Biomedical Microdevices

Publications in this journal

• Article: Selective bacterial patterning using the submerged properties of microbeads on agarose gel.

  Sung Jun Park, Hyeoni Bae, Seong Young Ko, Jung-Joon Min, Jong-Oh Park, Sukho Park
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  ABSTRACT: We proposed a new bacteria patterning method on the restricted region of microbeads, using the submerged property of polystyrene microbeads on various concentrations of agarose gel. Moreover, we fabricated a bacterial microrobot using attenuated Salmonella typhimurium through the new patterning methods. We controlled the submerged degree of polystyrene microbeads through the regulation of the hardness of the agarose gel. The polystyrene microbeads on agarose gel were transferred onto a poly-dimethylsiloxane (PDMS) surface for easy manipulation of the microbeads. Then, we treated the polystyrene microbeads on the PDMS surface with antibacterial adherent factors, such as O2 plasma and bovine serum albumin (BSA). The Salmonella typhimurium was attached to the entire surface of the untreated polystyrene microbeads, whereas Salmonella typhimurium were only attached to the restricted surface region of the treated polystyrene microbeads through the proposed patterning method. The bacteria-attached microbeads gain motility by the propulsion of the attached bacteria, and the selective-bacteria-attached microbeads showed enhanced motility. Compared with whole-bacteria-attached polystyrene microbeads (1.74 ± 1.62 μm/s), the selective bacteria-attached polystyrene microbeads, using O2 plasma and BSA, showed 9.18 ± 1.88 μm/s and 14.65 ± 8.66 μm/s faster moving velocities, respectively. Through the results, we expected that the proposed patterning methodology of microbeads could contribute to the development of biomedical bacterial microrobots.
  Biomedical Microdevices 05/2013;
• Article: Tower microneedle minimizes vitreal reflux in intravitreal injection.

  Chang Yeol Lee, Yong Sung You, Sung Ho Lee, Hyungil Jung
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  ABSTRACT: Intravitreal injection is widely used for easy control of drug levels in posterior segment of the eye by injecting the drug directly with hypodermic needles. Patients, however, often experience complications from intravitreal injection due to repeated injections, increased intraocular pressure, and infection. In addition, injected drug reflux after intravitreal injection makes it challenging to maintain predetermined drug dose due to the drug loss through backward effusions. Here, we described that the Tower Microneedle can reduce initial reflux and bleb formation due to its smaller outer diameter compared to a traditional hypodermic needle. Furthermore, we use phenylephrine hydrochloride for pupil expansion and demonstrated that Tower Microneedle induced similar pupil expansions using only half the drug volume, in the same period of time, compared to the 31 Gauge hypodermic needle. Consequently, Tower Microneedle achieves the same therapeutic effect in the vitreous body using fewer drugs than a traditional hypodermic needle due to the decreased backward drug effusion. Tower Microneedle described herein holds great promise for intravitreal injection with less reflux and lower drug dosage.
  Biomedical Microdevices 05/2013;
• Article: Design and test of a MEMS strain-sensing device for monitoring artificial knee implants.

  W Hasenkamp, N Thevenaz, J Villard, A Bertsch, A Arami, K Aminian, A Terrier, P Renaud
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  ABSTRACT: This paper describes the development of a polyimide-based MEMS strain-sensing device. Finite element analysis was used to investigate an artificial knee implant and assist on device design and to optimize sensing characteristics. The sensing element of the device was fabricated using polyimide micromachining with embedded thin-metallic wires and placed into a knee prosthesis. The device was evaluated experimentally in a mechanical knee simulator using static and dynamic axial load conditions similar to those encountered in vivo. Results indicates the sensor is capable of measuring the strain associated to the total axial forces in the range of approximately 4 times body weight with a good sensitivity and accuracy for events happening within 1 s time window.
  Biomedical Microdevices 05/2013;
• Article: Polymeric microfluidic devices exhibiting sufficient capture of cancer cell line for isolation of circulating tumor cells.

