Biomedical Microdevices (BIOMED MICRODEVICES)

Publications in this journal

• Article: Novel disposable biochip platform employing supercritical angle fluorescence for enhanced fluorescence collection

  Duncan Hill, Barry McDonnell, Stephen Hearty, Lourdes Basabe-Desmonts, Robert Blue, Michal Trnavsky, Colm McAtamney, Richard O’Kennedy, Brian D. MacCraith
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  ABSTRACT: This paper presents an overview of development of a novel disposable plastic biochip for multiplexed clinical diagnostic applications. The disposable biochip is manufactured using a low-cost, rapid turn- around injection moulding process and consists of nine parabolic elements on a planar substrate. The optical elements are based on supercritical angle fluorescence (SAF) which provides substantial enhancement of the fluorescence collection efficiency but also confines the fluorescence detection volume strictly to the immediate proximity of the biochip surface, thereby having the potential to discriminate against background fluorescence from the analyte solution. An optical reader is also described that enables interrogation and fluorescence collection from the nine optical elements on the chip. The sensitivity of the system was determined with a biotin-avidin assay while its clinical utility was demonstrated in an assay for C-reactive protein (CRP), an inflammation marker. KeywordsLab on a chip–Supercritical angle fluorescence–Immunoassay–Cardiac marker
  Biomedical Microdevices 04/2012; 13(4):759-767.
• Article: Laser ablation of micropores for formation of artificial planar lipid bilayers

  Thomas J. O’Shaughnessy, Jenny E. Hu, John L. Kulp, Susan M. Daly, Frances S. Ligler
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  ABSTRACT: Artificial lipid bilayers are a powerful tool for studying synthetic or reconstituted ion channels. Key to forming these lipid bilayers is having a small aperture in a septum separating two solution chambers. Traditional methods of aperture generation involve manually punching the aperture into the septum. While these techniques work, they are difficult to implement reliably and do not produce consistently sized apertures. Presented here is a method of using a UV excimer laser with a nanosecond scale pulse width to laser ablate apertures from 4 to 105μm in 20μm thick polycarbonate films for use in artificial lipid bilayer experiments. The data demonstrate that the apertures produced by laser ablation are highly reproducible and can support both the formation of stable, long-lasting lipid bilayers as well as the recording of ion channels incorporated into the bilayers.
  Biomedical Microdevices 04/2012; 9(6):863-868.
• Article: Continuous high-throughput phosphopeptide enrichment using microfluidic channels modified with aligned ZnO/TiO2 nanorod arrays

  Zhongyuan He, Qinghong Zhang, Hongzhi Wang, Yaogang Li
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  ABSTRACT: A capillary microchannel (CM) containing TiO2-coated ZnO nanorod arrays was applied as a novel microfluidic device to selectively bind and enrich phosphopeptides. The device was prepared by pumping a TiO2 sol into a CM containing preformed ZnO nanorod arrays. Different thicknesses of the TiO2 coating were obtained by controlling the flow duration of TiO2 sol. The modified CM achieved uninterrupted high-throughput introduction, capture and enrichment of phosphopeptides using continuous-flow operation. The microfluidic device based on the modified CM showed great selectivity, sensitivity and durability for the enrichment of phosphopeptides from tryptic protein digests. These results suggest that microfluidic chips employing this strategy can be used for rapid and high-throughput enrichment of phosphopeptides from complex mixtures. KeywordsMicrofluidic device–TiO2/ZnO nanorod arrays–Phosphopeptide enrichment–Continuous-flow–High-throughput–Nanobiotechnology
  Biomedical Microdevices 04/2012; 13(5):865-875.
• Article: An automated micro-solid phase extraction device involving integrated \high-pressure microvalves for genetic sample preparation

