Tumor Mutational Burden (TMB) is a critical biomarker used to determine patient eligibility for immunotherapy with immune checkpoint inhibitors. However, its gold-standard assessment via whole exome sequencing is limited by high costs, technical complexity, and lengthy processing times. To address these challenges, we investigated whether Ultra-High-Frequency (UHF) electromagnetic wave sensing could serve as an alternative method for evaluating TMB. We analyzed the dielectrophoresis crossover frequency spectrum and corresponding electromagnetic signature (EMS) of cancer cells using a lab-on-a-chip biosensor that integrates microfluidics with dielectrophoresis-based electro-manipulation. Across seven solid tumor cell lines exhibiting diverse TMB levels, EMS exhibited an upward shift correlated with higher TMB, suggesting a relationship between mutational load and electromagnetic behavior. To further explore this connection, we artificially increased the somatic variant burden by exposing cells to the mutagen N-ethyl-N-nitrosourea (ENU). EMS measurements reliably detected the induced increase in variant load in ENU-treated cells. Overall, these findings demonstrate that EMS can detect both intrinsic TMB differences and experimentally induced increases in mutational burden, enabling refined categorization of cancer cells. Although further validation is required, this work lays the foundation for developing complementary, rapid, and accessible tools to support cancer cell stratification and guide immunotherapy decision-making.

Intracellular dielectric parameters are promising biomarkers, especially for specific cancerous subpopulations such as cancer stem cells. While valuable, these parameters remain challenging to extract, typically remaining complex microfluidic setups combined with inverse fitting computations. This paper introduces a simplified methodology based on a dual-mode dielectrophoretic measurement approach, integrated with a machine learning-based predictive pipeline, to extract intracellular dielectric parameters of cancerous cells cultured under standard versus stemness-promoting conditions. These parameters are then used to compute the Clausius-Mossotti factor in the ultra-high frequency range, enabling a comparative analysis of the dielectric responses between the two cellular phenotypes.

Cancer stem cells (CSCs) remain challenging to isolate and characterize because of their plastic phenotype. To overcome this issue, we used a microfluidic lab-on-a-chip analysis approach based on ultra-high frequency dielectophoresis (UHF-DEP) to measure the dielectrophoretic signature of colorectal cancer cells. We demonstrated that CSCs exhibit a distinct and lower frequency signature than differentiated cancer cells. Extracellular vesicles (EVs) released by tumor cells are implicated in tumor progression and metastasis. As CSC-derived EVs carry a more aggressive cargo, we hypothesized that treating differentiated colorectal cancer cells with these vesicles might affect their phenotype which would be detected by our lab on a chip. Indeed, the dielectrophoretic signature of cells treated with those EVs was altered in comparison to untreated cells, even in cases where no detectable biological changes were observed. Compared to conventional approaches using biomarkers to characterize CSCs, this UHF-DEP lab on a chip is a label-free method providing rapid and relevant results. Such a method could be useful in the clinic for the early detection of CSCs in the tumor mass, as well as for monitoring CSC-derived EVs in the bloodstream in order to study responses to therapy and prevent relapses.

This paper presents a biosensor architecture based on two injection locked oscillators (ILOs), implemented on a BiCMOS SiGe 130 nm process, dedicated to real time dielectric characterization of biological cells flowing at high speed within a microfluidic channel. The dielectric properties of biological cells and their intracellular content can be investigated thanks to the use of dielectric spectroscopy at microwave frequencies. Moreover, the ILOs are implemented with a capacitive transducer designed with two sensing areas of different sensitivity that makes possible the discrimination of distinct cells flowing at different elevations. Post-layout simulation results show that the system can achieve sensitivity levels that may enable the differentiation of two biological cells owning a relative dielectric permittivity difference of 1.

Tumor Mutational Burden (TMB) has emerged as a crucial biomarker that can increase patient eligibility for immunotherapy. However, accessibility to the gold-standard TMB measurement, whole exome sequencing, remains limited due to high costs, operational complexity, and lengthy processing times. To address these limitations, we investigated whether Ultra-High-Frequency (UHF) technology could serve as a novel approach to assess TMB by analyzing the crossover frequencies or electromagnetic signature (EMS) of cancer cells on a lab-on-a-chip biosensor, integrating microfluidics and dielectrophoresis. Using a panel of 12 cancer cell lines with varying TMB levels, we found that EMS demonstrated an upward shift in correlation with increasing TMB, especially in solid tumor cell lines, suggesting a potential relationship between TMB and EMS. To further explore this hypothesis, we artificially increased mutation levels by treating cells with the highly mutagenic compound N-ethyl-N-nitrosourea (ENU). Results showed that EMS captured significant TMB variations in ENU-treated cells with enhanced proliferative capacity compared to their parental counterparts. These results underscore the importance of matched control samples for reliable EMS measurements. Altogether, our findings highlight the potential of EMS to detect TMB variations associated with proliferative activity, a key hallmark of cancer cells, thereby enabling a more precise stratification of cancer cells. ### Competing Interest Statement The authors have declared no competing interest.

