| 1. |
- Ribet, Federico, et al.
(författare)
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Gas diffusion and evaporation control using EWOD actuation of ionic liquid microdroplets for gas sensing applications
- 2018
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Ingår i: Sensors and actuators. B, Chemical. - : Elsevier. - 0925-4005 .- 1873-3077. ; 267, s. 647-654
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Ribet, Federico
(författare)
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Integrated microsystems for continuous glucose monitoring, interstitial fluid sampling and digital microfluidics
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 3. |
- Ribet, Federico, et al.
(författare)
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Ionic liquid microdroplet manipulation by electrowetting-on-dielectric for on/off diffusion control
- 2018
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Ingår i: 2018 IEEE Micro Electro Mechanical Systems (MEMS). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538647820 ; , s. 1181-1184
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Konferensbidrag (refereegranskat)abstract
- 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.
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| 4. |
- Ribet, Federico, et al.
(författare)
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Microneedle-based system for minimally invasive continuous monitoring of glucose in the dermal interstitial fluid
- 2018
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Ingår i: 2018 IEEE Micro Electro Mechanical Systems (MEMS). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538647820 ; , s. 408-411
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Konferensbidrag (refereegranskat)abstract
- We present a minimally invasive continuous glucose monitoring (CGM) device. The system consists in an ultra-miniaturized electrochemical sensor probe (70 × 700 × 50 μm3) inserted into the lumen of a hollow silicon microneedle. The implantable portion of the system is 50-fold smaller than state-of-the-art commercial products, thus enabling glucose monitoring in the dermis and a less invasive insertion procedure. Passive interstitial fluid extraction is achieved, making the daily use of this system practically viable. Moreover, the sensor positioning provides minimal delay in tracking glycaemia (5-10 minutes lag), due to the minimal distance between sensing electrodes and microneedle opening. The demonstrated system has therefore the potential to enable minimally invasive, fast and reliable CGM in patients affected by diabetes.
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| 5. |
- Ribet, Federico, et al.
(författare)
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Microneedle Patch for Painless Intradermal Collection of Interstitial Fluid Enabling Multianalyte Measurement of Small Molecules, SARS‐CoV‐2 Antibodies, and Protein Profiling
- 2023
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Ingår i: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659. ; 12:13
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Ribet, Federico, et al.
(författare)
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Minimally invasive and volume-metered extraction of interstitial fluid:bloodless point-of-care sampling for bioanalyte detection
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Sampling of biological fluids is fundamental in health monitoring and, currently, blood analysisis the standard practice. However, blood sampling entails a series of drawbacks including pain,discomfort, and risk of infections. Interstitial fluid, having a good correlation with blood concentrationdynamics for several analytes, is a promising alternative monitoring matrix because it can be sampled ina minimally invasively manner from the skin, without the need for the more invasive and painfulextraction methods used for blood. Currently, there are no simple devices available to sample and storeknown amounts of interstitial fluid. In this work, a painless microneedle-based sampling device designedto extract 1 μL of fluid from the dermis was realized. The sampled liquid is metered and stored in a papermatrix embedded in a microfluidic chip. The sample can then be analyzed using state-of-the-art tools,such as mass spectrometry (LC-MS/MS).
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| 7. |
- Ribet, Federico, et al.
(författare)
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Real-time intradermal continuous glucose monitoring using a minimally invasive microneedle-based system
- 2018
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Ingår i: Biomedical microdevices (Print). - : Springer-Verlag New York. - 1387-2176 .- 1572-8781. ; 20:4
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Tidskriftsartikel (refereegranskat)abstract
- Continuous glucose monitoring (CGM) has the potential to greatly improve diabetes management. The aim of this work is to show a proof-of-concept CGM device which performs minimally invasive and minimally delayed in-situ glucose sensing in the dermal interstitial fluid, combining the advantages of microneedle-based and commercially available CGM systems. The device is based on the integration of an ultra-miniaturized electrochemical sensing probe in the lumen of a single hollow microneedle, separately realized using standard silicon microfabrication methods. By placing the sensing electrodes inside the lumen facing an opening towards the dermal space, real-time measurement purely can be performed relying on molecular diffusion over a short distance. Furthermore, the device relies only on passive capillary lumen filling without the need for complex fluid extraction mechanisms. Importantly, the transdermal portion of the device is 50 times smaller than that of commercial products. This allows access to the dermis and simultaneously reduces tissue trauma, along with being virtually painless during insertion. The three-electrode enzymatic sensor alone was previously proven to have satisfactory sensitivity (1.5 nA/mM), linearity (up to 14 mM), selectivity, and long-term stability (up to 4 days) in-vitro. In this work we combine this sensor technology with microneedles for reliable insertion in forearm skin. In-vivo human tests showed the possibility to correctly and dynamically track glycaemia over time, with approximately 10 min delay with respect to capillary blood control values, in line with the expected physiological lag time. The proposed device can thus reduce discomfort and potentially enable less invasive real-time CGM in diabetic patients.
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| 8. |
- Ribet, Federico, et al.
(författare)
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Ultra-miniaturization of a planar amperometric sensor targeting continuous intradermal glucose monitoring
- 2017
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Ingår i: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 90, s. 577-583
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Tidskriftsartikel (refereegranskat)abstract
- An ultra-miniaturized electrochemical biosensor for continuous glucose monitoring (CGM) is presented. The aim of this work is to demonstrate the possibility of an overall reduction in sensor size to allow minimally invasive glucose monitoring in the interstitial fluid in the dermal region, in contrast to larger state-of-the-art systems, which are necessarily placed in the subcutaneous layer. Moreover, the reduction in size might be a key factor to improve the stability and reliability of transdermal sensors, due to the reduction of the detrimental foreign body reaction and of consequent potential failures. These advantages are combined with lower invasiveness and discomfort for patients. The realized device consists of a microfabricated three-electrode enzymatic sensor with a total surface area of the sensing portion of less than 0.04 mm2, making it the smallest fully integrated planar amperometric glucose sensor area reported to date. The working electrode and counter electrode consist of platinum and are functionalized by drop casting of three polymeric membranes. The on-chip iridium oxide (IrOx) pseudo-reference electrode provides the required stability for measurements under physiological conditions. The device is able to dynamically and linearly measure glucose concentrations in-vitro over the relevant physiological range, while showing sufficient selectivity to known interfering species present in the interstitial fluid, with resolution and sensitivity (1.51 nA/mM) comparable to that of state-of-art commercial CGM systems. This work can therefore enable less invasive and improved CGM in patients affected by diabetes.
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| 9. |
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| 10. |
- Ribet, Federico, et al.
(författare)
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Vertical integration of microchips by magnetic assembly and edge wire bonding
- 2020
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Ingår i: MICROSYSTEMS & NANOENGINEERING. - : NATURE PUBLISHING GROUP. - 2055-7434. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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