Open research questions in Microfluidic and Bio-sensing Technologies

What the literature leaves open

• The study does not provide a quantitative readout of a levitated sample’s orientation without a calibrator. The framework may exhibit temporal jitter in independent per-frame predictions. The dataset for cell-calibrator adherence is limited to 242 frames.

  Synthetic-to-Real 5D Pose Estimation for Acoustically Levitated Micro-Calibrators in Lab-on-a-Chip Devices · 2026 · DOI

• The assumption of blood as a Newtonian fluid may not capture its shear-thinning behavior. The two-dimensional geometry used in simulations may neglect certain three-dimensional effects. The paper identifies the need for non-Newtonian models to represent blood's shear-thinning properties accurately.

  Intelligent Microfluidics for Plasma Separation: Integrating Computational Fluid Dynamics and Machine Learning for Optimized Microchannel Design · 2025 · DOI

• Traditional methods for CTC detection have limitations such as high false-positive rates and poor practicality.

  Advancements in Circulating Tumor Cell Detection for Early Cancer Diagnosis: An Integration of Machine Learning Algorithms with Microfluidic Technologies · 2025 · DOI

• The existing in vitro and animal studies have limitations in replicating human systems and organs. There is a need for more accurate and reliable methods for disease modeling and drug screening. The integration of biosensors with organoids has the potential to address these limitations.

  Sophisticated Interfaces Between Biosensors and Organoids: Advancing Towards Intelligent Multimodal Monitoring Physiological Parameters · 2025 · DOI

• Future system upgrades may include adaptive laser power control. More advanced image classification algorithms may be incorporated. The incorporation of multi-channel microfluidic architectures to enable parallel sorting may be explored. Sorting more complex biological particle populations, such as cells at different stages of the cell cycle or extracellular vesicles (EVs), may be investigated.

  Fluorescence Imaging-Activated Microfluidic Particle Sorting Using Optical Tweezers · 2025 · DOI

• Traditional techniques such as FACS and MACS have significant limitations. FACS systems are often bulky, expensive, and require complex fluidic handling and precise optical alignment. MACS is constrained by its dependence on magnetic labeling, which is not universally compatible with all sample types and may introduce biological invasiveness.

  Fluorescence Imaging-Activated Microfluidic Particle Sorting Using Optical Tweezers · 2025 · DOI

• Most studies have focused on monitoring cellular behavior through impedance changes, with less emphasis on interpreting the biological significance of impedance signals. Traditional methods for drug evaluation have limitations, such as being invasive and failing to capture dynamic cellular responses.

  Quantitative IC50 Analysis of Puromycin-Induced Cytotoxicity in NIH/3T3 Cells Using a Multi-Well Array Impedance Biosensor · 2025 · DOI

• Lack of accurate interpretation of EIS measurements of cell growth dynamics. Need for theoretical equivalent circuit models for single-cell sensing systems.

  Equivalent Circuit Modeling and Analysis for Microfluidic Electrical Impedance Monitoring of Single-Cell Growth · 2025 · DOI

• Need for a device that can increase the viscoelastic force on particles for single-stream focusing.

  Improving the Enrichment of Submicron-Sized Particles by Size Decreasing of Cruciform Cross-Sectional Microchannel in Viscoelastic Microfluidics · 2025 · DOI

• Traditional diagnostic methods have limitations such as labor-intensive sample preparation and variability. Microfluidic technologies have the potential to address these limitations, but require further development. There is a need for a robust and accessible tool for decentralized diagnostics.

  Handheld Lab-on-a-Chip System for Label-Free Dual-Plex Detection of Biomarkers Through On-Chip Plasma Separation · 2025 · DOI

• Conventional approaches to characterize cancer stem cells have limitations. There is a need for a label-free method to detect cancer stem cells. The plastic phenotype of cancer stem cells makes them challenging to isolate and characterize.

  Ultra-High-Frequency-Dielectrophoresis Microfluidic Biosensor to Detect the Transformation Potential of Extracellular Vesicles Derived from Cancer Stem Cells · 2025 · DOI

• Conventional optical density methods have limitations, including light scattering, turbidity, and an inability to distinguish between live and dead cells. Electrochemical impedance analysis is a promising alternative, but requires further development for real-time monitoring of cell growth.

  AI-Assisted Impedance Biosensing of Yeast Cell Concentration · 2025 · DOI

• The lack of a direct computational relationship between cellular morphology and electrical properties. The need for a method to identify and subtract morphology-dependent components from measured capacitance changes.

  Deep Learning-Based Prediction of Individual Cell α-Dispersion Capacitance from Morphological Features · 2025 · DOI

• The transition of electric field-based technologies from laboratory proof-of-concept to large-scale implementation is a significant challenge. Complex mixed-species biofilms introduce additional limitations, such as EPS-mediated shielding and steep micro-gradients.

  Electric Field Effects on Microbial Cell Properties: Implications for Detection and Control in Wastewater Systems · 2025 · DOI

• Further research is needed to investigate the relationship between cellular morphology and electrical properties in different cell types and experimental conditions. The development of more advanced models that can account for the complex interactions between cellular morphology, electrical properties, and environmental factors could lead to improved predictions and a deeper understanding of cellular behavior.

  Deep Learning-Based Prediction of Individual Cell α-Dispersion Capacitance from Morphological Features · 2025 · DOI

• Many studies have focused on advancing high dimensional single cell analysis; however, strategies to maximize cell sorting recovery in the context of deep immunophenotyping remain poorly defined.