  Takashi Ohnaga, Yutaka Shimada, Makoto Moriyama, Hiroyuki Kishi, Tsutomu Obata, Koji Takata, Tomoyuki Okumura, Takuya Nagata, Atsushi Muraguchi, Kazuhiro Tsukada
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  ABSTRACT: Here, we developed polymeric microfluidic devices for the isolation of circulating tumor cells. The devices, with more than 30,000 microposts in the channel, were produced successfully by a UV light-curing process lasting 3 min. The device surface was coated with anti-epithelial cell adhesion molecule antibody by just contacting the antibody solution, and a flow system including the device was established to send a cell suspension through it. We carried out flow tests for evaluation of the device's ability to capture tumor cells using an esophageal cancer cell line, KYSE220, dispersed in phosphate-buffered saline or mononuclear cell separation from whole blood. After the suspension flowed through the chip, many cells were seen to be captured on the microposts coated with the antibody, whereas there were few cells in the device without the antibody. Owing to the transparency of the device, we could observe the intact and the stained cells captured on the microposts by transmitted light microscopy and phase contrast microscopy, in addition to fluorescent microscopy, which required fluorescence labeling. Cell capture efficiencies (i.e., recovery rates of the flowing cancer cells by capture with the microfluidic device) were measured. The resulting values were 0.88 and 0.95 for cell suspension in phosphate-buffered saline, and 0.85 for the suspension in the mononuclear cell separation, suggesting the sufficiency of this device for the isolation of circulating tumor cells. Therefore, our device may be useful for research and treatments that rely on investigation of circulating tumor cells in the blood of cancer patients.
  Biomedical Microdevices 05/2013;
• Article: Flexible probe for in vivo quantification of corneal epithelium permeability through non-invasive tetrapolar impedance measurements.

  A Guimerà, X Illa, E Traver, M Plata-Cordero, J Yeste, C Herrero, C Lagunas, M J Maldonado, R Villa
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  ABSTRACT: Studies concerning the functional status of the corneal epithelium are of special interest due to its key role in preventing ocular surface disease and corneal infections. In particular, quantitative measurements of the epithelium permeability translayer electrical resistance (TER) have been proven as a sensitive in vitro test for evaluation of the corneal barrier function. In a recent work from the authors (Guimera et al. Biosens. Bioelectron. 31:55-61, 2012), a novel method to non-invasively assess the corneal epithelial permeability by using tetrapolar impedance measurements, based on the same TER theoretical principles, was presented and validated using a rigid sensing device. In this work, the usability of this method has been dramatically improved by using SU-8 photoresist as a substrate material. The flexibility of this novel sensing device makes no need to apply pressure on the cornea to ensure the electrical contact between the electrodes and the corneal surface. The feasibility of this flexible sensor has been evaluated in vivo by increasing the permeability of rabbit corneal epithelium. For that, different concentrations of benzalkonium chloride (BAC) solution were instilled on different rabbit corneas. The obtained results have been compared with measurements of the permeability to sodium fluorescein of different excised corneas, a well-known method used to evaluate the corneal barrier function, to demonstrate the feasibility of this novel flexible sensor for quantifying the corneal epithelium permeability in vivo in a non-invasive way.
  Biomedical Microdevices 05/2013;
• Article: Subcutaneous blood pressure monitoring with an implantable optical sensor.

  Michael Theodor, Dominic Ruh, Jens Fiala, Katharina Förster, Claudia Heilmann, Yiannos Manoli, Friedhelm Beyersdorf, Hans Zappe, Andreas Seifert
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  ABSTRACT: We introduce a minimally invasive, implantable system that uses pulse transit time to determine blood pressure. In contrast to previous approaches, the pulse wave is detected by a photoplethysmographic (PPG) signal, acquired with high quality directly on subcutaneous muscle tissue. Electrocardiograms (ECG) were measured with flexible, implantable electrodes on the same tissue. PPG detection is realized by a flat 20 mm x 6 mm optoelectronic pulse oximeter working in reflection mode. The optical sensor as well as the ECG electrodes can be implanted using minimally invasive techniques, with only a small incision into the skin, making long-term monitoring of blood pressure in day-to-day life for high-risk patients possible. The in vivo measurements presented here show that the deviation to intra-arterial reference measurements of the systolic blood pressure in a physiologically relevant range is only 5.5 mmHg, demonstrated for more than 12 000 pulses. This makes the presented sensor a grade B blood pressure monitor.
  Biomedical Microdevices 05/2013;
• Article: On-chip parallel detection of foodborne pathogens using loop-mediated isothermal amplification.

