Microfluidic shape-based separation for cells and particles: recent progress and future perspective.

Passive microfluidic devices for cell separation

We investigate the migration of particles of different geometrical shapes and sizes in a scaled-up model of a gravity-driven deterministic lateral displacement (g-DLD) device. Specifically, particles move through a square array of cylindrical posts as they settle in a quiescent fluid under the action of gravity. We performed experiments that cover a broad range of orientations of the driving force (gravity) with respect to the columns (or rows) in the square array of posts. We observe that as the forcing angle increases, particles initially locked to move parallel to the columns in the array begin to move across the columns of obstacles and migrate at angles different from zero. We measure the probability that a particle would move across a column of obstacles, and define the critical angle θ c as the forcing angle at which this probability is 1/2. We show that critical angle depends on both particle size and shape, thus enabling both size- and shape-based separations. Finally, we show that using the diameter of the inscribed sphere as the characteristic size of the particles, the corresponding critical angle becomes independent of particle shape and the relationship between them is linear. This linear and possibly universal behavior of the critical angle as a function of the diameter of the inscribed sphere of the particles could provide guidance in the design and optimization of g-DLD devices used for shape-based separation.

Deterministic lateral displacement (DLD) is a common name given to a class of continuous microfluidic separation devices that use a repeating array of pillars to selectively displace particles having a mean diameter greater than the critical diameter (Dc). This Dc is an emergent property influenced by pillar shape, size, and spacing, in addition to the suspending fluid and target particle properties. The majority of previous research in DLD applications has focused on the utilization of laminar flow in low Reynolds number (Re) regimes. While laminar flow exhibits uniform streamlines and predictable separation characteristics, this low-Re regime is dependent on relatively low fluid velocities, and may not hold true at higher processing speeds. Through numerical modeling and experimentation, we investigated high-Re flow characteristics and potential separation enhancements resulting from vortex generation within a DLD array. We used an analytical model and computational software to simulate DLD performance spanning a Re range of 1–100 at flow rates of 2–170 μL/s (0.15–10 mL/min). Each simulated DLD array configuration was composed of 60 μm cylindrical pillars with a 45 μm gap size. The experimental DLD device was fabricated using conventional soft lithography, and injected with 20 μm particles at varying flow rates to observe particle trajectories. The simulated results predict a shift in Dc at Re > 50, while the experimental results indicate a breakdown of typical DLD operation at Re > 70.

The advent of microfluidics in the 1990s promised a revolution in multiple industries from healthcare to chemical processing. Deterministic lateral displacement (DLD) is a continuous-flow microfluidic particle separation method discovered in 2004 that has been applied successfully and widely to the separation of blood cells, yeast, spores, bacteria, viruses, DNA, droplets, and more. Deterministic lateral displacement is conceptually simple and can deliver consistent performance over a wide range of flow rates and particle concentrations. Despite wide use and in-depth study, DLD has not yet been fully elucidated or optimized, with different approaches to the same problem yielding varying results. We endeavor here to provide up-to-date expert opinion on the state-of-art and current fundamental, practical, and commercial challenges with DLD as well as describe experimental and modeling opportunities. Because these challenges and opportunities arise from constraints on hydrodynamics, fabrication, and operation at the micro- and nanoscale, we expect this Perspective to serve as a guide for the broader micro- and nanofluidic community to identify and to address open questions in the field.

Lattice Boltzmann simulations of pinched flow fractionation

This Theme Issue is dedicated to the memory of Tom Duke, who passed away in 2012 at the age of 48. Tom made lasting contributions to a broad range of topics and was highly regarded for his very elegant approaches that unravel key physical principles underlying the function of biological systems.

