Search Results (644)

The development of bionic organ-on-a-chip technology relies heavily on advancements in in situ sensors and biochip packaging. By integrating precise biological and fluid condition sensing with microfluidics and electronic components, long-term dynamic closed-loop culture systems can be achieved. This study aims to develop biocompatible heterogeneous packaging and laser surface modification techniques to enable the encapsulation of electronic components while minimizing their impact on fluid dynamics. Using a kidney-on-a-chip as a case study, a non-toxic packaging process and fluid interface control methods have been successfully developed. Experimentally, miniature pressure sensors and control circuit boards were encapsulated using parylene-C, a biocompatible material, to isolate biochemical fluids from electronic components. Ultraviolet laser processing was employed to fabricate structures on parylene-C. The results demonstrate that through precise control of processing parameters, the wettability of the material can be tuned freely within a contact angle range of 60° to 110°. Morphological observations and MTT assays confirmed that the material and the processing methods do not induce cytotoxicity. This technology will facilitate the packaging of various miniature electronic components and biochips in the future. Furthermore, laser processing enables rapid and precise control of interface conditions across different regions within the chip, demonstrating a high potential for customized mass production of biochips. The proposed innovations provide a solution for in situ sensing in organ-on-a-chip systems and advanced biochip packaging. We believe that the development of this technology is a critical step toward realizing the concept of “organ twin”. Full article

Lung cancer is the most common type of cancer diagnosed worldwide and is also among the most fatal. Early detection, before symptoms become evident, is fundamental for patients’ survival. Therefore, several lung cancer biomarkers have been proposed to enable a prompt diagnosis, including neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA). NSE and CEA are two serum proteins whose elevated levels have been associated with lung cancer. Hence, in this study, impedimetric biosensors (immunosensors) able to quantify NSE and CEA were developed as proof-of-concept devices for lung cancer diagnosis. The sensing platform exploited for the immunosensors comprises a novel combination of a magnetic platform, screen-printed gold electrode (SPGE), and magnetic nanobeads (MB). The MB were functionalized with antibodies to capture the analyte from the sample and to move it over the sensing area. The immunosensors were then developed by immobilizing another set of antibodies for either CEA or NSE on the SPGE through formation of self-assembled monolayer (SAM). The second set of antibodies enabled a sandwich assay to be formed on the surface of the sensor, while MB manipulation was applied during the sensor performance to depict a microfluidic system and increase antigen–antibody complex formation prior to CEA or NSE detection and quantification. The optimized immunosensors were successfully tested to measure various concentrations of CEA and NSE (0–100 ng/mL) in both phosphate buffer and 100% human serum samples. Clinically relevant detection limits of 0.26 ng/mL and 0.18 ng/mL in buffer and 0.76 ng/mL and 0.52 ng/mL in 100% serum for CEA and NSE, respectively, were achieved via electrochemical impedance spectroscopy with the use of potassium ferri/ferrocyanide as a redox probe. Hence, the two immunosensors demonstrated great potential as tools to be implemented for the early detection of lung cancer. Full article

This paper introduces a Coriolis mass flow and density sensor. The sensor is made using Surface Channel Technology (SCT) but with selective wet etching to create the channels. This method forms suspended microfluidic channels with a larger cross-sectional area. Because of this larger cross-sectional area, the sensor has a much higher flow range, up to 50 g h−1 (for water) with a pressure drop of 1 bar, compared to the standard SCT-based Coriolis sensor, which is only 1.2 g h−1. The channel has a semi-elliptical cross-sectional area, measuring 200 micrometers wide and 70 micrometers deep. The channel wall is made of a stack of thin films with a total thickness of 2.5 μm. Water, isopropyl alcohol (IPA), and nitrogen (N₂) are used to test and evaluate the sensor’s mass flow and density sensing performance. Full article

This paper reviews microwave sensors and their applications in permittivity measurement. The detection, diagnosis, classification, and monitoring without contact and invasion have been the subject of numerous studies based on permittivity characteristics tracking. This review illustrates many new types of research in recent years. Firstly, the application background is briefly introduced, and several main measurement methods are presented. An overview of measurement technology in various applications is compiled and summarized based on numerous typical examples. Exciting applications are compared and presented separately, combining resonator sensors with strong electric fields. Furthermore, differential signals represent trends for future applications with strong environmental immunity, an alternative option to expensive measuring equipment. With the alternation of metamaterials, microfluidics technologies, cross-technology, algorithms, and so on, sensors play an exceptionally prominent role in practical and low-cost applications. Full article