  Carlos Duarte, Eric Salm, Brian Dorvel, Bobby Reddy, Rashid Bashir
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  ABSTRACT: According to estimates issued by the Center for Disease Control and Prevention, one out of six Americans will get sick during this year due to consumption of contaminated products and there will be 50,000 related hospitalizations. To control and treat the responsible foodborne diseases, rapid and accurate detection of pathogens is extremely important. A portable device capable of performing nucleic acid amplification will enable the effective detection of infectious agents in multiple settings, leading to better enforcement of food safety regulations. This work demonstrates the multiplexed detection of food pathogens through loop-mediated isothermal amplification on a silicon chip. Silane passivation is used to prevent the adsorption of the polymerase on silicon oxide, which can severely inhibit nucleic acid amplification. We demonstrate the multiplexed screening of virulence genes of Listeria monocytogenes, Escherichia coli, and Salmonella by dehydrating the corresponding primers in oxidized silicon wells. Droplets of 30 nL with reagents for nucleic acid amplification and lysate of suspected pathogens are arrayed on micro-machined wells with an automated microinjection system. We show that dehydrated primers re-suspend when other reagents are microinjected, and the resulting mix can be used to specifically amplify the targeted gene. Results of characterization experiments demonstrate sensitivity down to a few templates per reaction, specificity that enables multiplexed screening, and robustness that allows amplification without DNA extraction.
  Biomedical Microdevices 04/2013;
• Article: In vitro and In vivo anticancer activity of surface modified paclitaxel attached hydroxyapatite and titanium dioxide nanoparticles.

  G Devanand Venkatasubbu, S Ramasamy, G Pramod Reddy, J Kumar
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  ABSTRACT: Targeted drug delivery using nanocrystalline materials delivers the drug at the deseased site. This increases the efficacy of the drug in killing the cancer cells. Surface modifications were done to target the drug to a particular receptor on the cell surface. This paper reports synthesis of hydroxyapatite and titanium dioxide nanoparticles and modification of their surface with polyethylene glycol (PEG) followed by folic acid (FA). Paclitaxel, an anticancer drug, is attached to functionalized hydroxyapatite and titanium dioxide nanoparticles. The pure and functionalised nanoparticles are characterised with XRD, TEM and UV spectroscopy. Anticancer analysis was carried out in DEN induced hepatocarcinoma animals. Biochemical, hematological and histopathological analysis show that the surface modified paclitaxel attached nanoparticles have an higher anticancer activity than the pure paclitaxel and surface modified nanoparticles without paclitaxel. This is due to the targeting of the drug to the folate receptor in the cancer cells.
  Biomedical Microdevices 04/2013;
• Article: Biomolecule screening for efficient attachment of biofunctionalized microparticles to the zona pellucida of mammalian oocytes and embryos.

