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One of the most popular methods to fabricate biomedical microfluidic devices is by using a soft-lithography technique. However, the fabrication of the moulds to produce microfluidic devices, such as SU-8 moulds, usually requires a cleanroom environment that can be quite costly. Therefore, many efforts have been made to develop low-cost alternatives for the fabrication of microstructures, avoiding the use of cleanroom facilities. Recently, low-cost techniques without cleanroom facilities that feature aspect ratios more than 20, for fabricating those SU-8 moulds have been gaining popularity among biomedical research community. In those techniques, Ultraviolet (UV) exposure equipment, commonly used in the Printed Circuit Board (PCB) industry, replaces the more expensive and less available Mask Aligner that has been used in the last 15 years for SU-8 patterning. Alternatively, non-lithographic low-cost techniques, due to their ability for large-scale production, have increased the interest of the industrial and research community to develop simple, rapid and low-cost microfluidic structures. These alternative techniques include Print and Peel methods (PAP), laserjet, solid ink, cutting plotters or micromilling, that use equipment available in almost all laboratories and offices. An example is the xurography technique that uses a cutting plotter machine and adhesive vinyl films to generate the master moulds to fabricate microfluidic channels. In this review, we present a selection of the most recent lithographic and non-lithographic low-cost techniques to fabricate microfluidic structures, focused on the features and limitations of each technique. Only microfabrication methods that do not require the use of cleanrooms are considered. Additionally, potential applications of these microfluidic devices in biomedical engineering are presented with some illustrative examples.

One of the most popular methods to fabricate biomedical microfluidic devices is by using a soft lithography technique. However, the fabrication of the moulds to produce microfluidic devices, such as SU-8 moulds, usually requires a cleanroom environment that can be quite costly. Therefore, many efforts have been made to develop low-cost alternatives for the fabrication of microstructures, avoiding the use of cleanroom facilities. Recently, low-cost techniques without cleanroom facilities that feature aspect ratios more than 20, for fabricating those SU-8 moulds have been gaining popularity among biomedical research community. In those techniques, Ultraviolet (UV) exposure equipment, commonly used in the Printed Circuit Board (PCB) industry, replaces the more expensive and less available Mask Aligner that has been used in the last 15 years for SU-8 patterning. Alternatively, non-lithographic low-cost techniques, due to their ability for large-scale production, have increased the interest of the industrial and research community to develop simple, rapid and low-cost microfluidic structures. These alternative techniques include Print and Peel methods (PAP), laserjet, solid ink, cutting plotters or micromilling, that use equipment available in almost all laboratories and offices. An example is the xurography technique that uses a cutting plotter machine and adhesive vinyl films to generate the master moulds to fabricate microfluidic channels. In this review, we present a selection of the most recent lithographic and non lithographic low-cost techniques to fabricate microfluidic structures, focused on the features and limitations of each technique. Only microfabrication methods that do not require the use of cleanrooms are considered. Additionally, potential applications of these microfluidic devices in biomedical engineering are presented with some illustrative examples.

The rapid evolution of healthcare technology is being driven by advancements in Micro-Electro-Mechanical Systems (MEMS), BioMEMS (Biological MEMS), and the expanding concept of the Internet of Bodies (IoB). This review explores the convergence of these three domains and their transformative impact on personalized medicine (PM), with a focus on smart, connected biomedical devices. Starting from the historical development of MEMS for medical sensing and diagnostics, the review traces the emergence of BioMEMS as biocompatible, minimally invasive solutions for continuous monitoring and real-time intervention. The integration of such devices within the IoB ecosystem enables data-driven, remote, and predictive healthcare, offering tailored diagnostics and treatment for chronic and acute conditions alike. The paper classifies IoB-associated technologies into non-invasive, invasive, and incorporated devices, reviewing wearable systems such as smart bracelets, e-tattoos, and smart footwear, as well as internal devices including implantable and ingestible. Alongside these opportunities, significant challenges persist, particularly in device biocompatibility, data interoperability, cybersecurity, and ethical regulation. By synthesizing recent advances and critical perspectives, this review aims to provide a comprehensive understanding of the current landscape, clinical potential, and future directions of MEMS, BioMEMS, and IoB-enabled personalized healthcare.