The detection and analysis of cancer cell exosomes with high sensitivity and precision are pivotal for the early diagnosis and treatment strategies of prostate cancer. To this end, a microfluidic chip, equipped with a cactus-like array substrate (CAS) based on surface-enhanced Raman spectroscopy (SERS) was designed and fabricated for the detection of exosome concentrations in Lymph Node Carcinoma of the Prostate (LNCaP). Double layers of polystyrene (PS) microspheres were self-assembled onto a polyethylene terephthalate (PET) film to form an ordered cactus-like nanoarray for detection and analysis. By combining EpCAM aptamer-labeled SERS nanoprobes and a CD63 aptamer-labeled CAS, a ‘sandwich’ structure was formed and applied to the microfluidic chips, further enhancing the Raman scattering signal of Raman reporter molecules. The results indicate that the integrated microfluidic sensor exhibits a good linear response within the detection concentration range of 10⁵ particles μL⁻¹ to 1 particle μL⁻¹. The detection limit of exosomes in cancer cells can reach 1 particle μL⁻¹. Therefore, we believed that the CAS integrated microfluidic sensor offers a superior solution for the early diagnosis and therapeutic intervention of prostate cancer. Full article

This review examines recent advances in surface-enhanced Raman spectroscopy (SERS) for urinary metabolite analysis, focusing on the development and application of noble metal nanohybrids. We explore the diverse range of hybrid materials, including carbon-based, metal–organic-framework (MOF), silicon-based, semiconductor, and polymer-based systems, which have significantly improved SERS performance for detecting key urinary biomarkers. The principles underlying SERS enhancement in these nanohybrids are discussed, elucidating both electromagnetic and chemical enhancement mechanisms. We analyze various fabrication methods that enable precise control over nanostructure morphology, composition, and surface chemistry. The review critically evaluates the analytical performance of different hybrid systems for detecting specific urinary metabolites, considering factors such as sensitivity, selectivity, and stability. We address the analytical challenges associated with SERS-based urinary metabolite analysis, including sample preparation, matrix effects, and data interpretation. Innovative solutions, such as the integration of SERS with microfluidic devices and the application of machine learning algorithms for spectral analysis, are highlighted. The potential of these advanced SERS platforms for point-of-care diagnostics and personalized medicine is discussed, along with future perspectives on wearable SERS sensors and multi-modal analysis techniques. This comprehensive overview provides insights into the current state and future directions of SERS technology for urinary metabolite detection, emphasizing its potential to revolutionize non-invasive health monitoring and disease diagnosis. Full article

Despite major advances in the field of actuator technology for microsystems, miniaturized microfluidic actuation systems for mobile devices are still not common in the market. We present a micropump concept and an associated mass flow sensor design, which, in combination, have the potential to form the basis for an integrated microfluidic development platform for microfluidic systems in general and microdosing systems in particular. The micropump combines the use of active valves with an electrostatic drive principle for the pump membrane and the valves, respectively. With a size of only 1.86 mm × 1.86 mm × 0.3 mm, the first prototypes are capable of pumping gaseous media at flow rates of up to 110 μL/min. A specific feature of the presented micropump is that the pumping direction is perpendicular to the chip surface. The corresponding flow sensor combines the principle of hot-wire anemometry with a very small footprint of only 1.4 mm × 1.4 mm × 0.4 mm. The main innovation is that the hot wires are fixed inside a through-hole in the substrate of the microchip, so that the flow direction of the fluid to be measured is perpendicular to the chip surface, which enables direct integration with the presented micropump. Detection thresholds of around 10 μL/min and measuring ranges of up to 20 mL/min can be achieved with the first prototypes, without dedicated evaluation electronics. Full article

A new instrument for label-free measurements based on optical Low-Q Whispering Gallery Modes (WGMs) for various applications is used for a detailed study of the deposition and release of Layer-by-Layer polymer coatings. The two selected coating pairs interact either via hydrogen bonding or electrostatic interactions. Their assembly was followed by common Quartz Crystal Microbalance (QCM) technology and the Low-Q WGMs. In contrast to planar QCM sensor chips of 1 cm, the WGM sensors are fluorescent spherical beads with diameters of 10.2 µm, enabling the detection of analyte quantities in the femtogram range in tiny volumes. The beads, with a very smooth surface and high refractive index, act as resonators for circular light waves that can revolve up to 10,000 times within the bead. The WGM frequencies are highly sensitive to changes in particle diameter and the refractive index of the surrounding medium. Hence, the adsorption of molecules shifts the resonance frequency, which is detected by a robust instrument with a high-resolution spectrometer. The results demonstrate the high potential of the new photonic measurement and its advantages over QCM technology, such as cheap sensors (billions in one Eppendorf tube), simple pre-functionalization, much higher statistic safety by hundreds of sensors for one measurement, 5–10 times faster analysis, and that approx. 25, 000 fewer analyte molecules are needed for one sensor. In addition, the deposited molecule amount is not superposed by hydrated water as for QCM. A connection between sensors and instruments does not exist, enabling application in any transparent environment, like microfluidics, drop-on slides, Petri dishes, well plates, cell culture vasculature, etc. Full article