  Sergio Novo, Elena Ibáñez, Leonardo Barrios, Onofre Castell, Carme Nogués
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  ABSTRACT: Individual tagging of oocytes and embryos through the attachment of micrometer-sized polysilicon barcodes to their zona pellucida (ZP) is a promising approach to ensure their correct identification and traceability in human assisted reproduction and in animal production programs. To provide barcodes with the capacity of binding to the ZP, they must be first biofunctionalized with a biomolecule capable of binding to the ZP of both oocytes and embryos. The aim of this work was to select, among an anti-ZP2 antibody and the two lectins wheat germ agglutinin (WGA) and phytohemagglutinin-L, the most optimal biomolecule for the eventual biofunctionalization of barcodes, using mouse oocytes and embryos and commercially available microspheres as a model. Despite the anti-ZP2 antibody showed the highest number of binding sites onto the ZP surface, as determined by field emission scanning electron microscopy, the binding of anti-ZP2-biofunctionalized microspheres to the ZP of cultured oocytes and embryos was less robust and less stable than the binding of lectin-biofunctionalized ones. WGA proved to be, among the three candidates tested, the most appropriate biomolecule to biofunctionalize microparticles with the aim to attach them to the ZP of both oocytes and embryos and to maintain them attached through oocyte activation (zona reaction) and in vitro culture up to the blastocyst stage. As saccharides recognized by WGA are highly abundant in the ZP of most mammalian species, WGA-biofuncionalized microparticles would be able to attach to the ZP of oocytes/embryos of species other than the mouse, such as humans and farm animals.
  Biomedical Microdevices 04/2013;
• Article: The cell engineering construction and function evaluation of multi-layer biochip dialyzer.

  Wen Zhu, Jiwei Li, Jianfeng Liu
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  ABSTRACT: We report the fabrication and function evaluation of multi-layer biochip dialyzer. Such device may potentially be applied to the wearable hemodialysis systems. By merging the advantages of microfluidic chip technology with cell engineering, both functions of glomerular filtration and renal tubule physiological activity are integrated in the same device. This device is designed into a laminated structure, in which the chip number of the superimposed layer can be arbitrarily tailored in accordance with the requirements of dialysis capacity. We propose that such structure can overcome the obstacles of large size and detached structure of the traditional hollow fiber dialyzer. To construct this multilayer biochips dialyzer, two types of dialyzer device with two-layered and six-layered chips are assembled, respectively. Cell adhesion and proliferation on three different dialysis membrane materials under static and dynamic conditions are investigated and compared. The filtration capability, re-absorption function and excrete ammonia function of the resulting multi-layer biochip dialyzer are evaluated. The results reveal that the constructed device can perform higher filtration efficiency and also play a role of renal tubule. This methodology may be useful in developing "scaling down" artificial kidneys that can act as wearable or even implantable hemodialysis systems.
  Biomedical Microdevices 04/2013;
• Article: A microfluidic device mimicking acinar concentration gradients across the liver acinus.

  Ming-Cheng Shih, Shih-Heng Tseng, Yu-Shih Weng, I-Ming Chu, Cheng-Hsien Liu
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  ABSTRACT: The acinus-mimicking microfluidic chip, which simulates the in vivo condition of the liver, was developed and reported in this paper. The gradient microenvironment of the liver acinus is replicated within this proposed microfluidic chip. The advantage of this acinus-mimicking chip is capable of adjusting the concentration gradient in a relatively short period of time at around 10 s. At the same instance the non-linear concentration gradient can be presented in the various zones within this microfluidic chip. The other advantage of this proposed design is in the convenience of allowing the direct injection of the cells into the chip. The environment within the chip is multi-welled and gel-free with high cell density. The multi-row pillar microstructure located at the entrance of the top and bottom flow channels is designed to be able to balance the pressure of the perfusion medium. Through this mechanism the shear stress experienced by the cultured cells can be minimized to reduce the potential damage flow from the perfusion process. ((3))The fluorescence staining and the observations of the cell morphology verify the life and death of the cells. The shear stress experienced by the cells in the various zones within the chip can be effectively mapped. The serum glutamic oxaloacetic transaminase (SGOT) collected from the supernatants was used to determine the effects of the degassing process and the shear stress of the medium flow on the cultured cells.
  Biomedical Microdevices 04/2013;
• Article: Microengineered tumor models: insights & opportunities from a physical sciences-oncology perspective.