  Song-I Han, Ki-Ho Han, A. Bruno Frazier, Jerome P. Ferrance, James P. Landers
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  ABSTRACT: This paper presents an automated micro-SPE device for DNA extraction using monolithically integrated high-pressure microvalves. The automated micro-SPE device was fabricated through glass-to-glass thermal bonding and microfluidic system interface technologies. To increase the DNA extraction efficiency, silica beads were packed in the extraction microchannel involving two weir structures. Experimental results show that the DNA extraction efficiency using the automated micro-SPE device containing bare silica beads was 75.87% in the first 8μl of solution eluted by automated SPE procedure. In addition, the reproducibility of the DNA extraction was evaluated by ten successive measurements. Genomic DNA extracted from human WBCs had an absorbance ratio of DNA to protein (A260/A280) of 1.56. The applicability of this automated micro-SPE device to genetic sample preparation was verified by PCR amplification of a β-globulin gene using the genomic DNA extracted from WBCs. Consequently, we demonstrated that the proposed automatic micro-SPE device can extract nucleic acids from biological samples, thereby facilitating its integration with downstream genetic analyses in a micro format.
  Biomedical Microdevices 04/2012; 11(4):935-942.
• Article: Mass producible and biocompatible microneedle patch and functional verification of its usefulness for transdermal drug delivery

  Chun Yan Jin, Man Hee Han, Seung S. Lee, Yo Han Choi
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  ABSTRACT: The key issues in the development of a microneedle patch as a tool for transdermal drug delivery are safety and delivery performance in addition to economical production. In this paper, novel fabrication methods for an inexpensive microneedle patch made of biocompatible polymer are reported, along with functional verifications for the fabricated microneedle patch through animal models. We combined the merits of in-line microneedles, i.e., easy and economical production, with the superior performance of two-dimensionally arrayed microneedles. One-dimensionally fabricated microneedles were assembled to make two-dimensionally arrayed patches to attain our goal. First, we fabricated strips with one-dimensionally arrayed microneedles through deep X-ray lithography on polymethylmethacrylate or another negative photoresist, SU-8, with sharply reduced exposure time. Second, we assembled microneedle strips to make two-dimensionally arrayed microneedles, which we utilized further for fabrication of molding masters. Finally, we prepared microneedle patches made of polycarbonate by hot embossing with these masters. We then demonstrated the actual delivery of exogenous materials through application on skin via animal experiments, and we found no detectable side effects such as inflammation or allergic reactions at the site of application.
  Biomedical Microdevices 04/2012; 11(6):1195-1203.
• Article: A microperfused incubator for tissue mimetic 3D cultures

  Jelena Vukasinovic, D. Kacy Cullen, Michelle C. LaPlaca, Ari Glezer
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  ABSTRACT: High density, three-dimensional (3D) cultures present physical similarities to in vivo tissue and are invaluable tools for pre-clinical therapeutic discoveries and development of tissue engineered constructs. Unfortunately, the use of dense cultures is hindered by intra-culture transport limits allowing just a few layer thick cultures for reproducible studies. In order to overcome diffusion limits in intra-culture nutrient and gas availability, a simple scalable microfluidic perfusion platform was developed and validated. A novel perfusion approach maintained laminar flow of nutrients through the culture to meet metabolic need, while removing depleted medium and catabolites. Velocity distributions and 3D flow patterns were measured using microscopic particle image velocimetry. The effectiveness of forced convection laminar perfusion was confirmed by culturing 700 µm thick neural-astrocytic (1:1) constructs at cell density approaching that of the brain (50,000 cells/mm3). At the optimized flow rate of the nutrient medium, the culture viability reached 90% through the full construct thickness at 2days of perfusion while unperfused controls exhibited widespread cell death. The membrane aerated perfusion platform was integrated within a miniature, imaging accessible enclosure enabling temperature and gas control of the culture environment. Temperature measurements demonstrated fast feedback response to environmental changes resulting in the maintenance of the physiological temperature within 37 ± 0.2°C. Reproducible culturing of tissue equivalents within dynamically controlled environments will provide higher fidelity to in vivo function in an in vitro accessible format for cell-based assays and regenerative medicine.
  Biomedical Microdevices 04/2012; 11(6):1155-1165.
• Source

  Available from: libna.mntl.illinois.edu

  Article: Lipid bilayer coated Al2O3 nanopore sensors: towards a hybrid biological solid-state nanopore