This article aims to investigate the Ultra-High Frequency Dielectrophoresis technique to characterize populations of human mesenchymal stem cells. The principle is based on studying the displacement of a cell in an electric field gradient to quantify a characteristic frequency that establishes the UHF dielectrophoretic 'signature' of the investigated cell population. Preliminary results obtained from patient-derived cultures, in correlation with conventional biological analyses, seem to indicate that the osteogenic differentiation of mesenchymal stem cells can be detected by UHF-DEP, making this technique an interesting approach to characterize hMSC differentiation in the context of optimizing bioceramics for bone regenerative medicine.

Cancer stem cells (CSCs) play a crucial role in tumor heterogeneity and the progression of colorectal cancer (CRC). However, identifying and isolating CSCs remains challenging, as conventional methods, such as fluorescent or magnetic labeling, are time-consuming and require substantial technical and biological resources, limiting their clinical applicability. In this study, we evaluated the potential application of a previously established approach with glioma cells, combining sedimentation field-flow fractionation (SdFFF) with a label-free Ultra-High Frequency dielectrophoresis (UHF-DEP) biosensor, for isolating and identifying CRC CSC. The integration of the UHF-DEP biosensor with SdFFF enables the identification of CSCs without specific labeling, simplifying their analysis. To optimize this coupling, we standardized the mobile phase between the two technologies. Producing two CSC sub-populations eluted in Fraction 1 and Fraction 3. For the first time, transcriptomic analysis was employed to deepen our understanding of the genetic composition of the cells, complementing functional and phenotypic characterizations. From these characteristics, it emerged that F1 cells corresponded to precursors, while F3 cells could be considered CSC. The UHF-DEP biosensor demonstrated its ability to detect these differences, linking F3 to cells cultivated in defined medium (DM), used as a reference standard. Finally, transcriptomic analysis (RNA-seq) has deepened our understanding of the genetic profiles of these subpopulations, enriching the interpretation of their characteristics as CSCs. This in-depth approach will also contribute to a better understanding of the results obtained by the UHF-DEP biosensor. ### Competing Interest Statement The authors have declared no competing interest.

This paper presents an integrated microfluidic cooling system for GaN transistors. This paper shows that it is possible to fabricate a compact cooling network, in the thickness of a MMIC GaN-on-Silicon substrate. In the proposed microstructure, the coolant is closer to the transistor and enables better heat extraction. In the proposed structure, the extracted heat flux is up to 280W.cm -2 for a pumping pressure of 200mbar. This setup will enable to dissipate more power in the component before reaching critical temperatures.

In this article, we introduce a method to exploit ultra-high dielectrophoresis (UHF-DEP) with a microfluidic radio frequency device able to sort biological cells by deflecting the trajectory of the targeted population in a continuous flow. This study highlights the capability of a high frequency lab-on-chip implemented UHF-DEP cytometer to isolate cancer stem cells (CSCs). Actually, CSCs sorting by an efficient, fast and low-cost method remains an issue. Above 20 MHz, the intracellular dielectric properties of cells determine the dielectrophoretic behavior of cells and is then very sensitive to the cell cytoplasm content. The proposed cell sorting principle exploits the combination of the fluidic drag and the repulsive dielectrophoretic forces in order to isolate CSCs hidden within differentiated cancer cells. We previously demonstrated the UHF-DEP behavior of cells, as a new type of electromagnetic biomarkers to discriminate cancer stem cells among a tumor population from colorectal cancer cell line.