  Peter Delnero, Young Hye Song, Claudia Fischbach
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  ABSTRACT: Prevailing evidence has established the fundamental role of microenvironmental conditions in tumorigenesis. However, the ability to identify, interrupt, and translate the underlying cellular and molecular mechanisms into meaningful therapies remains limited, due in part to a lack of organotypic culture systems that accurately recapitulate tumor physiology. Integration of tissue engineering with microfabrication technologies has the potential to address this challenge and mimic tumor heterogeneity with pathological fidelity. Specifically, this approach allows recapitulating global changes of tissue-level phenomena, while also controlling microscale variability of various conditions including spatiotemporal presentation of soluble signals, biochemical and physical characteristics of the extracellular matrix, and cellular composition. Such platforms have continued to elucidate the role of the microenvironment in cancer pathogenesis and significantly improve drug discovery and screening, particularly for therapies that target tumor-enabling stromal components. This review discusses some of the landmark efforts in the field of micro-tumor engineering with a particular emphasis on deregulated tissue organization and mass transport phenomena in the tumor microenvironment.
  Biomedical Microdevices 04/2013;
• Article: Continuous in vivo blood pressure measurements using a fully implantable wireless SAW sensor.

  Olive H Murphy, Mohammad Reza Bahmanyar, Alessandro Borghi, Christopher N McLeod, Manoraj Navaratnarajah, Magdi H Yacoub, Christofer Toumazou
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  ABSTRACT: In this paper, the development of a fully implantable wireless sensor able to provide continuous real-time accurate pressure measurements is presented. Surface Acoustic Wave (SAW) technology was used to deposit resonators on crystalline quartz wafers; the wafers were then assembled to produce a pressure sensitive device. Excitation and reading via a miniature antenna attached to the pressure sensor enables continuous external interrogation. The main advantages of such a configuration are the long term stability of quartz and the low power necessary for the interrogation, which allows 24/7 interrogation by means of a hand-held, battery powered device. Such data are of vital importance to clinicians monitoring and treating the effects of hypertension and heart failure. A prototype was designed and tested using both a bio-phantom test rig and an animal model. The pressure traces for both compare very well with a commercially available catheter tip pressure transducer. The work presented in this paper is the first known wireless pressure data from the left ventricle of the heart of a living swine.
  Biomedical Microdevices 04/2013;
• Article: Development of fluorescent nanoparticle-labeled lateral flow assay for the detection of nucleic acids.

  Yuhong Wang, Sam R Nugen
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  ABSTRACT: The rapid, specific and sensitive detection of nucleic acids is of utmost importance for the identification of infectious agents, diagnosis and treatment of genetic diseases, and the detection of pathogens related to human health and safety. Here we report the development of a simple and sensitive nucleic acid sequence-based and Ru(bpy)3 (2+)-doped silica nanoparticle-labeled lateral flow assay which achieves low limit of detection by using fluorescencent nanoparticles. The detection of the synthetic nucleic acid sequences representative of Trypanosoma mRNA, the causative agent for African sleeping sickness, was utilized to demonstrate this assay. The 30 nm spherical Ru(bpy)3 (2+)-doped silica nanoparticles were prepared in aqueous medium by a novel method recently reported. The nanoparticles were modified by 3-glycidoxypropyl trimethoxysilane in order to conjugate to amine-capped oligonucleotide reporter probes. The fluorescent intensities of the fluorescent assays were quantified on a mictrotiter plate reader using a custom holder. The experimental results showed that the lateral flow fluorescent assay developed was more sensitive compared with the traditional colloidal gold test strips. The limit of detection for the fluorescent lateral flow assay developed is approximately 0.066 fmols as compared to approximately 15 fmols for the colloidal gold. The limit of detection can further be reduced about one order of magnitude when "dipstick" format was used.
  Biomedical Microdevices 03/2013;
• Article: Enrichment of tumor-initiating breast cancer cells within a mammosphere-culture microdevice.

