bio-MEMS Sensors Research Articles

Design Considerations of Implantable MEMS Sensor for Bladder Pressure Monitoring: A Review

One of the main urinary disorders that impairs the bladder's capacity to regulate urine flow is urinary incontinence (UI). Currently, the new development of wireless implantable MEMS sensors has been studied to replace current clinical test of bladder pressure. This new invention grants a long-term pressure monitoring within the bladder, less painful with non-surgical, reducing the potential of infection thus maintains the patient’s quality of life. However, developing implanted BioMEMS sensors pose challenging tasks due to various constraint requirements that need to be fulfilled such as appropriate measurement ranges and bandwidth, suitable transduction mechanism, biocompatible materials, structural shape and size as well as wireless telemetry capability. This paper presents a review on implantable MEMS sensors and design challenges specifically for bladder pressure monitoring application.

Recent Advances in Magnetic Polymer Composites for BioMEMS: A Review.

The objective of this review is to investigate the potential of functionalized magnetic polymer composites for use in electromagnetic micro-electro-mechanical systems (MEMS) for biomedical applications. The properties that make magnetic polymer composites particularly interesting for application in the biomedical field are their biocompatibility, their adjustable mechanical, chemical, and magnetic properties, as well as their manufacturing versatility, e.g., by 3D printing or by integration in cleanroom microfabrication processes, which makes them accessible for large-scale production to reach the general public. The review first examines recent advancements in magnetic polymer composites that possess unique features such as self-healing capabilities, shape-memory, and biodegradability. This analysis includes an exploration of the materials and fabrication processes involved in the production of these composites, as well as their potential applications. Subsequently, the review focuses on electromagnetic MEMS for biomedical applications (bioMEMS), including microactuators, micropumps, miniaturized drug delivery systems, microvalves, micromixers, and sensors. The analysis encompasses an examination of the materials and manufacturing processes involved and the specific fields of application for each of these biomedical MEMS devices. Finally, the review discusses missed opportunities and possible synergies in the development of next-generation composite materials and bioMEMS sensors and actuators based on magnetic polymer composites.

A Proposal for a Novel Surface-Stress Based BioMEMS Sensor Using an Optical Sensing System for Highly Sensitive Diagnoses of Bio-particles.

In this paper, a BioMEMS sensor by using a surface-stress sensing approach, connected to a highly sensitive optical sensing system, is proposed to diagnose various types of biomolecules. The MEMS transducer is composed of a fixed–fixed beam with immobilized receptors on the surface which is connected to a Ring Resonator (RR) filter. The interaction between the target biomolecules and the receptors induces surface stresses on the beam. This stress results in the beam deformation which leads to changes in the coupling coefficient of the RR. Consequently, the transmission spectrum of the RR experiences changes, measured by using an optical photo-detector. Therefore, by analyzing the response of the photo-detector output, one can detect the number of target biomolecules in the sample and assign a level of contamination, infection or bioparticles, caused by the specific disease. Furthermore, the MEMS functional characteristics and the optical properties of the proposed biosensor are designed and analyzed respectively by using the finite element method (FEM) and the finite difference time domain (FDTD) approach. The obtained functional characteristics of the proposed device show that the present optical BioMEMS sensor can be used for highly sensitive diagnoses of various types of diseases and their progress level.

A Measurement Platform for Label-Free Detection of Biomolecules Based on a Novel Optical BioMEMS Sensor

In this article, a novel optical Bio-microelectromechanical system (MEMS) sensing platform is proposed based on a tunable laser and its lasing wavelength to detect the biomolecules and measure their quantities. The present biosensor consists of a BioMEMS cantilever and a proposed external cavity tunable laser. While the target samples (i.e., DNA, mRNA, or protein) are exposed to the cantilever surface, target-analyte bindings are happened. This can induce a surface stress on the MEMS cantilever and results in its bending due to the surface stress difference in each side of the cantilever. Thus, the gap size between the laser cavity and the gain medium is changed which can be measured by the wavelength variations of the proposed tunable laser source. Consequently, by analyzing the output response, one can detect the amount of target biomolecules in the sample and assign a level of contamination, infection, or bioparticles, caused by the specific disease. Various parameters of the proposed device are designed by numerical and analytical approaches. Furthermore, functional characteristics of the present BioMEMS sensor are obtained as follows: mechanical sensitivity of $1.8~\mu \text{m}$ /Nm−1, optical sensitivity of 422 nm/RIU, Q-factor of 610, and resonant frequency of 6.43 kHz. The obtained functional characteristics of the proposed device show that the present optical BioMEMS sensor can be appealing for highly sensitive diagnoses of various types of diseases and their progress level.

