Lithium is the first-line treatment for bipolar disorder. However, the narrow therapeutic window of serum (s-)lithium is near its toxicity range, necessitating continuous monitoring of patients, a process involving regular hospital visits. On-demand home sampling could allow for more frequent testing, possibly resulting in safer patient outcomes, further dosage optimization, and increased compliance. This article presents a device that measures the s-lithium concentration from whole blood. The device consists of a single-use cartridge able to conduct on-chip serum filtration, volume-metering and an on-chip colorimetric assay. Spiked whole blood shows good linearity (Pearson's r = 0.96, R2 = 0.92), a limit-of-detection of 0.3 mmol L-1, and an average deviation of 0.05 mmol L-1 (+/- 6%) compared to atomic absorption spectroscopy. The on-chip colorimetric assay has shown to be a promising technique for measuring s-lithium concentration from whole blood and could allow patients to assess lithium levels at home and make the treatment available for new patient groups.

Smart agriculture and environmental monitoring claim innovative wearable sensing technologies suitable for real-time, in-situ biochemical analysis for non-specialized users in plants. Current strategies measure physical parameters, ions or hormones by amperometry or potentiometry. Among these, plant hormones serve as stress biomarkers due to their role in stress response mechanisms. While electrocatalysis has been explored for their detection, early-stage stress monitoring at low concentrations demands higher selectivity and specificity. Therefore, new strategies integrating biorecognition elements, such as antibodies, with autonomous sample collection and bioassay performance are required. In this regard, this work proposes a novel wearable immunosensor device based on an electrochemical lateral flow assay (eLF) that includes an autonomous microsampling technology for minimally invasive in-situ sap extraction and abscisic acid (ABA) detection. This sap device collects, processes and analyzes plant sap with low sample volume (<10 μL) and short assay time (9min) using immunosensing for the first time in ABA wearable detection. Validation in drought-stressed cucumber plants demonstrated 78 % sensitivity and 71 % specificity in detecting subtle water stress with 77 % accuracy. These findings highlight the potential of this plant-wearable biosensor for early stress detection and its versatility to be adapted for the detection of other relevant molecules (proteins or DNA), key for smart agriculture and environmental monitoring.

Blood sampling is a common practice to monitor health, but it entails a series of drawbacks for patients including pain and discomfort. Thus, there is a demand for more convenient ways to obtain samples. Modern analytical techniques enable monitoring of multiple bioanalytes in smaller samples, opening possibilities for new matrices, and microsampling technologies to be adopted. Interstitial fluid (ISF) is an attractive alternative matrix that shows good correlation with plasma concentration dynamics for several analytes and can be sampled in a minimally invasive and painless manner from the skin at the point-of-care. However, there is currently a lack of sampling devices compatible with clinical translation. Here, to tackle state-of-the-art limitations, a cost-effective and compact single-microneedle-based device designed to painlessly collect precisely 1.1 µL of dermal ISF within minutes is presented. The fluid is volume-metered, dried, and stably stored into analytical-grade paper within the microfluidic device. The obtained sample can be mailed to a laboratory, quantitatively analyzed, and provide molecular insights comparable to blood testing. In a human study, the possibility to monitor various classes of molecular analytes is demonstrated in ISF microsamples, including caffeine, hundreds of proteins, and SARS-CoV-2 antibodies, some being detected in ISF for the first time.

Interdisciplinary research between medicine and microsystem engineering creates new possibilities to improve the quality of life of patients or to further enhance the performance of already existing devices. In particular, microsystems show great potential for the realization of biosensors and sampling devices to monitor bioanalytes with minimal patient discomfort. Microneedles offer a minimally invasive and painless solution to penetrate the epidermis and provide access to dermal interstitial fluid (ISF), to monitor various substances without the need for more invasive and painful extraction of blood. Diabetes, for example, requires continuous monitoring of the glucose levels in the body (CGM) to avoid complications. Although glucose is traditionally measured in finger-prick blood, CGM, which is performed in ISF, has been proven to be beneficial in the management of the disease. However, current commercial solutions are still relatively large and invasive. In this work, an electrochemical glucose sensor 50 times smaller than competing commercial devices was combined with a hollow silicon microneedle and shown to be able to measure glucose levels in the dermis in vivo. A scalable manufacturing method for the assembly of the two separately fabricated components and their electrical interconnection was also demonstrated. At the same time, a single data point may be sufficient in other situations, such as when only the presence of a certain biomarker or drug needs to be assessed. Although continuous monitoring is not required in these cases, the patient would still benefit by avoiding blood extraction. However, there are no simple devices currently available to reliably sample and store ISF. A painless microneedle-based sampling device designed to extract 1 μL of ISF from the dermis was realized. The sampled liquid is metered and stored in a paper matrix embedded in a microfluidic chip. The sample could then be analyzed using state-of-the-art tools, such as mass spectrometry.On the other hand, device miniaturization also creates issues for sensor performance. In certain types of electrochemical gas sensors, such as nitric oxide sensors used for asthma monitoring, the reduced size results in a shorter device lifetime. These sensors typically operate with a liquid electrolyte, subject to evaporation, and their long-term stability tends to be proportional to the electrode size. To address this issue, a gas diffusion and evaporation controlling platform to be integrated with this type of sensors was proposed. Such a platform opens or seals the sensing compartment on demand, potentially enabling sensor recalibration and evaporation reduction when the sensor is not in use. The device is based on electrowetting-on-dielectric actuation of low-vapor-pressure ionic liquid microdroplets on partially perforated membranes. The platform was then modified to create a zero-insertion loss and broad-band-operation laser shutter.