The success of labs- and organs-on-chips as transformative technologies in the biomedical arena relies on our capacity of solving some current challenges related to their design, modeling, manufacturability, and usability. Among present needs for the industrial scalability and impact promotion of these bio-devices, their sustainable mass production constitutes a breakthrough for reaching the desired level of repeatability in systematic testing procedures based on labs- and organs-on-chips. The use of adequate biomaterials for cell-culture processes and the achievement of the multi-scale features required, for in vitro modeling the physiological interactions among cells, tissues, and organoids, which prove to be demanding requirements in terms of production. This study presents an innovative synergistic combination of technologies, including: laser stereolithography, laser material processing on micro-scale, electroforming, and micro-injection molding, which enables the rapid creation of multi-scale mold cavities for the industrial production of labs- and organs-on-chips using thermoplastics apt for in vitro testing. The procedure is validated by the design, rapid prototyping, mass production, and preliminary testing with human mesenchymal stem cells of a conceptual multi-organ-on-chip platform, which is conceived for future studies linked to modeling cell-to-cell communication, understanding cell-material interactions, and studying metastatic processes.

Advances in the intratumor measurement of drug responses have included a pioneering biomedical microdevice for high throughput drug screening in vivo, which was further advanced by integrating a graded-index lens based two-dimensional fluorescence micro-endoscope to monitor tissue responses in situ across time. While the previous system provided a bulk measurement of both drug delivery and tissue response from a given region of the tumor, it was incapable of visualizing drug distribution and tissue responses in a three-dimensional (3D) way, thus missing the critical relationship between drug concentration and effect. Here we demonstrate a next-generation system that couples multiplexed intratumor drug release with continuous 3D spatial imaging of the tumor microenvironment via the integration of a miniaturized two-photon micro-endoscope. This enables optical sectioning within the live tissue microenvironment to effectively profile the entire tumor region adjacent to the microdevice across time. Using this novel microimaging-microdevice (MI-MD) system, we successfully demonstrated the four-dimensional imaging (3 spatial dimensions plus time) of local drug delivery in tissue phantom and tumors. Future studies include the use of the MI-MD system for monitoring of localized intra-tissue drug release and concurrent measurement of tissue responses in live organisms, with applications to study drug resistance due to nonuniform drug distribution in tumors, or immune cell responses to anti-cancer agents.

We analytically investigate the feasibility of long graded-index (GRIN)-lens-based microendoscopes through wavefront shaping. Following the very well-defined ray trajectories in a GRIN lens, mode-dependent phase delay is first determined. Then, the phase compensation needed for obtaining diffraction limited resolution is derived. Finally, the diffraction pattern of the lens output is computed using the Rayleigh–Sommerfeld diffraction theory. We show that diffraction-limited resolution is obtained for a 0.5 mm diameter lens with a length over 1 m. It is also demonstrated that different imaging working distances (WDs) can be realized by modifying the phase compensation. When a short design WD is used, a large imaging numerical aperture (NA) higher than 0.4 is achievable even when a low NA lens (NA = 0.1) is used. The long- and thin-GRIN-lens-based microendoscope investigated here, which is attractive for biomedical applications, is being prioritized for use in a clinical stage microdevice that measures three-dimensional drug responses inside the body. The advance described in this work may enable superior imaging capabilities in clinical applications in which long and flexible imaging probes are favored.

This paper presents the complete development and experimental validation of a microsystem designed to systematically assess the impact of surface topography on cell adhesion and dynamics. The microsystem includes two pools for culturing cells and for including chemicals. These pools are connected by several channels that have different microtextures, along which the cells crawl from one well to another. The impact of channel surface topography on cell performance, as well as the influence of other relevant factors, can therefore be assessed. The microsystem stands out for its being able to precisely define the surface topographies from the design stage and also has the advantage of including the different textures under study in a single device. Validation has been carried out by culturing human mesenchymal stem cells (hMSCs) on the microsystem pre-treated with a coating of hMSC conditioned medium (CM) produced by these cells. The impact of surface topography on cell adhesion, motility, and velocity has been quantified, and the relevance of using a coating of hMSC-CM for these kinds of studies has been analyzed. Main results, current challenges, and future proposals based on the use of the proposed microsystem as an experimental resource for studying cell mechanobiology are also presented.