In pursue of a comfortable vehicle driving in different road profiles, intelligent methods used to improve the suspension system of the vehicle. Semi-active suspension system outperformed other suspension systems because it contains an intelligent actuator that can give the appropriate force to dissipate unwanted vibration using intelligent and real-time controllers. Here in this paper MR fluid damper with Fuzzy-PID controller examined to optimized using modified DE algorithm. However, in the Fuzzy-PID controller, the fuzzy logic algorithm is used to autotune the PID controller, but it cannot be considered as a fully real-time controller since the fuzzy algorithm uses a previous knowledge base built offline. The offline design of Fuzzy algorithm cannot cope with real-time unexpected vibrations occurred while driving car in different road profiles. In this paper, a Fuzzy-DE-PID controller proposed based on modified DE algorithm to enhance the Fuzzy logic gains in order to increase vehicle semi-active suspension system performance. To prove the effectiveness of the proposed controllers, a simulation and experimental tests were conducted using the proposed controller with different disturbances. The results of the simulation and the experimental tests for the proposed controller showed improvement of the vehicle’s ride comfort over the Fuzzy-PID and the passive system. We believe that using this proposed controller in any other real-time application will improve the performance to the highest levels without the need for a previous knowledge base for designing a real-time Fuzzy-PID controller.

Exploiting phase change materials in tunable passive heating system for low-resource point-of-care diagnostics

Wireless power transfer (WPT) systems are widely used in various applications due to their convenience and efficiency. However, the performance of WPT systems can be significantly affected by misalignment and load variations. This letter proposes a method to estimate mutual inductance (<italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</i>) and load resistance (<inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">${{R}_L})$</tex-math></inline-formula> in WPT systems using total harmonic distortion (THD) of input current. A numerical method to estimate these parameters has been developed by deriving an analytical relationship between THD, <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</i>, and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">${{R}_L}$</tex-math></inline-formula>. Experimental validation demonstrates that the proposed method provides accurate estimates of <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</i> and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">${{R}_L}$</tex-math></inline-formula> under varying conditions by only using transmitter current, with maximum estimation errors of 5.1% for <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</i> and 3.6% for <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">${{R}_L}$</tex-math></inline-formula> when estimated separately by keeping the other parameter constant. The proposed method is extended to simultaneously estimate <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</i> and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R_L</i> with a maximum estimation error of 4.9%. This method can be adopted for real-time monitoring and control strategies, such as frequency control, system identification, and diagnostic applications, in WPT systems.

Biophysical Cytometry In article number 2201463, Carlos Honrado, Nathan S. Swami, and co-workers present integration of multichannel impedance cytometry downstream of high throughput microfluidic cell separation that is presented for on-chip multiparametric phenotypic validation of the enrichment of activated macrophages from a heterogeneous sample, without any sample loss, bias or dilution.

The integration of daylighting element into sustainable building design presents a significant opportunity to reduce energy consumption while improving indoor environmental quality. This study focuses on the performance assessment of passive daylight transport systems, with an emphasis on their thermal and optical characteristics. Various configurations of tubular daylighting devices were analyzed using simulation-based methods, considering material properties, geometrical parameters, and hygrothermal conditions of the building envelope. The evaluation considered both the efficiency of light transmission and the impact on thermal integrity, including potential heat loss through envelope penetrations. The results demonstrate that the proper design and positioning of daylighting elements can significantly enhance visual comfort without compromising energy performance. The findings support the implementation of daylight-driven strategies as a viable approach to improve building sustainability and contribute to nearly zero-energy building standards.

The rapid evolution of Artificial Intelligence (AI) has significantly transformed the capabilities, performance, and autonomy of modern mechatronic systems. As industries transition toward intelligent and interconnected manufacturing environments, AI has emerged as a powerful enabler of real-time decision-making, adaptive control, predictive maintenance, and autonomous operation. This review provides a comprehensive analysis of AI integration within mechatronic systems, examining its influence on system performance, autonomy, and manufacturing efficiency. Key AI techniques including machine learning, deep learning, reinforcement learning, evolutionary optimization, and computer vision are evaluated in terms of their applications in control, sensing, diagnostics, and robotics. The paper also highlights advancements in AI-driven motion control, autonomous navigation, sensor fusion, and smart factory operations. Critical challenges such as data requirements, computational constraints, system interoperability, and safety concerns are discussed to identify research gaps. Finally, emerging trends and future directions, such as edge AI, digital twins, explainable AI, and fully autonomous mechatronic cells, are explored. This review consolidates current knowledge and provides insights to guide researchers and practitioners in developing next-generation intelligent mechatronic systems capable of supporting the demands of Industry 4.0 and beyond.