  Katayoon Saadin, Jeffrey M Burke, Neerav P Patel, Rebecca E Zubajlo, Ian M White
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  ABSTRACT: We report for the first time a microdevice that enables the selective enrichment, culture, and identification of tumor-initiating cells on native polydimethylsiloxane (PDMS). For nearly a decade, researchers have identified tumor-initiating breast cancer cells within heterogeneous populations of breast cancer cells by utilizing low-attachment serum-free culture conditions, which lead to the formation of spheroidal colonies (mammospheres) that are enriched for tumor-initiating cells. However, the utility of this assay has been limited by difficulties in combining this culture-plate-based technique with other cellular and molecular analyses. Integrating the mammosphere technique into a microsystem can enable it to be combined directly with a number of functions, such as cell sorting, drug screens, and molecular assays. In this work, we demonstrate mammosphere culture within a PDMS microdevice. We first prove that a native hydrophobic PDMS surface is as effective as commercial low-attachment plates at selectively promoting the formation of mammospheres. We then experimentally assess the PDMS microdevice. Time-lapse images of mammosphere formation within the microdevice show that mammospheres form from single cells or small clusters of cells. Following formation of the mammospheres, it is desirable to evaluate the cells within the spheroids for enrichment of tumor initiating cells. To perform assays such as this (which require the loading and rinsing of reagents) without flushing the cells (which are in suspension) from the device, the culture chamber is separated from a reagent reservoir by a commercially available microporous membrane, and thus reagents are exchanged between the reservoir and the culture chamber by diffusion only. Using this capability, we verify that the mammospheres are enriched for tumor initiating cells by staining aldehyde dehydrogenase activity, a cancer stem cell marker. To the best of our knowledge, this is the first assay that enables the direct observation of tumor-initiating cells within a suspended mammosphere.
  Biomedical Microdevices 03/2013;
• Article: Towards an optimal and unbiased approach for tumor cell isolation.

  Bhuvanendran Nair Gourikutty Sajay, Chia-Pin Chang, Hamizah Ahmad, Wong Chee Chung, Poenar Daniel Puiu, Abdur Rub Abdur Rahman
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  ABSTRACT: Our current understanding of clinical significance or the lack thereof of circulating tumor cells (CTCs) is biased by the technology used to isolate these rare cells. Despite the presence of a vast number of academic and commercial technologies, the lack of a standardized and optimized platform has been widely noted. We present a negative enrichment approach, integrating WBC depletion and chemical-free RBC depletion in the same setup without the need for centrifugation, washing or multiple sample handling steps. This approach achieves an average of >90 % recovery of spiked tumor cells and >99 % total WBC depletion in whole blood across multiple cell lines, in a simple and easy-to-use assay. The results presented herein and ongoing improvements aim to fulfill the need for a highly reliable, unbiased, standardized, and optimized CTC isolation platform, using component technologies that are validated for cell isolation.
  Biomedical Microdevices 03/2013;
• Article: Fabrication of electro-microfluidic channel for single cell electroporation.

  Mehdi Shahini, Frans van Wijngaarden, John T W Yeow
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  ABSTRACT: The point of this paper is to demonstrate the use of a quick and cheap fabrication method to realize a laser-ablated microfluidic channel for single cell electroporation. Traditional lithography of microchannel with electrode in MEMS applications has always been complicated. Here, we introduce a new methodology of fabricating microchannel with electrical functionalities achieved through a fast and cheap process. In the present methodology, the microchannel pattern is cut out of polyimide, bonded to two ITO-coated substrates using Teflon as an adhesion layer. ITO as conductive material enables electric field in the channel and its optical transparency allows microscopy techniques to be utilized in characterizing the behavior of the microfluidic chip. The performance of the chip was tested on irreversible single-cell scale electroporation which requires relatively high voltages. CHO cells, as mammalian cells, were passed through the microchannel to experience electric field. Cells were loaded with a fluorogenic dye, Calcein AM, and the electroporation of each was individually recorded in real-time via fluorescent microscopy. The results show promising performance of the electric microchannel in electroporation. By customizing of ITO electrodes and the design of microchannel pattern, utilization and integration of the proposed electrical microchannel in variety of other MEMS-based devices are achievable.
  Biomedical Microdevices 03/2013;
• Article: The effects of annealing on mechanical, chemical, and physical properties and structural stability of Parylene C.

