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Top 20 Most Cited Articles
The 20 most cited articles over time based on CrossRef data.
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Biomicrofluidics 1, 021503 (2007); http://dx.doi.org/10.1063/1.2723669 (15 pages) | Cited 74 times Online Publication Date: 10 May 2007
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Multi-target pathogen detection using heterogeneous medical samples require continuous filtering, sorting, and trapping of debris, bioparticles, and immunocolloids within a diagnostic chip. We present an integrated AC dielectrophoretic (DEP) microfluidic platform based on planar electrodes that form three-dimensional (3D) DEP gates. This platform can continuously perform these tasks with a throughput of 3 μL/min. Mixtures of latex particles, Escherichia coli Nissle, Lactobacillus, and Candida albicans are sorted and concentrated by these 3D DEP gates. Surface enhanced Raman scattering is used as an on-chip detection method on the concentrated bacteria. A processing rate of 500 bacteria was estimated when 100 μl of a heterogeneous colony of 107 colony forming units /ml was processed in a single pass within 30 min.
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Ultrafast microfluidics using surface acoustic waves Biomicrofluidics 3, 012002 (2009); http://dx.doi.org/10.1063/1.3056040 (23 pages) | Cited 49 times Online Publication Date: 2 January 2009
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We demonstrate that surface acoustic waves (SAWs), nanometer amplitude Rayleigh waves driven at megahertz order frequencies propagating on the surface of a piezoelectric substrate, offer a powerful method for driving a host of extremely fast microfluidic actuation and micro/bioparticle manipulation schemes. We show that sessile drops can be translated rapidly on planar substrates or fluid can be pumped through microchannels at 1–10 cm/s velocities, which are typically one to two orders quicker than that afforded by current microfluidic technologies. Through symmetry-breaking, azimuthal recirculation can be induced within the drop to drive strong inertial microcentrifugation for micromixing and particle concentration or separation. Similar micromixing strategies can be induced in the same microchannel in which fluid is pumped with the SAW by merely changing the SAW frequency to rapidly switch the uniform through-flow into a chaotic oscillatory flow by exploiting superpositioning of the irradiated sound waves from the sidewalls of the microchannel. If the flow is sufficiently quiescent, the nodes of the transverse standing wave that arises across the microchannel also allow for particle aggregation, and hence, sorting on nodal lines. In addition, the SAW also facilitates other microfluidic capabilities. For example, capillary waves excited at the free surface of a sessile drop by the SAW underneath it can be exploited for micro/nanoparticle collection and sorting at nodal points or lines at low powers. At higher powers, the large accelerations off the substrate surface as the SAW propagates across drives rapid destabilization of the drop free surface giving rise to inertial liquid jets that persist over 1–2 cm in length or atomization of the entire drop to produce 1–10 μm monodispersed aerosol droplets, which can be exploited for ink-jet printing, mass spectrometry interfacing, or pulmonary drug delivery. The atomization of polymer/protein solutions can also be used for the rapid synthesis of 150–200 nm polymer/protein particles or biodegradable polymeric shells in which proteins, peptides, and other therapeutic molecules are encapsulated within for controlled release drug delivery. The atomization of thin films behind a translating drop containing polymer solutions also gives rise to long-range spatial ordering of regular polymer spots whose size and spacing are dependent on the SAW frequency, thus offering a simple and powerful method for polymer patterning without requiring surface treatment or physical/chemical templating.