A robust sensing mechanism requires a high sensitivity, fast response, and good fabrication compatibility. A surface acoustic wave (SAW) device possesses such properties, which make it suitable for gas sensing. This paper reported on the design, fabrication, characterization and measurement of a two-port SAW device built on an ST-cut quartz piezoelectric substrate. In order to develop a reliable SAW device, some performance parameters should be considered, such as the quality factor and electromechanical coupling coefficient. There are several possible ways to increase the quality factor of a SAW device such as by varying the number of interdigitated electrode (IDT) pairs as well as by using different IDT wavelengths. The devices were fabricated using three different numbers of IDTs $(\mathrm{N}=24,48$ , and 72) and two different IDT wavelengths $(\lambda=20\ \mu \mathrm{m}$ and 80 $\mu \mathrm{m})$ . The calculated quality factor, Q, confirmed that increasing the number of IDTs and reducing the value of the IDT wavelength would lead to a higher quality factor. The optimized SAW device with 72 IDTs and an IDT wavelength of 20 $\mu \mathrm{m}$ showed the highest quality factor of 306.58 at a resonance frequency of 248.33 MHz. The results of this study suggest that the ST-cut quartz SAW device with a high number of IDTs and small wavelength can be a better candidate for a surface acoustic wave device for sensing applications such as gas sensing.

Cancer stem cells remain a challenge to isolate and characterize because of their plastic phenotype. Using a microfluidic lab-on-a-chip based on ultra-high frequency dielectophoresis, we measured the electromagnetic signature of colorectal cancer cells and demonstrated that cancer stem cells show a distinct and lower electromagnetic signature than differentiated cells. The release of extracellular vesicles from tumor cells can drive tumor progression and metastasis development. As extracellular vesicles from cancer stem cells carry more aggressive content, we treated colorectal cancer cells with these vesicles to test whether the lab-on-a-chip can detect a change in phenotype. The electromagnetic signature of treated cells is modified in comparison to untreated cells and sometimes even when no biological change is observed. The lab-on-a-chip provides rapid and relevant result without prior labeling compared to conventional biological approaches. It could be useful in the clinic for early detection of cancer stem cells in the tumor mass and for monitoring the aggressive potential of extracellular vesicles in the bloodstream in order to adapt therapeutic management and prevent relapse.

This paper demonstrates the great potential of Ultra-High Frequency dielectrophoresis (UHF-DEP) to monitor the kinetics of glioblastoma (GBM) cells stemness phenotype transformation. Above 20 MHz, the method is able to probe the intracellular content and to be sensitive to its conductivity and permittivity values. U87-MG GBM cell line was cultured in different conditions in order to induce a differentiation gradient phenotype among the cell population. Using the presented characterization technic, it is shown than undifferentiated cells can be discriminated.

Nowadays, cancer stem cell (CSC) characterization with an efficient, fast and low-cost method still remains an issue. Hence, we have developed a microfluidic lab-on-chip RF sensor based on dielectrophoresis (DEP) to characterize individual biological cells by measuring their two crossover frequencies: f x01 (low frequency regime, below 1 MHz) and f x02 (Ultra High Frequency regime, above 50MHz). These electromagnetic signatures have been determined and compared between cancer stem cells and tumor differentiated cells from colorectal cancer cell line. We show that representative crossover frequency change appears in the UHF regime making such signatures a relevant biomarker to identify cancer stem cells among a tumor population.

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This paper presents the current progress towards a lab-on-chip biosensor for early dengue detection, consisting of an integrated sensor with dual-function working electrode that enables in-situ measurements of both electrochemical impedance spectroscopy (EIS) and quartz crystal microbalance (QCM) enclosed in a miniaturized 3D-printed package equipped with electrical contacts and sample fluid delivery to the quartz biosensor array. The sensors consist of an array of three 10 MI-lz IEQCM biosensors on a single quartz substrate. Early validation is performed for future dengue sensing application. We report the design, optimisation, and fabrication of the sensors, as well as early optimisation and validation of surface bioconjugation of antibodies. This lab-on-chip has the potential to provide accurate dengue detection due to its high sensitivity and dynamic range, as well as providing rapid and early dengue detection in point-of-care settings.

This paper presents a microfluidic radiofrequency device operating at a few hundred MHz, which is able to sort biological cells. It uses a non-invasive and label-free technic based on intracellular dielectric specificities of biological cells. The sorting principle relies on a dynamic dielectrophoresis (DEP) deviation resulting from the interaction between a high frequency electric signal and the cell cytoplasm content. Driven in a microfluidic channel by a continuous flow, cells are individually deflected from their primary trajectories after having entered a non-uniform electric field generated by a microelectrode system. Designed with different slopes, these electrodes allow a selective guiding of cells to different outlets depending on the dielectrophoresis deviation efficiency. To allow a successful cell sorting, the intensity of deviation forces acting on cells is modulated according to the particle speed, the dielectrophoresis signal frequency and the electrode slope angles related to the Clausius-Mossotti factor of each cell. As proof of concept, experiments with cells from glioblastoma line were carried out, using different DEP signal frequencies to highlight system ability to sort cells from heterogeneous basal population into less disparate sub-populations.