  Rene Patrick von Metzen, Thomas Stieglitz
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  ABSTRACT: Parylene C is one of the established encapsulation polymers for chronic implants. We investigated the influence of annealing Parylene C on its mechanical properties, chemical structure, and on the stability of Parylene C - platinum - Parylene C sandwich structures as a model of flexible neural interfaces in 0.9 % saline solution. Films of Parylene C were annealed at 200 °C, 300 °C, 350 °C, and 400 °C in nitrogen atmosphere. Temperatures of 350 °C and higher as well as annealing in air destroyed the Parylene C layers; films annealed at lower temperatures showed identical infrared spectra. Higher anneal temperatures produced increased values of elongation at break, tensile and yield strength, and yield strain while at the same time Young's modulus was shown to decrease. Crystallinity increased with annealing temperature. The structural stability of sandwich structures benefitted remarkably from annealing. Sandwich structures annealed at 300 °C maintained their structural integrity during 320 days in saline solution at 37 °C and the insulation capability stayed consistently high.
  Biomedical Microdevices 03/2013;
• Article: Monitoring systems and quantitative measurement of biomolecules for the management of Trauma.

  Christian N Kotanen, Anthony Guiseppi-Elie
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  ABSTRACT: Continued high morbidity and complications due to trauma related hemorrhage underscores the fact that our understanding of the detailed molecular events of trauma are inadequate to bring life-saving changes to practice. The current state of efficacy and advances in biomedical microdevice technology for trauma diagnostics concerning hemorrhage and hemorrhagic shock was considered with respect to vital signs and metabolic biomarkers. Tachycardia and hypotension are markers of hemorrhagic shock in decompensated trauma patients. Base deficit has been predicative of injury severity at hospital admission. Tissue oxygen saturation has been predicative of onset of multiple organ dysfunction syndrome. Blood potassium levels increase with onset of hemorrhagic shock. Lactate is a surrogate for tissue hypoxia and its clearance predicts mortality. Triage glucose measurements have been shown to be specific in predicting major injuries. No vital sign has yet to be proven effective as an independent predictor of trauma severity. Point of care (POC) devices allow for rapid results, easy sample preparation and processing, small sample volumes, small footprint, multifunctional analysis, and low cost. Advances in the field of in-vivo biosensors has provided a much needed platform by which trauma related metabolites can be monitored easily, rapidly and continuously. Multi-analyte monitoring biosensors have the potential to explore areas still undiscovered in the realm of trauma physiology.
  Biomedical Microdevices 03/2013;
• Article: Microfluidic based immunosensor for detection and purification of carbonylated proteins.

  Hui Xia, Bobby Mathew, Tom John, Hisham Hegab, June Feng
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  ABSTRACT: A microchip has been developed on the basis of immno-precipitation approach for fast and sensitive enrichment of low abundant carbonylated proteins. This microfluidic method could enrich molecular biomarkers, which could be further analyzed in the proteomic study of age-related diseases and therapeutic development. In this study, an immunoaffinity-based PDMS micro-device was designed, fabricated, and chemically modified to specifically trap DNP-labeled PTM proteins of low abundance from a complex protein mixture. Carbonylated protein is selected as a representative PTM protein to illustrate the wide application of this immuno-based microchip for other PTMs which could be readily labeled by different antibody groups. Surface characterization methods such as atomic force microscopy and fluorescence microscopy were used to evaluate the construction of glutaraldehyde- and antibody- terminated PDMS substrates in the device fabrication. Quantitative study was also applied to study the target protein capture and elution efficiency of the device. In a testing mixture consisting of smaller amount of test model-In Vitro oxidized cytochrome c and large blocking protein BSA, a high sensitivity and specificity for only carbonylated protein biomarkers was demonstrated using this on-chip immnuoaffinity based extraction/enrichment. For this highly dense 193-post arrays μ-chip, a low abundance of 159 ng of standard in vitro test model- cytochrome c was enriched at flow speed of 5 μL/min within 110 min. We demonstrated that this nascent micro-immunoprecipitation (μ-IP) method is capable for enrichment of biomarkers in protein post-translation modification related diseases and promise great advance in early disease detection.
  Biomedical Microdevices 03/2013;