BioMEMS Devices Research Articles

Recognition and capture of breast cancer cells using an antibody-based platform in a microelectromechanical systems device

Cancer is one of the most common diseases afflicting humans. The use of biomarkers specific for tumor cells has facilitated their identification. However, technology has not kept pace with the field of molecular biomarkers, leaving their potential unrealized. Here, we demonstrate the efficacy of recognizing and capturing cancer cells using an antibody-based, on-chip, microfluidic device. A cancer cell capture biochip consisting of microchannels of size 2.0 cm long and 500 microm wide and deep, was etched onto Polydimethylsiloxane. Epithelial membrane antigen (EMA) and Epithelial growth factor receptor (EGFR) were coated on the inner surface of the microchannels. The overall chip measured 2.0 cm x 1.5 cm x 0.5 cm. Normal and tumor breast cells in a phosphate buffered saline (PBS) suspension were flowed through the biochip channels at a rate of 15 microL/min. Breast cancer cells were preferentially captured and identified while most of normal cells passed through. The capture rates for tumor and normal cells were found to be >30% and <5%, respectively. This preliminary cancer cell capture biochip design supports our initial effort of moving a BioMEMS device, from the bench top to the clinic.

Control of Bio-MEMS Surface Chemical Properties in Micro Fluidic Devices for Biological Applications

Surface chemistry of silicon/glass based bio-MEMS was controlled by depositing plasma polymerized acrylic acid (ppAc) films at two different electrode positions in a two-stage plasma reactor. AFM and XPS were used to characterize the surface roughness and surface chemistry of the films, respectively. The surface of bio-MEMS was highly functionalized with carboxylic/ester functionalities with a very good surface uniformity. The proportion of carbon atoms as C-OX, C(==O)OX functionalities was decreased and an increase in C==O functionalities was observed when the electrode position was increased from the mesh. These functionalized bio-MEMS devices have advantages in fabrication of reusable micro fluidic devices and the variation of fluid velocity by changing the surface properties may be used to develop a micro-mixing system to control the mixing ratio of different fluids for different biological and chemical applications.

Glass-based BioMEMS devices for optically excited cell impedance measurement

This paper presents for the first time the design and fabrication of BioMEMS devices for living cells’ electrochemical impedance measurement under optical excitation. An interdigitated electrode design is adopted in order to increase the sensitivity of living cells’ impedance measurement. The magnitudes of the parasitic components were calculated and their influence on the chip performance was simulated. It is shown that our glass-based realization enables a very good performance up to a measurement frequency of 10 MHz when the solution resistance is 1 MΩ. The main difficulties that had to be solved in the fabrication process were related to adhesion and patterning of the various metal films, and especially to developing the correct bonding recipe. Unlike most of the reported data, no direct bonding was employed in the realization of our devices, but rather an intermediary polymer layer (e.g. SU8 or BCB) was used. The impedance of the devices with living yeast cells are measured with and without laser excitation at 532 nm. The laser excitation also redistributes the cells, and the suspending cells in the PBS buffer settle down much quicker after the light excitation.

A hybrid approach for fabrication of polymeric BIOMEMS devices

Polymeric microfluidic chips are an enabling component for cost-effective, point of care analytical devices for pharmaceutical, agriculture, health, biological and medical applications. The microfluidic structures can be completed with active elements like pumps and valves as well as sensor components for more complex so called total analysis systems. Often, systems are designed as reader and disposable cartridge where the fluidic structures are simple devices that will be inserted into the reader, which executes the analytical protocol and displays the information in digital form, and disposed after completion of the analysis. In this paper, a hybrid fabrication approach was employed to build a polymeric microfluidic device, so-called sweatstick, suitable for collecting small, precise amounts (600 μl) of human sweat, which were further analyzed for the amount of calcium ions indicating bone mass loss. The device was assembled from different parts fabricated by ultra deep X-ray lithography, precision micro-milling, and molding. Surface treatment of liquid exposed surfaces by oxygen plasma ensures hydrophilic behavior and proper capillary action. Preliminary testing of the device was performed by collecting defined amounts of sweat simulant and determining the calcium ion content using a fluorescent technique. The results for low calcium ion concentration typical for human sweat were excellent and repeatable with variation less than 5% demonstrating the ability to perform indirect bone loss measurements.