Diabetes has become a major health problem in society. Invasive glucometers, although precise, only provide discrete measurements at specific times and are unsuitable for long-term monitoring due to the injuries caused on skin and the prohibitive cost of disposables. Remote, continuous, self-monitoring of blood sugar levels allows for active and better management of diabetics. In this work, we present a radio frequency (RF) sensor based on a stepped impedance resonator for remote blood glucose monitoring. When placed on top of a human hand, this RF interdigital sensor allows detection of variation in blood sugar levels by monitoring the changes in the dielectric constant of the material underneath. The designed stepped impedance resonator operates at 3.528 GHz with a Q factor of 1455. A microfluidic device structure that imitates the blood veins in the human hand was fabricated in PDMS to validate that the sensor can measure changes in glucose concentrations. To test the RF sensor, glucose solutions with concentrations ranging from 0 to 240 mg/dL were injected into the fluidic channels and placed underneath the RF sensor. The shifts in the resonance frequencies of the RF sensor were measured using a network analyzer via its S11 parameters. Based on the change in resonance frequencies, the sensitivity of the biosensor was found to be 264.2 kHz/mg·dL−1 and its LOD was calculated to be 29.89 mg/dL.

Cancer stem cells (CSCs) appear to be an essential target for cancer therapies, in particular, in brain tumors such as Glioblastoma. Nevertheless, their isolation is made difficult by their low content in culture or tumors (<5% of the tumor mass) and is essentially based on the use of fluorescent or magnetic labeling techniques, increasing the risk of differentiation induction. The use of label-free separation methods such as sedimentation field-flow fractionation (SdFFF) is promising, but it becomes necessary to consider a coupling with a detection and characterization method for future identification and purification of CSCs from patient-derived tumors. In this study, we demonstrate for the first time the capability of using an ultrahigh-frequency range dielectrophoresis fluidic biosensor as a detector. This implies an important methodological adaptation of SdFFF cell sorting by the use of a new compatible carrier liquid DEP buffer (DEP-B). After SdFFF sorting, subpopulations derived from U87-MG and LN18 cell lines undergo biological characterization, demonstrating that using DEP-B as a carrier liquid, we sorted by SdFFF subpopulations with specific differentiation characteristics: F1 = differentiated cells/F2 = CSCs. These subpopulations presented high-frequency crossover (HFC) values similar to those measured for standard differentiated (around 110 MHz) and CSC (around 80 MHz) populations. This coupling appeared as a promising solution for the development of an online integration of these two complementary label-free separation/detection technologies.

This paper introduces results about characterizations of different tumor cell lines, using intracellular sensing based on Ultra High Frequency dielectrophoresis (UHF-DEP). Above 50 MHz, presented technic allows to probe internal cell content to characterize its cytoplasm permittivity and conductivity properties. The measured frequency-dependent cell behavior results on a distinctive DEP signature according to the cell type and its biological specificity. This paper illustrates the high potential of UHF lab-on-chip sensor to discriminate various tumor cell types derived from different tissues.

Glioblastoma (GBM) is one of the most aggressive solid tumors, particularly due to the presence of cancer stem cells (CSCs). Nowadays, the characterization of this cell type with an efficient, fast and low-cost method remains an issue. Hence, we have developed a microfluidic lab-on-a-chip based on dielectrophoresis (DEP) single cell electro-manipulation to measure the two crossover frequencies: fx01 in the low-frequency range (below 500 kHz) and fx02 in the ultra-high-frequency range (UHF, above 50 MHz). First, in vitro conditions were investigated. An U87-MG cell line was cultured in different conditions in order to induce an undifferentiated phenotype. Then, ex vivo GBM cells from patients' primary cell culture were passed through the developed microfluidic system and characterized in order to reflect clinical conditions. This article demonstrates that the usual exploitation of low-frequency range DEP does not allow the discrimination of the undifferentiated GBM cells from the differentiated one. However, the presented study highlights the use of UHF-DEP as a relevant discriminant parameter. The proposed microfluidic lab-on-a-chip is able to follow the kinetics of U87-MG phenotype transformation in a CSC enrichment medium and the cancer stem cells phenotype acquirement.