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Review Article—Dielectrophoresis: Status of the theory, technology, and applications Biomicrofluidics 4, 022811 (2010); http://dx.doi.org/10.1063/1.3456626 (35 pages) | Cited 46 times Online Publication Date: 29 June 2010
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A review is presented of the present status of the theory, the developed technology and the current applications of dielectrophoresis (DEP). Over the past 10 years around 2000 publications have addressed these three aspects, and current trends suggest that the theory and technology have matured sufficiently for most effort to now be directed towards applying DEP to unmet needs in such areas as biosensors, cell therapeutics, drug discovery, medical diagnostics, microfluidics, nanoassembly, and particle filtration. The dipole approximation to describe the DEP force acting on a particle subjected to a nonuniform electric field has evolved to include multipole contributions, the perturbing effects arising from interactions with other cells and boundary surfaces, and the influence of electrical double-layer polarizations that must be considered for nanoparticles. Theoretical modelling of the electric field gradients generated by different electrode designs has also reached an advanced state. Advances in the technology include the development of sophisticated electrode designs, along with the introduction of new materials (e.g., silicone polymers, dry film resist) and methods for fabricating the electrodes and microfluidics of DEP devices (photo and electron beam lithography, laser ablation, thin film techniques, CMOS technology). Around three-quarters of the 300 or so scientific publications now being published each year on DEP are directed towards practical applications, and this is matched with an increasing number of patent applications. A summary of the US patents granted since January 2005 is given, along with an outline of the small number of perceived industrial applications (e.g., mineral separation, micropolishing, manipulation and dispensing of fluid droplets, manipulation and assembly of micro components). The technology has also advanced sufficiently for DEP to be used as a tool to manipulate nanoparticles (e.g., carbon nanotubes, nano wires, gold and metal oxide nanoparticles) for the fabrication of devices and sensors. Most efforts are now being directed towards biomedical applications, such as the spatial manipulation and selective separation/enrichment of target cells or bacteria, high-throughput molecular screening, biosensors, immunoassays, and the artificial engineering of three-dimensional cell constructs. DEP is able to manipulate and sort cells without the need for biochemical labels or other bioengineered tags, and without contact to any surfaces. This opens up potentially important applications of DEP as a tool to address an unmet need in stem cell research and therapy.
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Real-time detection, control, and sorting of microfluidic droplets Biomicrofluidics 1, 044101 (2007); http://dx.doi.org/10.1063/1.2795392 (12 pages) | Cited 29 times Online Publication Date: 3 October 2007
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We report the design and implementation of capacitive detection and control of microfluidic droplets in microfluidic devices. Integrated microfluidic chip(s) with detection/control circuit enables us to monitor in situ the individual volume of droplets, ranging from nanoliter to picoliter, velocity and even composition, with an operation frequency of several kilohertz. Through electronic feedback, we are able to easily count, sort, and direct the microfluidic droplets. Potential applications of this approach can be employed in the areas of biomicrofluidic processing, microchemical reactions as well as digital microfluidics.
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Biomicrofluidics 2, 034105 (2008); http://dx.doi.org/10.1063/1.2973661 (11 pages) | Cited 29 times Online Publication Date: 11 August 2008
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The conventional microfluidic H filter is modified with multi-insulating blocks to achieve a flow-through manipulation and separation of microparticles. The device transports particles by exploiting electro-osmosis and electrophoresis, and manipulates particles by utilizing dielectrophoresis (DEP). Polydimethylsiloxane (PDMS) blocks fabricated in the main channel of the PDMS H filter induce a nonuniform electric field, which exerts a negative DEP force on the particles. The use of multi-insulating blocks not only enhances the DEP force generated, but it also increases the controllability of the motion of the particles, facilitating their manipulation and separation. Experiments were conducted to demonstrate the controlled flow direction of particles by adjusting the applied voltages and the separation of particles by size under two different input conditions, namely (i) a dc electric field mode and (ii) a combined ac and dc field mode. Numerical simulations elucidate the electrokinetic and hydrodynamic forces acting on a particle, with theoretically predicted particle trajectories in good agreement with those observed experimentally. In addition, the flow field was obtained experimentally with fluorescent tracer particles using the microparticle image velocimetry (μ-PIV) technique.
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Biomicrofluidics 1, 044102 (2007); http://dx.doi.org/10.1063/1.2818767 (5 pages) | Cited 28 times Online Publication Date: 27 November 2007
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We report an interesting buffer electric relaxation time tuning technique, coupled with a glutaraldehyde cross-linking cell fixation reaction, which allows for sensitive dielectrophoretic analysis and discrimination of bovine red blood cell (bRBC) starvation age. The buffer composition is selected such that two easily accessible dielectrophoretic crossover frequencies (cof) exist. Low concentration glutaraldehyde fixation was observed to produce a threefold decrease in the higher cof with a comparable increase in the lower cof also witnessed. More importantly, increased glutaraldehyde fixation concentration significantly increased the higher cof by a factor found to be sensitive to the bRBC starvation age.