We investigated the design and characterization of a Lab-On-a-Chip (LoC) cell detection system primarily designed to support immunotherapy in cancer treatment. Immunotherapy uses Chimeric Antigen Receptors (CARs) and T Cell Receptors (TCRs) to fight cancer, engineering the response of the immune system. In recent years, it has emerged as a promising strategy for personalized cancer treatment. However, it requires bioreactor-based cell culture expansion and manual quality control (QC) of the modified cells, which is time-consuming, labour-intensive, and prone to errors. The miniaturized LoC device for automated QC demonstrated here is simple, has a low cost, and is reliable. Its final target is to become one of the building blocks of an LoC for immunotherapy, which would take the place of present labs and manual procedures to the benefit of throughput and affordability. The core of the system is a commercial, on-chip-integrated capacitive sensor managed by a microcontroller capable of sensing cells as accurately measured charge variations. The hardware is based on standardized components, which makes it suitable for mass manufacturing. Moreover, unlike in other cell detection solutions, no external AC source is required. The device has been characterized with a cell line model selectively labelled with gold nanoparticles to simulate its future use in bioreactors in which labelling can apply to successfully engineered CAR-T-cells. Experiments were run both in the air—free drop with no microfluidics—and in the channel, where the fluid volume was considerably lower than in the drop. The device showed good sensitivity even with a low number of cells—around 120, compared with the 10⁷ to 10⁸ needed per kilogram of body weight—which is desirable for a good outcome of the expansion process. Since cell detection is needed in several contexts other than immunotherapy, the usefulness of this LoC goes potentially beyond the scope considered here. Full article

Sweat rate magnitude is a desired outcome for any wearable sensing patch dedicated to sweat analysis. Indeed, sweat rate values can be used two-fold: self-diagnosis of dehydration and correction/normalization of other physiological metrics, such as Borg scale, VO2, and different chemical species concentrations. Herein, a reliable sweat rate belt device for sweat rate monitoring was developed. The device measures sweat rates in the range from 1.0 to 5.0 µL min⁻¹ (2 to 10 µL min⁻¹ cm⁻²), which covers typical values for humans. The working mechanism is based on a new direct current (DC) step protocol activating a series of differential resistance measurements (spatially separated by 800 µm) that is gradually initiated by the action of sweat, which flows along a customized microfluidic track (~600 µm in width, 10 mm in length, and 235 µm in thickness). The device has a volumetric capacity of ~16 µL and an acquisition frequency between 0.010 and 0.043 Hz within the measured sweat rate range. Importantly, instead of using a typical and rather complex AC signal interrogation and acquisition, we put forward the DC approach, offering several benefits, such as simplified circuit design for easier fabrication and lower costs, as well as reduced power consumption and suitability for wearable applications. For the validation, either the commercial sweat collector (colorimetric) or the developed device was performed. In five on-body tests, an acceptable variation of ca. 10% was obtained. Overall, this study demonstrates the potential of the DC-based device for the monitoring of sweat rate and also its potential for implementation in any wearable sweat platform. Full article

Loop-Mediated Isothermal Loop-Mediated Isothermal Amplification (LAMP) is a widely used technique for nucleic acid amplification due to its high specificity, sensitivity, and rapid results. Advances in microfluidic lab-on-chip (LOC) technology have enabled the integration of LAMP into miniaturized devices, known as μ-LAMP, which require precise thermal control for optimal DNA amplification. This paper introduces a novel thermal bed design using PCB copper traces and FR−4 dielectric materials, providing a reliable, modular, and repairable heating platform. The system achieves accurate and stable temperature control, which is critical for μ-LAMP applications, with temperature deviations within ±1.0 °C. The thermal bed’s performance is validated through finite element method (FEM) simulations, showing uniform temperature distribution and a rapid thermal response of 2.5 s to reach the target temperature. These results highlight the system’s potential for applications such as disease diagnostics, biological safety, and forensic analysis, where precision and reliability are paramount. Full article

In this study, we developed an optofluidic chip consisting of a guided-mode resonance (GMR) sensor incorporated into a microfluidic chip to achieve simultaneous blood plasma separation and label-free albumin detection. A sedimentation chamber is integrated into the microfluidic chip to achieve plasma separation through differences in density. After a blood sample is loaded into the optofluidic chip in two stages with controlled flow rates, the blood cells are kept in the sedimentation chamber, enabling only the plasma to reach the GMR sensor for albumin detection. This GMR sensor, fabricated using plastic replica molding, achieved a bulk sensitivity of 175.66 nm/RIU. With surface-bound antibodies, the GMR sensor exhibited a limit of detection of 0.16 μg/mL for recombinant albumin in buffer solution. Overall, our findings demonstrate the potential of our integrated chip for use in clinical samples for biomarker detection in point-of-care applications. Full article