  Optimizing Cell Sorting Performance: A Comparative Study Utilizing Spectral Flow Cytometry · 2026 · DOI

• Sorter-induced cell stress (SICS) is a recognized challenge within the fluorescence-activated cell sorting (FACS) community; however, it remains significantly underreported in the scientific literature, with limited studies proposing effective mitigation strategies.

  Pluronic Acid Prevents Sorter‐Induced Cell Stress in Myeloid Cells From Mouse Peritoneal Cavity · 2025 · DOI

• Current methods for assessing cell invasiveness are complex, invasive, and may disrupt the physiological state of live cells. Most existing in vivo detection methods rely on mouse models, which are associated with long experimental durations, high costs, and limited suitability for reproducibility studies.

  Evaluation of Cancer Cell Invasion Ability Based on Electrochemical Impedance · 2025 · DOI

• Investigating the use of other shapes or materials for the calibrator. Exploring the application of the framework to other types of lab-on-a-chip devices. Improving the temporal consistency of the framework.

  Synthetic-to-Real 5D Pose Estimation for Acoustically Levitated Micro-Calibrators in Lab-on-a-Chip Devices · 2026 · DOI

• Detecting analytes at low concentrations remains challenging, - The inherently low efficiency of Raman scattering, - Conventional optical tweezers are limited in their ability to control microscale MNMs, - The slow molecular diffusion limits detection…

  SERS-Active Micro/Nanomachines for Biosensing · 2025 · DOI

• Low cell lysis efficiency in electric field-based lysis methods. Cell loss and low throughput cell lysis due to the use of syringe pumps for flow cells in and out of the microfluidics channel.

  The Pre-Polarization and Concentration of Cells near Micro-Electrodes Using AC Electric Fields Enhances the Electrical Cell Lysis in a Sessile Drop · 2025 · DOI

• Investigating the effects of different blockage ratios and PEO concentrations on the elasto-inertial focusing - Exploring the application of the device for other types of biological samples - Developing more advanced microfluidic devices for the manipulation of submicron-sized…

  Improving the Enrichment of Submicron-Sized Particles by Size Decreasing of Cruciform Cross-Sectional Microchannel in Viscoelastic Microfluidics · 2025 · DOI

• Studying responses to therapy and prevent relapses, - Monitoring CSC-derived EVs…

  Ultra-High-Frequency-Dielectrophoresis Microfluidic Biosensor to Detect the Transformation Potential of Extracellular Vesicles Derived from Cancer Stem Cells · 2025 · DOI

• Potential applications in drug screening, - Potential applications in cytotoxicity evaluation, - Potential applications in real-time biological…

  Real-Time Monitoring of NIH/3T3 Cell Growth and Drug Reaction Using Impedance Biosensors and Comparison with Biological Assays · 2025 · DOI

• Integration of EF-based platforms with biosensors, machine learning, and real-time analytics for enhanced environmental surveillance - Exploring electric field-based technologies in wastewater…

  Electric Field Effects on Microbial Cell Properties: Implications for Detection and Control in Wastewater Systems · 2025 · DOI

Most-cited papers in Microfluidic and Bio-sensing Technologies

• Acoustical tweezers · The Journal of the Acoustical Society of America · 1991 · 410 citations
• Droplet-based microfluidics · Nature Reviews Methods Primers · 2023 · 306 citations
• Spatially selective manipulation of cells with single-beam acoustical tweezers · Nature Communications · 2020 · 247 citations
• 3D-Printed Microfluidic Device for the Detection of Pathogenic Bacteria Using Size-based Separation in Helical Channel with Trapezoid Cross-Section · Scientific Reports · 2015 · 246 citations
• Single-cell microfluidic impedance cytometry: from raw signals to cell phenotypes using data analytics · Lab on a Chip · 2020 · 226 citations
• Harmonic acoustics for dynamic and selective particle manipulation · Nature Materials · 2022 · 221 citations
• Profiling lymphocyte interactions at the single-cell level by microfluidic cell pairing · Nature Communications · 2015 · 182 citations
• Recent advances in droplet microfluidics for single-cell analysis · TrAC Trends in Analytical Chemistry · 2023 · 179 citations
• Forensic DNA Analysis on Microfluidic Devices: A Review · Journal of Forensic Sciences · 2007 · 152 citations
• Magnetic Levitation in Chemistry, Materials Science, and Biochemistry · Angewandte Chemie International Edition · 2020 · 114 citations

Most recent work

• Recent advances and challenges of manipulation of micro- and nanoparticles by surface acoustic wave in microfluidics · Chaos Solitons & Fractals · 2026
• Blood microfluidics: progress and challenges · Lab on a Chip · 2026
• Flexible, stretchable, on-chip optical tweezers for high-throughput bioparticle manipulation · Light Science & Applications · 2026
• Microfluidic shape-based separation for cells and particles: recent progress and future perspective · Lab on a Chip · 2026
• Advancing non-faradaic impedance biosensors: sensitivity enhancement strategies using microfluidics, multiscale labeling, and CMOS technology · Microsystems & Nanoengineering · 2026
• Non-invasive imaging of cell-based therapies using acoustic reporter genes · bioRxiv · 2026
• Microfluidics for cell therapy and manufacturing in oncology and regenerative medicine · Lab on a Chip · 2026
• Acoustic separation and isolation of viruses, small extracellular vesicles and other nanoscale bioparticles · Nature Protocols · 2026
• Integrated DEP presorting and wireless electrode array for high-throughput selective single-cell isolation · Lab on a Chip · 2026
• Cascading inertial microfluidics for high-throughput, multi-scale enrichment of tumor cells and intact clusters towards enhanced malignancy diagnosis · Microsystems & Nanoengineering · 2026

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