  Bala Murali Venkatesan, James Polans, Jeffrey Comer, Supriya Sridhar, David Wendell, Aleksei Aksimentiev, Rashid Bashir
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  ABSTRACT: Solid-state nanopore sensors are highly versatile platforms for the rapid, label-free electrical detection and analysis of single molecules, applicable to next generation DNA sequencing. The versatility of this technology allows for both large scale device integration and interfacing with biological systems. Here we report on the development of a hybrid biological solid-state nanopore platform that incorporates a highly mobile lipid bilayer on a single solid-state Al2O3 nanopore sensor, for the potential reconstitution of ion channels and biological nanopores. Such a system seeks to combine the superior electrical, thermal, and mechanical stability of Al2O3 solid-state nanopores with the chemical specificity of biological nanopores. Bilayers on Al2O3 exhibit higher diffusivity than those formed on TiO2 and SiO2 substrates, attributed to the presence of a thick hydration layer on Al2O3, a key requirement to preserving the biological functionality of reconstituted membrane proteins. Molecular dynamics simulations demonstrate that the electrostatic repulsion between the dipole of the DOPC headgroup and the positively charged Al2O3 surface may be responsible for the enhanced thickness of this hydration layer. Lipid bilayer coated Al2O3 nanopore sensors exhibit excellent electrical properties and enhanced mechanical stability (GΩ seals for over 50h), making this technology ideal for use in ion channel electrophysiology, the screening of ion channel active drugs and future integration with biological nanopores such as α-hemolysin and MspA for rapid single molecule DNA sequencing. This technology can find broad application in bio-nanotechnology. KeywordsNanopore–Al2O3 –Lipid bilayer–Hybrid biological solid-state Nanopore
  Biomedical Microdevices 04/2012; 13(4):671-682.
• Article: Microfluidic sedimentation cytometer for milk quality and bovine mastitis monitoring

  Jose L. Garcia-Cordero, Louise M. Barrett, Richard O’Kennedy, Antonio J. Ricco
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  ABSTRACT: We report a rapid, low-cost, portable microfluidic sedimentation cytometer (SeCy) for assessing the somatic cell count and fat content of milk in 15min using a “sample-in, answer-out” approach. The system consists of 12 independent microfluidic devices, essentially flattened funnel structures, fabricated on the footprint of a single plastic compact disc (CD). Each funnel structure holds 150μL of milk, has an inlet for milk filling and an outlet for air to escape, and ends in a narrow, closed-end microfluidic channel that facilitates packing of the cells into a column whose length is proportional to cell count. The closed-end channel provides accurate cell counts over the range 50,000–>3,000,000 cells per mL. The assay separates cells and fat globules based on their densities (by differential sedimentation), concentrating white cells in the closed-end channel near the outer rim of the CD for estimation of total “cell pellet” volume, while fat globules move toward the center of disc rotation, forming a fat “band” in the funnel. After adding milk to two or more microfluidic devices, the CD is loaded onto a custom-built reader unit that spins the disc for 15min. Two low-cost microscopes in the reader image the centrifuged cell pellet and the fat band, providing a sufficiently accurate cell count to diagnose mastitis and measuring fat content as an indication of health and nutritional status. KeywordsBovine mastitis-Milk-Cytometer-Centrifugal microfluidics-Sedimentation-Cell-counter-Somatic cells-Sample-to-answer device
  Biomedical Microdevices 04/2012; 12(6):1051-1059.
• Source

  Available from: nanoarchive.org

  Article: Interdigitated microelectrode array-coupled bipolar semiconductor photodiode array (IMEA-PDA) microchip for on-chip electrochemiluminescence detection

  Sukdeb Pal, Min Jung Kim, Yu Kyung Tak, Ho Taik Kwon, Joon Myong Song
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  ABSTRACT: This paper reports the design, fabrication and testing of a microchip wherein interdigitated microelectrode arrays (IMEA) were integrated with bipolar semiconductor photodiode array (PDA) chip to fabricate a highly compact embodiment for on-chip handling of solutions and electrochemiluminescence (ECL) detection. A 12 × 12 micro array of photodiodes, each coupled with an interdigitated microelectrode array (IMEA), an array of current amplifiers, and a photodiode element-addressing circuit were integrated into a single 2 × 2 cm2 IC chip. Each photodiode had dimensions of 300 × 300 μm2 and the photodiode-to-photodiode distance was 100 μm. The chip was successfully applied to the on-chip quantification of electro-chemiluminescing probe-labeled single stranded oligonucleotides. The minimum detectable limit at signal/noise ≥ 3 was found to be 5 × 10−14 moles of oligonucleotides with a sample volume as low as 5 µl (i.e., 10fmole/μl). The attractive features of the developed IMEA-PDA microchip are that a plurality of samples can be analyzed simultaneously using a chip and that for a given sample the data can be averaged from values obtained from multiple, individually addressed pixels. These in turn bring in speed and statistical confidence in analysis. The IMEA-PDA microchip system has the potential to be used as a versatile and highly compact chemical analysis tool for chemical sensing and metrology applications.
  Biomedical Microdevices 04/2012; 11(5):971-980.
• Source