Biofunctionalization of PMMA-based BioMEMS Devices for Breast Cancer Diagnosis

not Available.

Urine-activated paper batteries for biosystems**A portion of this paper was presented at The 4th International Workshop on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2004), 28–30 November, 2004, Kyoto, Japan.

The first urine-activated laminated paper batteries have been demonstrated and reported in this paper. A simple and cheap fabrication process for the paper batteries has been developed which is compatible with the existing plastic laminating technologies or plastic molding technologies. In this battery, a magnesium (Mg) layer and copper chloride (CuCl) in the filter paper are used as the anode and the cathode, respectively. A stack consisting of a Mg layer, CuCl-doped filter paper and a copper (Cu) layer sandwiched between two plastic layers is laminated into the paper batteries by passing through the heating roller at 120 °C. The paper battery is tested and it can deliver a power greater than 1.5 mW. In addition, these urine-activated laminated paper batteries could be integrated with bioMEMS devices such as home-based health test kits providing a power source for the electronic circuit.

Determination of Elastic Modulus of Piezoelectric Aluminum Nitride Coating

AbstractAluminum Nitride (AlN) is a technologically important wide band gap semiconductor and a potential piezo-electric material for Biosensor application [1]. It is a clear candidate for the integration of surface acoustic wave (SAW) devices on chips with silicon-based electronics [2]. AlN may also prove to be useful for the integration of mechanical devices and also in the field of packaging of Bio-MEMS devices because of its superior thermal conductivity 130-140 (W/mK, room temp-100 deg C) and nontoxicity. In the current work an attempt has been made to determine the elastic modulus of AlN coated on Si-microcantilevers, employing the concept of symmetrically laminated beam theory for the first time at the micro level thus avoiding the coupling effects. So far the earlier studies have been done only using simple beam theory. Modal vibration frequencies for microcantilevers without and with the AlN coating were used, along with analytical models and knowledge of the Si modulus, to “back out” the modulus of AlN [3].

2P1-N-092 培養心筋細胞を駆動源とするバイオマイクロアクチュエータを用いたBioMEMSデバイスの創成 : 心筋細胞シートを用いた超微量マイクロポンプの実現(MEMSとナノテクノロジー2,生活を支援するロボメカ技術のメガインテグレーション)

2P1-N-092 培養心筋細胞を駆動源とするバイオマイクロアクチュエータを用いたBioMEMSデバイスの創成 : 心筋細胞シートを用いた超微量マイクロポンプの実現(MEMSとナノテクノロジー2,生活を支援するロボメカ技術のメガインテグレーション)

Self-assembly of micro parts on normal glass substrate *

Abstract Fluidic self-assembly is an approach by which micro parts less than one millimeter in size can be driven by the capillary force of a certain adhesive liquid and be fixed onto the desired sites on some substrates. Normal glass with the composition of Na2SiO3CaSiO34SiO2 has been widely used in fluidic microelectromechanical systems (MEMS) and bio-MEMS devices. We investigate the MEMS self-assembly experiment on normal glass substrate. The results of scanning electron microscopy (SEM) show that micro-parts of 400 μm × 400 μm squares can be precisely assembled in the expected area of the normal glass substrate.

Surface modification of silicon and gold-patterned silicon surfaces for improved biocompatibility and cell patterning selectivity

Clean silicon and gold-patterned silicon platforms were modified with methoxy-polyethylene glycol (M-PEG silane) via a self-assembly technique, which significantly improved their plasma protein resistance capability and cell patterning selectivity. Fibrinogen and IgG were used as model plasma proteins to study the efficacy of PEG layers in resisting protein adsorption. Selective cell patterning on the gold regions of a gold-patterned silicon substrate and tissue compatibility were studied with macrophage and fibroblast cells. The research also revealed how the presence of gold electrodes on a silicon substrate would influence the cell patterning selectivity. Our experimental results showed that the PEG-modified silicon surfaces had a high resistivity to protein and cell attachment and that the PEG-modified gold-patterned silicon surfaces nearly completely eliminated the protein adsorption and cell attachment on silicon. This study provides a new approach to developing biocompatible surfaces for silicon-based BioMEMS devices, particularly for biosensors where a metal-insulator format must be enforced.