The out-of-plane integration of microfabricated planar microchips into functional three-dimensional (3D) devices is a challenge in various emerging MEMS applications such as advanced biosensors and flow sensors. However, no conventional approach currently provides a versatile solution to vertically assemble sensitive or fragile microchips into a separate receiving substrate and to create electrical connections. In this study, we present a method to realize vertical magnetic-field-assisted assembly of discrete silicon microchips into a target receiving substrate and subsequent electrical contacting of the microchips by edge wire bonding, to create interconnections between the receiving substrate and the vertically oriented microchips. Vertical assembly is achieved by combining carefully designed microchip geometries for shape matching and striped patterns of the ferromagnetic material (nickel) on the backside of the microchips, enabling controlled vertical lifting directionality independently of the microchip's aspect ratio. To form electrical connections between the receiving substrate and a vertically assembled microchip, featuring standard metallic contact electrodes only on its frontside, an edge wire bonding process was developed to realize ball bonds on the top sidewall of the vertically placed microchip. The top sidewall features silicon trenches in correspondence to the frontside electrodes, which induce deformation of the free air balls and result in both mechanical ball bond fixation and around-the-edge metallic connections. The edge wire bonds are realized at room temperature and show minimal contact resistance (<0.2 Omega) and excellent mechanical robustness (>168mN in pull tests). In our approach, the microchips and the receiving substrate are independently manufactured using standard silicon micromachining processes and materials, with a subsequent heterogeneous integration of the components. Thus, this integration technology potentially enables emerging MEMS applications that require 3D out-of-plane assembly of microchips.

This article reports a broad-band optical shutter based on microdroplet actuation with zero optical insertion loss in the open state. These features are achieved by electrowetting-on-dielectric (EWOD) actuation of opaque ionic liquid microdroplets. The negligible vapor pressure of ionic liquids allows the device to robustly operate in open air, unlike previously proposed EWOD-based systems in which the light crosses several attenuating and reflective layers, preventing broad-band operation and creating insertion losses > 14%. The presented device provides an attenuation of 78dB in the closed state and a transmission of >99.99999% in the open state and can operate in the visible and mid-infrared wavelength range. Moreover, the switch can sustain larger incoming laser powers (5 mW continuous exposure or up to 3h of continuous exposure at similar to 100mW) compared to the values reported for other state-of-the-art EWOD-based shutters. Additionally, the proposed device is compact, operates with low voltage (<25V peak voltage), and features zero static power consumption.

This paper reports the first optical shutter based on electrical actuation of microdroplets featuring zero insertion loss in the open state and broad-band operation. These features are achieved by electrowetting-on-dielectric (EWOD) actuation of ionic liquid microdroplets. Due to their negligible vapor pressure, ionic liquids allow the switch to robustly operate in air, unlike previously proposed systems in which the light had to cross several attenuating and refractive layers. Moreover, this solution enables operation in a much wider wavelength range, e.g. in the infrared spectrum where glass has strong absorption. Additionally, the proposed device requires lower voltage to operate (25 V) and features zero static power consumption.

The lifetime of electrochemical gas sensors suffers from electrolyte evaporation and from the impracticality to perform recalibration. To tackle these issues, a prototype of a microfabricated gas diffusion controlling system, based on coplanar electrowetting-on-dielectric (EWOD) actuation of ionic liquid microdroplets, is presented. The system is designed to be integrated with electrochemical gas sensors to allow on-demand sealing of the sensing chamber from the environment. The MEMS device can be electrically toggled between an open and a closed state, in which the microdroplets are used to cover or uncover the openings of a perforated membrane connecting to the sensing compartment, respectively. This ON/OFF diffusion-blocking valve mechanism potentially allows for recalibration and for liquid electrolyte evaporation reduction when the sensor is not in use, thus extending the gas sensor lifetime. A one order of magnitude reduction of evaporation rate and a more than three orders of magnitude reduction of gas diffusion time were experimentally demonstrated. Ionic liquid movement can be performed with an applied AC voltage as low as 18 V, using super-hydrophobic cover plates to facilitate droplet motion. Furthermore, the shown ionic liquid micro-droplet manipulation provides a robust and low voltage platform for digital microfluidics, readily adaptable to serve different applications.

Encapsulation of therapeutic cells in core-shell microparticles has great promise for the treatment of a range of health conditions. Unresolved challenges related to control of the particle morphology, mechanical stability, and immunogenicity hinder dissemination of this promising approach. Here, a novel polymer material for cell encapsulation and a combined novel, easy to control, synthesis method are introduced. Core-shell cell encapsulation is demonstrated with a concentric core-shell morphology formed during a single UV exposure, resulting in particles that consist of a synthetic hydrogel core of polyethylene glycol diacrylate and a solid, but porous, shell of off-stoichiometric thiol-ene. The encapsulated human cells in 100 mu m diameter particles have >90% viability. The average shell thickness is controlled between 7 and 13 mu m by varying the UV exposure, and the shell is measured to be permeable to low molecular weight species (<180 Da) but impermeable to higher molecular weight species (>480 Da). The unique material properties and the orthogonal control of the microparticle core size, shell thickness, shell permeability, and shell surface properties address the key unresolved challenges in the field, and are expected to enable faster translation of novel cell therapy concepts from research to clinical practice.

This article presents a proof-of-concept of a device able to control (ON/OFF) gas diffusion through a perforated membrane. The microfabricated system is based on electrowetting-on-dielectric (EWOD) actuation of ionic liquid (IL) microdroplets and can be electrically toggled from an open to a closed state, in which microdroplets cover or uncover the membrane openings, respectively. The system is designed to be integrated with liquid-electrolyte-based electrochemical gas sensors, to extend their lifetime by reducing electrolyte evaporation and allowing recalibration. The realized device was proven to limit gas diffusion and water evaporation through perforated portions of thin membranes on command.