  Available from: swansea.ac.uk

  Article: Nanotechnology for regenerative medicine

  Dongwoo Khang, Joseph Carpenter, Young Wook Chun, Rajesh Pareta, Thomas J. Webster
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  ABSTRACT: Future biomaterials must simultaneously enhance tissue regeneration while minimizing immune responses and inhibiting infection. While the field of tissue engineering has promised to develop materials that can promote tissue regeneration for the entire body, such promises have not become reality. However, tissue engineering has experienced great progress due to the recent emergence of nanotechnology. Specifically, it has now been well established that increased tissue regeneration can be achieved on almost any surface by employing novel nano-textured surface features. Numerous studies have reported that nanotechnology accelerates various regenerative therapies, such as those for the bone, vascular, heart, cartilage, bladder and brain tissue. Various nano-structured polymers and metals (alloys) have been investigated for their bio (and cyto) compatibility properties. This review paper discusses several of the latest nanotechnology findings in regenerative medicine (also now called nanomedicine) as well as their relative levels of success. KeywordsNanotechnology-Tissue engineering-Orthopedic-Vascular-Neural-Skin-Cellular and protein interactions
  Biomedical Microdevices 04/2012; 12(4):575-587.
• Source

  Available from: wisc.edu

  Article: Sperm motion in a microfluidic fertilization device

  M. d. C. Lopez-Garcia, R. L. Monson, K. Haubert, M. B. Wheeler, D. J. Beebe
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  ABSTRACT: Microfluidics has shown promise as a new platform for assisted reproduction. To assess the potential of microfluidics for fertilization, we studied sperm and fluid motion in microchannels to better understand the flow characteristics in a microfluidic device, how sperm interacted with this flow, and how sperm–oocyte attachment occurs in the device. There is a threshold fluid velocity where sperm transition from traveling with the fluid to a regime in which the sperm can move independently of the flow. A significant population of sperm remained in the inlet well area. Based on the lack of progressive forward movement, it was presumed that these sperm may have defects. Also of extreme interest was the tendency of sperm to travel along surface contours. These observations provide an improved understanding of sperm motion in microchannels and provide a basis for improved device designs that take advantage of the sperm/flow and sperm/geometry interactions.
  Biomedical Microdevices 04/2012; 10(5):709-718.
• Article: An agarose-based microfluidic platform with a gradient buffer for 3D chemotaxis studies

  Ulrike Haessler, Yevgeniy Kalinin, Melody A. Swartz, Mingming Wu
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  ABSTRACT: The current state-of-art in 3D microfluidic chemotaxis device (μFCD) is limited by the inherent coupling of the fluid flow and chemical concentration gradients. Here, we present an agarose-based 3D μFCD that decouples these two important parameters, in that the flow control channels are separated from the cell compartment by an agarose gel wall. This decoupling is enabled by the transport property of the agarose gel, which—in contrast to the conventional microfabrication material such as polydimethylsiloxane (PDMS)—provides an adequate physical barrier for convective fluid flow while at the same time readily allowing protein diffusion. We demonstrate that in this device, a gradient can be pre-established in an agarose layer above the cell compartment (a gradient buffer) before adding the 3D cell-containing matrix, and the dextran (10kDa) concentration gradients can be re-established within 10min across the cell-containing matrix and remain stable indefinitely. We successfully quantified the chemotactic response of murine dendritic cells to a gradient of CCL19, an 8.8kDa lymphoid chemokine, within a type I collagen matrix. This model system is easy to set up, highly reproducible, and will benefit research on 3D chemoinvasion studies, for example with cancer cells or immune cells. Because of its gradient buffering capacity, it is particularly suitable for studying rapidly migrating cells like mature dendritic cells and neutrophils.
  Biomedical Microdevices 04/2012; 11(4):827-835.
• Article: Ultraminiature encapsulated accelerometers as a fully implantable sensor for implantable hearing aids