High Performance P(VDF-TrFE-CFE) Terpolymer for BioMEMs and Microfluidic Devices

ABSTRACTBioMEMs and microfluidic devices have gained a lot of attention in recent years due to their emerging applications in biochemical analysis, medical diagnosis, chemical analysis and synthesis, drug discovery and drug delivery, biosensing and biomimetic systems. The materials requirements for bioMEMs are biocompatible, chemically modifiable, easy to fabricate, economic, compliable and smart. Among various materials, the electroactive polymeric materials can best meet these requirements. Recently, we developed a group of poly(vinylidene fluoride-trifluoroethylene) P(VDF-TrFE) based terpolymers which have very high strain level and high energy density. The longitudinal and transverse strain of these materials can reach about –7% and 4.5%, and the elastic energy density is around 1.1 J/cm3, which are very attractive for the development of polymeric pump, valve and other microfluidic components for all polymer-based bioMEMs and microfluidic integrated system. This paper reports on the recent efforts on the optimization of the terpolymer performance and development of microfluidic components using the electroactive terpolymers for bioMEMs.

Ultraviolet-curable polymerswith chemically bonded carbon nanotubes formicroelectromechanical system applications

Current UV-curable polymer techniques formicroelectromechanical system fabrication pose certainchallenges due to the electrical and mechanical properties of thepolymer. A novel UV-curable polymer uniformly bonded withfunctionalized nanotubes was synthesized via a modifiedthree-step in situ polymerization. Purified multi-wallednanotubes, obtained by the microwave chemical vapor depositionmethod, were functionalized by oxidation. X-ray photoelectronspectroscopy was used to identify the -OH and -COOH groupsattached to the nanotube surface. The UV-curable polymer was preparedfrom toluene diisocyanate (TDI), functionalized nanotubes, and2-hydroxyethyl methacrylate (HEMA). The chemical bonds between the-NCO groups of TDI and the -OH, -COOH groups of functionalizednanotubes were confirmed by Fourier transform infrared spectra.This new UV-curable polymer is expected to be a cost-effectivesolution with a variety of applications in UV coating, phaseshifters for telecommunications and global positioning systems,and polymer and BioMEMS devices.

BioMEMS device with integrated microdialysis probe and biosensor array

The fabrication of a microdevice for continuous sampling and on-line monitoring of glucose is described. The device comprised a microdialysis sampling system integrated on the flow through channel of a microfabricated enzyme sensor. The sensor was produced by thin film technology and was assembled to a printed circuit board (PCB) that provided the means for both electrical and fluidic connections. A polyacrilonitrile fibre, with a cut-off of 50 kDa, was used in the fabrication of the sampling probe. The performance of the device was evaluated in-vitro. High sampling efficiency of the microdialysis probe was achieved by appropriate selection of the perfusion fluid flow rate. Response times varying from 1.5 to 3.0 min were determined for flow rates ranging between 1 and 0.2 μl/min. The linear response range was up to 30 mM glucose and interference from other electroactive substances was almost negligible. The device showed excellent stability under continuous operation for at least 5 days and sensitivity variation less than 3% over a period of 15 days.

Aerosol-Based Direct-Write of Biological Materials for Biomedical Applications

ABSTRACTApplying life sciences and engineering principles to the study of cells and engineered tissue has resulted in various successes. These endeavors are poised towards development of functional neo-organs used as native tissue substitutes. Concurrent with this goal, research arenas are directed in the general areas of biocompatible polymer scaffolds, biomimmetic extracellular matrices, control of stem cell differentiation, biomolecule signaling, and directed material delivery. Optomec Inc. is developing an aerosol-based direct-write process for deposition of biological materials into three dimensional, micron-scale patterns. The process uses pneumatic atomization to produce aerosol droplets of proteinacious colloidal dispersions and whole cell suspensions. The droplets are entrained in an air stream and deposited with a proprietary deposition tool. The biological materials can be seeded into three dimensional polymer scaffolds and various substrate surfaces. Optomec's direct write process has applicability to the additive fabrication of engineered tissue. Other applications of the direct write tool include rapid prototyping of analytical biosensors, hybrid BioMEMS, and bio-chip microarray devices.