A high-speed, 11-parameter, 6-color fluorescence, laser flow cytometer/cell sorter with a number of special and unique features has been built for ultrasensitive detection and isolation of rare cells for clinical diagnostics and therapeutics. The software for real-time data acquisition and sort control, written as C ++ programming language modules with a Windows TM graphical user interface, runs on a 66-MHz 80486 computer joined by an extended bus to 23 sophisticated multi-layered boards of special data acquisition and sorting electronics. Special features include: high-speed (> 100,000 cells/sec) real-time data classification module (U.S. Patent 5,204,884 (1993)); real-time principal component cell sorting; multi-queue signal-processing system with multiple hardware and software event buffers to reduce instrument dead time, LUT charge-pulse definition, high-resolution `flexible' sorting for optimal yield/purity sort strategies (U.S. Patent 5,199,576); pre-focusing optical wavelength correction for a second laser beam; and two trains of three fluorescence detectors-- each adjustable for spatial separation to interrogate only one of two laser beams, syringe- driven or pressure-driven fluidics, and time-windowed parameters. The system has been built to be both expandable and versatile through the use of LUT's and a modular hardware and software design. The instrument is especially useful at detection and isolation of rare cell subpopulations for which our laboratory is well-known. Cell subpopulations at frequencies as small as 10 -7 have been successfully studied with this system. Current applications in clinical diagnostics and therapeutics include detection and isolation of (1) fetal cells from material blood for prenatal diagnosis of birth defects, (2) hematopoietic stem and precursor cells for autologous bone marrow transplantation, (3) metastatic breast cancer cells for molecular characterization, and (4) HIV-infected maternal cells in newborn blood to study mother-to-infant vertical transmission of AIDS.

Ultrasound contrast agents (UCAs) have the potential to nucleate cavitation and promote both beneficial and deleterious bioeffects in vivo. Previous studies have elucidated the pulse-duration-dependent pressure amplitude threshold for rapid loss of echogenicity due to UCA fragmentation. Previous studies have demonstrated that UCA fragmentation was concomitant with inertial cavitation. The purpose of this study was to evaluate the relationship between stable and inertial cavitation thresholds and loss of echogenicity of UCAs as a function of pulse duration. Determining the relationship between cavitation thresholds and loss of echogenicity of UCAs would enable monitoring of cavitation based upon the onscreen echogenicity in clinical applications. Two lipid-shelled UCAs, echogenic liposomes (ELIP) and Definity®, were insonified by a clinical ultrasound scanner in duplex spectral Doppler mode at four pulse durations (‘sample volumes’) in both a static system and a flow system. Cavitation emissions from the UCAs insonified by Doppler pulses were recorded using a passive cavitation detection system and stable and inertial cavitation thresholds ascertained. Loss of echogenicity from ELIP and Definity® was assessed within regions of interest on B-mode images. A numerical model based on UCA rupture predicted the functional form of the loss of echogenicity from ELIP and Definity®. Stable and inertial cavitation thresholds were found to have a weak dependence on pulse duration. Stable cavitation thresholds were lower than inertial cavitation thresholds. The power of cavitation emissions was an exponential function of the loss of echogenicity over the investigated range of acoustic pressures. Both ELIP and Definity® lost more than 80% echogenicity before the onset of stable or inertial cavitation. Once this level of echogenicity loss occurred, both stable and inertial cavitation were detected in the physiologic flow phantom. These results imply that stable and inertial cavitation are necessary in order to trigger complete loss of echogenicity acoustically from UCAs and this finding can be used when planning diagnostic and therapeutic applications.

Fuzzy logic based control systems provide a simple and efficient method to control highly complex and imprecise systems. However, the lack of a simple hardware design that is capable of modifying the fuzzy controller's parameters to adapt for any changes in the operation environment, or behavior of the plant system limits the applicability of fuzzy based control systems in the automotive and industrial environments. The design and implementation of an FPGA based fuzzy logic controller, that allows real-time modification of its membership functions and rule base is introduced in this paper. The development of the controller's architecture is carried out on a National Instruments Intelligent DAQ board (PCI-7833R) with a reconfigurable Xilinx Virtex-II FPGA. The proposed design combines the performance advantages of existing static FPGA based fuzzy control architectures, with the flexibility and ease of implementation of conventional micro-controllers and general purpose processors. To test the efficiency of the controller and its ability to stabilize a highly dynamic system, a semi-active suspension system was developed. Simulation results for the proposed FPGA controller showed a 56% characteristic enhancement over the standard passive suspension system.