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Understanding electrokinetics at the nanoscale: A perspective Biomicrofluidics 3, 012001 (2009); http://dx.doi.org/10.1063/1.3056045 (15 pages) | Cited 23 times Online Publication Date: 2 January 2009
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Electrokinetics promises to be the microfluidic technique of choice for portable diagnostic chips and for nanofluidic molecular detectors. However, despite two centuries of research, our understanding of ion transport and electro-osmotic flow in and near nanoporous membranes, whose pores are natural nanochannels, remains woefully inadequate. This short exposition reviews the various ion-flux and hydrodynamic anomalies and speculates on their potential applications, particularly in the area of molecular sensing. In the process, we revisit several old disciplines, with some unsolved open questions, and we hope to create a new one.
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Biomicrofluidics 2, 024103 (2008); http://dx.doi.org/10.1063/1.2930817 (14 pages) | Cited 19 times Online Publication Date: 6 May 2008
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In this paper, we demonstrate for the first time that insulative dielectrophoresis can induce size-dependent trajectories of DNA macromolecules. We experimentally use λ (48.5 kbp) and T4GT7 (165.6 kbp) DNA molecules flowing continuously around a sharp corner inside fluidic channels with a depth of 0.4 μm. Numerical simulation of the electrokinetic force distribution inside the channels is in qualitative agreement with our experimentally observed trajectories. We discuss a possible physical mechanism for the DNA polarization and dielectrophoresis inside confining channels, based on the observed dielectrophoresis responses due to different DNA sizes and various electric fields applied between the inlet and the outlet. The proposed physical mechanism indicates that further extensive investigations, both theoretically and experimentally, would be very useful to better elucidate the forces involved at DNA dielectrophoresis. When applied for size-based sorting of DNA molecules, our sorting method offers two major advantages compared to earlier attempts with insulative dielectrophoresis: Its continuous operation allows for high-throughput analysis, and it only requires electric field strengths as low as ∼ 10 V/cm.
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Electrokinetic focusing and filtration of cells in a serpentine microchannel Biomicrofluidics 3, 044109 (2009); http://dx.doi.org/10.1063/1.3267098 (10 pages) | Cited 19 times Online Publication Date: 24 November 2009
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Focusing cells into a single stream is usually a necessary step prior to counting and separating them in microfluidic devices such as flow cytometers and cell sorters. This work presents a sheathless electrokinetic focusing of yeast cells in a planar serpentine microchannel using dc-biased ac electric fields. The concurrent pumping and focusing of yeast cells arise from the dc electrokinetic transport and the turn-induced ac/dc dielectrophoretic motion, respectively. The effects of electric field (including ac to dc field ratio and ac field frequency) and concentration (including buffer concentration and cell concentration) on the cell focusing performance were studied experimentally and numerically. A continuous electrokinetic filtration of E. coli cells from yeast cells was also demonstrated via their differential electrokinetic focusing in a serpentine microchannel.
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Design and integration of an all-in-one biomicrofluidic chip Biomicrofluidics 2, 034103 (2008); http://dx.doi.org/10.1063/1.2966453 (8 pages) | Cited 18 times Online Publication Date: 21 July 2008
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We demonstrate a highly integrated microfluidic chip with the function of DNA amplification. The integrated chip combines giant electrorheological-fluid actuated micromixer and micropump with a microheater array, all formed using soft lithography. Internal functional components are based on polydimethylsiloxane (PDMS) and silver/carbon black-PDMS composites. The system has the advantages of small size with a high degree of integration, high polymerase chain reaction efficiency, digital control and simple fabrication at low cost. This integration approach shows promise for a broad range of applications in chemical synthesis and biological sensing/analysis, as different components can be combined to target desired functionalities, with flexible designs of different microchips easily realizable through soft lithography.
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Biomicrofluidics 1, 014106 (2007); http://dx.doi.org/10.1063/1.2710191 (13 pages) | Cited 16 times Online Publication Date: 16 February 2007
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Rapid concentration and detection of bacteria in integrated chips and microfluidic devices is needed for the advancement of lab-on-a-chip devices because current detection methods require high concentrations of bacteria which render them impractical. We present a new chip-scale rapid bacteria concentration technique combined with surface-enhanced Raman scattering (SERS) to enhance the detection of low bacteria count samples. This concentration technique relies on convection by a long-range converging vortex to concentrate the bacteria into a packed mound of 200 μm in diameter within 15 min. Concentration of bioparticle samples as low as 104 colony forming units (CFU)/ml are presented using batch volumes as large as 150 μl. Mixtures of silver nanoparticles with Saccharomyces cerevisiae, Escherichia coli F-amp, and Bacillus subtilis produce distinct and noticeably different Raman spectra, illustrating that this technique can be used as a detection and identification tool.
