlets resulted in a backflow to inlet channels with lower pressures. In the three stop-flow methods investigated, we systemically managed the fluidic capacitance to minimize a dimensionless backflow index (BFI) value from [~]0.3 (worst case) to [~]0.03 (best case) for a total flow rate ranging from 16.8 {micro}l min-1 to 168 {micro}l min-1. Finally, we have recommended the best stop-flow conditions, which resulted in a minimal delay time of tD [~] 2s and a BFI < 0.05.

bioengineering↗

bioRxiv2024

Quantitative Magnetic Flow Cytometry in High Hematocrit Conditions for Point-of-Care Testing

Quantitative cell analysis in liquid biopsies is essential for many clinical decisions, but it is primarily tied to centralized laboratories. However, access to these laboratories is limited in low-resource settings or for immobile patients, highlighting the urgent need for Point-of-Care (POC) testing infrastructure. Magnetic flow cytometers (MFC) offer a solution, albeit sample processing steps like cell lysis or washing crucially disrupt POC-capable MFC workflows. Here, we investigate conditions for immunomagnetic labeling and direct cell quantification in a streamlined workflow suitable for high hematocrit environments. Magnetic nanoparticles (MNP) are characterized by their size, magnetic moment, and potential to generate signal noise, favoring small (< 50 nm) MNPs. Theoretical models provide the framework for quantifying bound MNPs per cell, revealing labeling quality and giving insight into system requirements for reliable cell detection. Temporal labeling dynamics show suboptimal binding kinetics in whole blood (WB), leading to long incubation periods and only 50% recovery of optically determined concentrations. Besides showing quantitative MFC in WB with biomimetic microbeads, we finally quantify CD14+ monocytes in WB with our streamlined workflow, achieving an intra-assay coefficient of variation (CV) of 0.11 and a CV across multiple donors of 0.10, demonstrating reliable POC flow cytometry close to regulatory standards.

bioengineering↗