The small dimensions of microfluidic channels allow for fast diffusive or passive mixing, which is beneficial for time-sensitive applications such as chemical reactions, biological assays, and the transport of to-be-detected species to sensors. In microfluidics, the need for fast mixing within milliseconds arises primarily because these devices are often used in fields where rapid and efficient mixing significantly impacts the performance and outcome of the processes. Active mixing with acoustics in microfluidic devices involves using acoustic waves to enhance the mixing of fluids within microchannels. Using sharp corners and wall patterns in acoustofluidic devices significantly enhances the mixing by acoustic streaming around these features. The streaming patterns around the sharp edges are particularly effective for the mixing because they can produce strong lateral flows that rapidly homogenize liquids. This work presents extensive characterizations of the effect of sharp-edged structures on acoustic mixing in bulk acoustic wave (BAW) mode in a silicon microdevice. The effect of side wall patterns in different angles and shapes, their positions, the type of piezoelectric transducer, and its amplitude and frequency have been studied. Following the patterning of the channel walls, a mixing time of 25 times faster was reached, compared to channels with smooth side walls exhibiting conventional BAW behavior. The average locally determined acoustic streaming velocity inside the channel becomes 14 times faster if sharp corners of 10° are added to the wall. Full article

In this paper, which represents a fundamental step in ongoing research, a new smart low-energy dual-function half-mode substrate integrated waveguide cavity-interdigital capacitor (HMSIWC-DIC) antenna-based sensor is developed and investigated for remote frost and wildfire detection applications at 5.7 GHz. The proposed methodology exploits the HMSIW antenna-based sensor, a microfluidic channel (microliter water channel (50 μL)), interdigital capacitor technologies, and the resonance frequency parameters combined with machine learning algorithms. This allows for superior interaction between the water channel and the TE101 mode, resulting in high sensitivity (∆f/∆ε = 5.5 MHz/ε (F/m) and ∆f/∆°C = 1.83 MHz/°C) within the sensing range. Additionally, it exhibits high decision-making ability and immunity to interference, demonstrating a best-in-class sensory response to weather temperature across two ranges: positive (≥0 °C, including frost and wildfire) and negative (<0 °C, including ice accumulation). To address the challenges posed by the non-linear, unpredictable behavior of resonance frequency results, even when dealing with weak sensor antenna responses, an innovative sensory intelligent system was proposed. This system utilizes resonance frequency results as features to classify and predict weather temperature ranges into three environmental states: Early Frost, Normal, and Early Wildfire, achieving an accuracy of 96.4%. Several machine learning techniques are employed, including artificial neural networks (ANNs), random forests (RF), decision trees (DT), support vector machines (SVMs), and Gaussian processes (GPs). This sensor serves as an ideal solution for energy management through its utilization in RF-based weather temperature sensing applications. It boasts stable performance, minimal energy consumption, and real-time sensitivity, eliminating the necessity for manual data recording. Full article

Recently, there has been a huge increase in the different ways to manufacture polymer-based sensors. Methods like additive manufacturing, microfluidic preparation, and brush painting are just a few examples of new approaches designed to improve sensor features like self-healing, higher sensitivity, reduced drift over time, and lower hysteresis. That being said, we believe there is still a lot of potential to boost the performance of current sensors by applying modeling, classification, and machine learning techniques. With this approach, final sensor users may benefit from inexpensive computational methods instead of dealing with the already mentioned manufacturing routes. In this study, a total of 96 specimens of two commercial brands of Force Sensing Resistors (FSRs) were characterized under the error metrics of drift and hysteresis; the characterization was performed at multiple input voltages in a tailored test bench. It was found that the output voltage at null force (V_{o_null}) of a given specimen is inversely correlated with its drift error, and, consequently, it is possible to predict the sensor’s performance by performing inexpensive electrical measurements on the sensor before deploying it to the final application. Hysteresis error was also studied in regard to V_{o_null} readings; nonetheless, a relationship between V_{o_null} and hysteresis was not found. However, a classification rule base on k-means clustering method was implemented; the clustering allowed us to distinguish in advance between sensors with high and low hysteresis by relying solely on V_{o_null} readings; the method was successfully implemented on Peratech SP200 sensors, but it could be applied to Interlink FSR402 sensors. With the aim of providing a comprehensive insight of the experimental data, the theoretical foundations of FSRs are also presented and correlated with the introduced modeling/classification techniques. Full article