  Woo-Tae Park, Kevin N. O’Connor, Kuan-Lin Chen, Joseph R. Mallon, Toshiki Maetani, Parmita Dalal, Rob N. Candler, Vipin Ayanoor-Vitikkate, Joseph B. Roberson, Sunil Puria, Thomas W. Kenny
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  ABSTRACT: Experiments were conducted to evaluate a silicon accelerometer as an implantable sound sensor for implantable hearing aids. The main motivation of this study is to find an alternative sound sensor that is implantable inside the body, yet does not suffer from the signal attenuation from the body. The merit of the accelerometer sensor as a sound sensor will be that it will utilize the natural mechanical conduction in the middle ear as a source of the vibration. With this kind of implantable sound sensor, a totally implantable hearing aid is feasible. A piezoresistive silicon accelerometer that is completely encapsulated with a thin silicon film and long flexible flex-circuit electrical cables were used for this study. The sensor is attached on the middle ear ossicles and measures the vibration transmitted from the tympanic membrane due to the sound in the ear canal. In this study, the sensor is fully characterized on a human cadaveric temporal bone preparation.
  Biomedical Microdevices 04/2012; 9(6):939-949.
• Article: A uniaxial bioMEMS device for imaging single cell response during quantitative force-displacement measurements.

  David B Serrell, Jera Law, Andrew J Slifka, Roop L Mahajan, Dudley S Finch
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  ABSTRACT: A microfabricated device has been developed for imaging of a single, adherent cell while quantifying force under an applied displacement. The device works in a fashion similar to that of a displacement-controlled uniaxial tensile machine. The device was calibrated using a tipless atomic force microscope (AFM) cantilever and shows excellent agreement with the calculated spring constant. A step input was applied to a single, adherent fibroblast cell and the viscoelastic response was characterized with a mechanical model. The adherent fibroblast was imaged by use of epifluorescence and phase contrast techniques.
  Biomedical Microdevices 12/2008; 10(6):883-9.
• Article: Design of MEMS devices with optical apertures for the detection of transparent biological cells

  Xiaodong Zhou, Daniel Puiu Poenar, Kai Yu Liu, Man Siu Tse, Chew-Kiat Heng, Swee Ngin Tan
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  ABSTRACT: This paper provides a novel technique to detect transparent biological living cells trapped in a microfluidic MEMS device by optical diffraction. The device essentially consists of an optical aperture or an aperture array patterned in metal layer and a microfluidic chamber positioned above the center of the aperture. When the cells in the chamber are illuminated through the aperture, the far-field diffraction pattern can be recorded by a CCD camera or a photodetector array. This diffraction pattern uniquely corresponds to the sizes, positions, and intrinsic optical properties of the aperture, cells, and the microfluidic chamber materials, so any unknown but relevant parameter is able to be extrapolated when all other parameters are fixed or identified. This paper describes in detail the designs of various microfluidic chambers and apertures for this application, and the development of a complete set of software for the analysis of the cells’ optical properties. Compared with other currently available methods for the detection of transparent living cells, this method has the advantages of simple device structure, easy to manipulate, able to simultaneously detect several cells of different species, as well as providing accurate and sensitive results. Besides the detection of living cells, this technique can also be used to detect or characterize other transparent or low optical absorption particles, such as polymer spheres or insoluble droplets, inside an aqueous solution.
  Biomedical Microdevices 09/2008; 10(5):639-652.
• Article: An in silico bioreactor for simulating laboratory experiments in tissue engineering.

  Fabio Galbusera, Margherita Cioffi, Manuela T Raimondi
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  ABSTRACT: This paper presents a software framework for the computational modeling of tissue engineering experiments, aimed to supplement and extend the empirical techniques currently employed in tissue engineering. The code included a model of cell population dynamics coupled to a finite element model of oxygen diffusion and consumption at the macroscale level, including the scaffold and the culture medium, and at the level of the scaffold microarchitecture. Cells were modeled as discrete entities moving in a continuum space, under the action of adhesion and repulsion forces. Oxygen distribution was calculated with the transient diffusion equation; oxygen consumption by cells was modeled by using the Michaelis-Menten equation. Other phenomena that can be formulated as a differential problem could be added in a straightforward manner to the code, due to the use of a general purpose finite element library. Two scaffold geometries were considered: a fiber scaffold and a scaffold with interconnected spherical pores. Cells were predicted to form clusters and adhere to the scaffold walls. Although the code demonstrated the ability to provide a robust performance, a calibration of the parameters employed in the model, based on specific laboratory experiments, is now required to verify the reliability of the results.
  Biomedical Microdevices 09/2008; 10(4):547-54.