Design of microfluidic experimental setup for the detection of heavy metal ions using piezoresistive BioMEMS sensor

Purpose This paper aims to propose a new microfluidic portable experimental platform for quick detection of heavy metal ions (HMIs) in picomolar range. The experimental setup uses a microfabricated piezoresistive sensor (MPS) array of eight cantilevers with ion-selective self-assembled monolayer's (SAM). Design/methodology/approach Most of the components used in this experimental setup are battery operated and, hence, portable to perform the on-field experiments. HMIs (antigen) and thiol-based SAM (antibody) interaction start bending the microcantilever. This results in a change of resistance, which is directly proportional to the surface stress produced due to the mass of targeted HMIs. The authors have used Cysteamine and 4-Mercaptobenzoic acid as a thiol for creating SAM to test the sensitivity and identify the suitable thiol. Some of the cantilevers are blocked using acetyl chloride to use as a reference for error detection. Findings The portable experimental platform achieves very small detection time of 10-25 min with a lower limit of detection (LOD) 0.762 ng (6.05 pM) for SAM of Cysteamine and 4-Mercaptobenzoic acid to detect Mn2+ ions. This technique has excellent potential and capability to selectively detect Hg2+ ions as low as 2.43 pM/mL using SAM of Homocysteine (Hcys)-Pyridinedicarboxylic acid (PDCA). Research limitations/implications As microcantilever is very thin and fragile, it is challenging to apply a surface coating to have selective detection using Nanadispenser. Some of the cantilevers get broken during this process. Originality/value The excessive use and commercialization of NPs are quickly expanding their toxic impact on health and the environment. Also, LOD is limited to nanomolar range. The proposed method used the combination of thin-film, NPs, and MEMS-based technology to overcome the limitation of NPs-based technique and have picomolar range of HMIs detection.

Design of capacitance based on interdigitated electrode for BioMEMS sensor application

In this paper present, an electrostatic actuation mechanism based on the interdigitated electrode for the Biomedical Micro Electro Mechanical Systems (Bio-MEMS) sensors was mainly used for sensing or actuation in analytical and different detection applications. One of the main things interdigitated electrode (IDE) for capacitance derived from multiple electrode pairs has been connected in parallel with wide proof mass, folded spring beam attached as anchor in the sensor construction. The total capacitance was a sum of capacitance contributed by neighbouring electrodes. Hence the opposite walls of comb electrodes in the overlapping region form a parallel plate capacitor and contribute a capacitance C easily analyzed with fringe capacitance can be estimated to analytically difficult one. However, the nearly accurate way to estimate for the fringe capacitance is by using the finite element method (FEM). The major importance of the geometric dimensions on interdigitated electrode sensors are studied with an analytical model. The design of capacitive based IDE sensors are simulated and demonstrated on visualizing of the electrical properties by COMSOL Multiphysics software.

Utilizing Multiple BioMEMS Sensors to Monitor Orthopaedic Strain and Predict Bone Fracture Healing.

Current diagnostic modalities, such as radiographs or computed tomography, exhibit limited ability to predict the outcome of bone fracture healing. Failed fracture healing after orthopaedic surgical treatments are typically treated by secondary surgery; however, the negative correlation of time between primary and secondary surgeries with resultant health outcome and medical cost accumulation drives the need for improved diagnostic tools. This study describes the simultaneous use of multiple (n = 5) implantable flexible substrate wireless microelectromechanical (fsBioMEMS) sensors adhered to an intramedullary nail (IMN) to quantify the biomechanical environment along the length of fracture fixation hardware during simulated healing in ex vivo ovine tibiae. This study further describes the development of an antenna array for interrogation of five fsBioMEMS sensors simultaneously, and quantifies the ability of these sensors to transmit signal through overlaying soft tissues. The ex vivo data indicated significant differences associated with sensor location on the IMN (p < 0.01) and fracture state (p < 0.01). These data indicate that the fsBioMEMS sensor can serve as a tool to diagnose the current state of fracture healing, and further supports the use of the fsBioMEMS as a means to predict fracture healing due to the known existence of latency between changes in fracture site material properties and radiographic changes. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1873-1880, 2019.

Scalable hybrid microelectronic-microfluidic integration of highly sensitive biosensors

Abstract Point of Care devices for medical applications are becoming more and more widespread. The advantage of having test results after a very short period and without any laboratory creates is beneficial for doctors in developing countries far away from laboratory infrastructure to clinical devices disburdening in-house laboratories for example in case of an outbreak of an epidemic. Especially infectious diseases are one of the world's leading cause of morbidity and death [1]. Viral respiratory infections are a major cause of burden of disease in children. Annual human respiratory syncytial virus (RSV) related death are around 253.000, mainly in developing countries. It accounts for up to 6.7 % of mortality of children younger than 1 year. Therefore, RSV is the second most important global cause of death during infancy. Furthermore, RSV infection has been linked to an increased risk in the development of childhood wheezing and asthma in later life [2, 3]. Fast and cheap diagnostic, independent from laboratory infrastructure, will have a high impact on the healthcare system. Highly sensitive microelectronic biosensors have a superior sensitivity and accuracy compared to paper stripes. The higher miniaturization potential and production stability accompanied by a better readout simplicity makes them a cheaper alternative to optical systems. In this paper a hybrid microelectronic-microfluidic packaging strategy for a disposable for two different microelectronic biosensor platforms will be presented, targeting the diagnostic of RSV. The multiplexed detection of both, host and pathogen biomarkers in the same sample will lead to a rapid, cheap and accurate diagnosis and prognosis, providing almost real-time results. Platform 1, the BioGrFET sensor uses a graphene field effect transistor (GrFET). The liquid sample containing the biomarkers flows over the sensor's surface with probe molecules, where the target molecules (specific biomarkers) of the fluid can be immobilized. The charge of the biomarker on the surface changes the charge carrier density inside the graphene which can be detected by measuring the graphene field effect transport characteristic. Platform 2, the BioMEMS sensor is a micro electro mechanical system (MEMS) having a very thin membrane carrying the active sensor structure, offering additional challenges to device packaging. The liquid sample, containing the biomarkers, flows over the membrane's surface with detection molecules, where the specific biomarkers of the fluid can be immobilized. With the specific biomarkers on the membrane's surface changes the mass and therefore the resonance frequency of the membrane which can be read out. Specific packaging challenge for both sensors is to develop packaging technology flows that allow to add the sensor functionalization during packaging and leaves this functionalization intact until the packaging processes are finalized, which implies a process selection with reduced thermal and mechanical load on the delicate functionalized sensors. This challenge has been mastered for both sensors – yielding two dedicated packaging process flows that were used to manufacture functional sensor packages.