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Long-range and superfast trapping of DNA molecules in an ac electrokinetic funnel Biomicrofluidics 2, 044103 (2008); http://dx.doi.org/10.1063/1.3037326 (10 pages) | Cited 16 times Online Publication Date: 5 December 2008
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In this work we report a microfluidic platform capable of trapping and concentrating a trace amount of DNA molecules efficiently. Our strategy invokes nonlinear electro-osmotic flow induced by charge polarization under high-frequency ac fields. With the asymmetric quadrupole electrode design, a unique converging flow structure can be created for generating focusing effects on DNA molecules. This focusing in turn transforms into a robust funnel that can collect DNA molecules distantly from the bulk and pack them into a compact cone with the aid of short-range dipole-induced self-attraction and dielectrophoresis. Our results reveal that not only can DNA molecules be concentrated within just a few seconds, but also they can be focused into threads of 1 mm in length, demonstrating the superfast and long-range trapping capability of this funnel. In addition, pico M DNA solutions can be concentrated with several decades of enhancement without any continuous feeding. Alternating concentration and release of DNA molecules is also illustrated, which has potentials in concentrating and transporting biomolecules in a continuous fashion using microdevices.
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Enhanced discrimination of normal oocytes using optically induced pulling-up dielectrophoretic force Biomicrofluidics 3, 014103 (2009); http://dx.doi.org/10.1063/1.3086600 (10 pages) | Cited 14 times Online Publication Date: 17 February 2009
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We present a method to discriminate normal oocytes in an optoelectrofluidic platform based on the optically induced positive dielectrophoresis (DEP) for in vitro fertilization. By combining the gravity with a pulling-up DEP force that is induced by dynamic image projected from a liquid crystal display, the discrimination performance could be enhanced due to the reduction in friction force acting on the oocytes that are relatively large and heavy cells being affected by the gravity field. The voltage condition of 10 V bias at 1 MHz was applied for moving normal oocytes. The increased difference of moving velocity between normal and starved abnormal oocytes allows us to discriminate the normal ones spontaneously under the moving image pattern. This approach can be useful to develop an automatic and interactive selection tool of fertilizable oocytes.
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Biomicrofluidics 3, 012007 (2009); http://dx.doi.org/10.1063/1.3098963 (14 pages) | Cited 14 times Online Publication Date: 23 March 2009
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This paper reviews the design and fabrication of polydimethylsiloxane (PDMS)-based conducting composites and their applications in microfluidic chip fabrication. Owing to their good electrical conductivity and rubberlike elastic characteristics, these composites can be used variously in soft-touch electronic packaging, planar and three-dimensional electronic circuits, and in-chip electrodes. Several microfluidic components fabricated with PDMS-based composites have been introduced, including a microfluidic mixer, a microheater, a micropump, a microdroplet controller, as well as an all-in-one microfluidic chip.
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Microfluidic blood plasma separation via bulk electrohydrodynamic flows Biomicrofluidics 1, 014103 (2007); http://dx.doi.org/10.1063/1.2409629 (13 pages) | Cited 13 times Online Publication Date: 20 December 2006
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An effective mechanism for rapid and efficient microfluidic particle trapping and concentration is proposed without requiring any mechanically moving parts. When a voltage beyond the threshold atmospheric ionization value is applied on a sharp electrode tip mounted at an angle above a microfluidic liquid chamber, the bulk electrohydrodynamic air thrust that is generated results in interfacial shear and, hence, primary azimuthal liquid surface recirculation. This discharge driven vortex mechanism, in turn, causes a secondary bulk meridional liquid recirculation, which produces an inward radial force near the bottom of the chamber. Particles suspended in the liquid are then rapidly convected by the bulk recirculation toward the bottom, where the inward radial force causes them to spiral in a helical swirl-like fashion toward a stagnation point. In particular, we show that these flows, similar to Batchelor flows occurring in a cylindrical liquid column between a stationary and rotating disk, can be used for the separation of red blood cells from blood plasma in a miniaturized device.