It is well known that neural activity can be modulated using a cooling device. The applications of this technique range from the treatment of medication-resistant cerebral diseases to brain functional mapping. Despite the potential benefits of such technique, its use has been limited due to the lack of suitable thermal modulators. This paper presents the design and validation of a solid-state cooler that was able to modulate the neural activity of rodents without the use of large and unpractical water pipes. A miniaturized thermal control solution based exclusively on solid-state devices was designed, occupying only 5 mm × 5 mm × 3 mm, and featuring the potential for wireless power and communications. The cold side of the device was cooled to 26 °C, while the hot side was kept below 43 °C. This range of temperatures is compatible with brain cooling and efficient enough for achieving some control of neural activity.

Approximately 26% of adult people, mostly females, are affected by varicose veins in old age. It is a common reason for distress, loss of efficiency, and worsening living conditions. Several traditional treatment techniques (sclerotherapy and foam sclerotherapy of large veins, laser surgeries and radiofrequency ablation, vein ligation and stripping, ambulatory phlebectomy, and endoscopic vein surgery) have failed to handle this disease effectively. Herein, authors have presented an alternative varicose vein implant method—the descending sinusoidal microchannel (DSMC). DSMC was simulated by Fuzzy logic MATLAB (The MathWorks, Natick, MA, USA) and ANSYS (ANSYS 18.2, perpetual license purchased by Ibadat Education Trust, The University of Lahore, Pakistan) with real and actual conditions. After simulations of DSMC, fabrication and testing were performed. The silver DSMC was manufactured by utilizing a micromachining procedure. The length, width, and depth of the silver substrate were 51 mm, 25 mm, and 1.1 mm, respectively. The measurements of the DSMC channel in the silver wafer substrate were 0.9 mm in width and 0.9 mm in depth. The three descending curves of the DSMC were 7 mm, 6 mm, and 5 mm in height. For pressure, actual conditions were carefully taken as 1.0 kPa to 1.5 kPa for varicose veins. For velocity, actual conditions were carefully taken as 0.02 m/s to 0.07 m/s for these veins. These are real and standard values used in simulations and experiments. At Reynolds number 323, the flow rate and velocity were determined as 1001.0 (0.1 nL/s), 11.4 cm/s and 1015.3 (0.1 nL/s), 12.19 cm/s by MATLAB (The MathWorks, Natick, MA, USA) and ANSYS simulations, respectively. The flow rate and velocity were determined to be 995.3 (0.1 nL/s) and 12.2 cm/s, respectively, at the same Reynolds number (323) in the experiment. Moreover, the Dean number was also calculated to observe Dean vortices. All simulated and experimental results were in close agreement. Consequently, DSMC can be implanted in varicose veins as a new treatment to preserve excellent blood flow in human legs from the original place to avoid tissue damage and other problems.

This paper presents an implantable microsystem for tonometric blood pressure measurement in small animals. The microsystem consists of four major components: (1) a titanium base for supporting a pressure sensor and an interface chip, (2) a micromachined capacitive pressure sensor array, (3) a switched-capacitor interface chip, and (4) a titanium cap. A new micromachining fabrication process has been developed to create capacitive pressure transducers with a flat surface necessary for tonometric pressure measurement. An array of three capacitive sensors is used to increase signal output and improve stability. A custom-designed switched-capacitor CMOS interface circuit is used to measure changes in capacitance. In vitro calibration tests have been performed on the complete cuff using a silastic tube to mimic a pliable blood vessel. A sensitivity of 2 mV/mmHg @ 100 mmHg and a resolution of 0.5 mmHg (based on 1 mV RMS interface chip noise floor) has been obtained. The dimensions of the cuff system 10(L)x6.5(W)x3(H) mm^3.