Self powered biomems sensor for hydrocephalus shunts

Self powered biomems sensor for hydrocephalus shunts

Wireless Powering System for Implantable Bio-Mems Sensor

The aim of this proposal is to design a wireless powering system for an Implantable Bio-MEMS Sensor which is used to power up the implanted sensor inside the human body. It is highly desirable due to obviation of batteries or piercing wirings. The implanted sensor is powered up it senses the measureable parameters in the human body and the sensed signals are transmitted to the receiver section that is kept outside the human body. RF powering relies on an inductively coupled electromagnetic link to wirelessly transmit RF power from an external unit to an implanted system. This technique has been widely used for biomedical implants. The system consideration including the inductive coupling and the circuit building blocks of power management are given.

A Wireless Bio-MEMS Sensor for C-Reactive Protein Detection Based on Nanomechanics

A quick wireless label-free detection of disease-related C-reactive proteins (CRPs) using a 200-microm-long microelectromechanical systems (MEMS) microcantilever housed in a 7 x 7 mm(2) reaction chamber with a safe reusable feature is reported. The assay time ranges from about 30 min to 3 h, depending on accuracy. The deflection of the microcantilever due to specific CRP-antiCRP binding is detected using a position-sensitive detector. The converted bio-signal is transmitted by a custom designed wireless amplitude-shift-keying (ASK) transceiver IC fabricated in a 0.18 microm CMOS process. CRP concentrations from 1 microg/mL to 500 microg/mL can be detected. A 0.2-Hz 1-V ac signal instead of traditional bases/acids is applied to the bio-MEMS sensor to unbind the CRP from the microcantilever for reusability.

Membrane thickness design of implantable bio-MEMS sensors for the in-situ monitoring of blood flow

This paper presents some ideas for the membrane thickness design of of implantable bio-micro-electro-mechanical systems (bio-MEMS) for the in situ monitoring of blood flow. The objective is to develop a smart wireless sensing unit for non-invasive early stenosis detection in heart bypass grafts. The design includes considerations of nonlinear material models, multiscale blood flows, and appropriate analyical models for data interpretation, as well as preliminary studies of the pressure and flow sensing concepts. The paper also examines the use of surface coatings for the design on biocompatibility and non-adhesion of blood platelets and constituents. The implications of the results are discussed for in vivo deployment of such sensor systems.

In Vivo Batteryless Wireless Communication System for Bio-MEMS Sensors

We propose a batteryless wireless communication system for in vivo healthcare chips. The system uses inductive coupling at 13.56 MHz with internal and external coils, and employs pulse interval modulation (PIM) to endure the large attenuation in the human body. A wireless communication circuit is presented in this paper, and 16 mV of output voltage can be obtained at the external receiver. The antenna coil structure is investigated, and it is found that a tablet structure is suitable for the proposed system.

Ultrasensitive Biomems Sensors Based on Microcantilevers Patterned with Environmentally Responsive Hydrogels

An innovative platform was developed for ultrasensitive microsensors based on microcantilevers patterned with crosslinked copolymeric hydrogels. A novel UV free-radical photolithography process was utilized to precisely align and pattern environmentally responsive hydrogels onto silicon microcantilevers, after microcantilevers were fabricated and released. Specifically, a crosslinked poly(methacrylic acid) network containing high amounts of poly(ethylene glycol) dimethacrylate was prepared and investigated. Hydrogels were patterned onto the silicon microcantilevers utilizing a mask aligner to allow for precise positioning. The silicon surface was modified with γ-methacryloxypropyl trimethoxysilane to gain covalent adhesion between the polymer and the silicon. The hydrogels sensed and responded to changes in environmental pH resulting in a variation in surface stress that deflected the microcantilever. The bending response of patterned cantilevers with a change in environmental pH was observed, showing the possibility to construct MEMS/BioMEMS sensors based on microcantilevers patterned with environmentally responsive hydrogels. An extraordinary maximum sensitivity of 1 nm/5×10−5ΔpH was observed, demonstrating the ultrasensitivity of this microsensor platform.