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Biomicrofluidics 4, 034104 (2010); http://dx.doi.org/10.1063/1.3474638 (11 pages) | Cited 13 times Online Publication Date: 5 August 2010
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We present an analysis of the results of in situ surface-enhanced Raman scattering (SERS) of bacteria using a microfluidic chip capable of continuously sorting and concentrating bacteria via three-dimensional dielectrophoresis (DEP). Microchannels were made by sandwiching DEP microelectrodes between two glass slides. Avoiding the use of a metal nanoparticle suspension, a roughened metal surface is integrated into the DEP-based microfluidic chip for on-chip SERS detection of bacteria. On the upper surface of the slide, a roughened metal shelter was settled in front of the DEP concentrator to enhance Raman scattering. Similarly, an electrode-patterned bottom layer fabricated on a thin cover-slip was used to reduce fluorescence noise from the glass substrate. Gram positive (Staphylococcus aureus) and Gram negative (Pseudomonas aeruginosa) bacteria were effectively distinguished in the SERS spectral data. Staphylococcus aureus (concentration of 106 CFU/ml) was continuously separated and concentrated via DEP out of a sample of blood cells. At a flow rate of 1 μl/min, the bacteria were highly concentrated at the roughened surface and ready for on-chip SERS analysis within 3 min. The SERS data were successfully amplified by one order of magnitude and analyzed within a few minutes, resulting in the detection of signature peaks of the respective bacteria.
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Pressure-driven transport of particles through a converging-diverging microchannel Biomicrofluidics 3, 022404 (2009); http://dx.doi.org/10.1063/1.3122594 (14 pages) | Cited 12 times Online Publication Date: 22 April 2009
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Pressure-driven transport of particles through a symmetric converging-diverging microchannel is studied by solving a coupled nonlinear system, which is composed of the Navier–Stokes and continuity equations using the arbitrary Lagrangian–Eulerian finite-element technique. The predicted particle translation is in good agreement with existing experimental observations. The effects of pressure gradient, particle size, channel geometry, and a particle’s initial location on the particle transport are investigated. The pressure gradient has no effect on the ratio of the translational velocity of particles through a converging-diverging channel to that in the upstream straight channel. Particles are generally accelerated in the converging region and then decelerated in the diverging region, with the maximum translational velocity at the throat. For particles with diameters close to the width of the channel throat, the usual acceleration process is divided into three stages: Acceleration, deceleration, and reacceleration instead of a monotonic acceleration. Moreover, the maximum translational velocity occurs at the end of the first acceleration stage rather than at the throat. Along the centerline of the microchannel, particles do not rotate, and the closer a particle is located near the channel wall, the higher is its rotational velocity. Analysis of the transport of two particles demonstrates the feasibility of using a converging-diverging microchannel for passive (biological and synthetic) particle separation and ordering.
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Microfluidics as a functional tool for cell mechanics Biomicrofluidics 3, 012006 (2009); http://dx.doi.org/10.1063/1.3067820 (15 pages) | Cited 12 times Online Publication Date: 5 January 2009
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Living cells are a fascinating demonstration of nature’s most intricate and well-coordinated micromechanical objects. They crawl, spread, contract, and relax—thus performing a multitude of complex mechanical functions. Alternatively, they also respond to physical and chemical cues that lead to remodeling of the cytoskeleton. To understand this intricate coupling between mechanical properties, mechanical function and force-induced biochemical signaling requires tools that are capable of both controlling and manipulating the cell microenvironment and measuring the resulting mechanical response. In this review, the power of microfluidics as a functional tool for research in cell mechanics is highlighted. In particular, current literature is discussed to show that microfluidics powered by soft lithographic techniques offers the following capabilities that are of significance for understanding the mechanical behavior of cells: (i) Microfluidics enables the creation of in vitro models of physiological environments in which cell mechanics can be probed. (ii) Microfluidics is an excellent means to deliver physical cues that affect cell mechanics, such as cell shape, fluid flow, substrate topography, and stiffness. (iii) Microfluidics can also expose cells to chemical cues, such as growth factors and drugs, which alter their mechanical behavior. Moreover, these chemical cues can be delivered either at the whole cell or subcellular level. (iv) Microfluidic devices offer the possibility of measuring the intrinsic mechanical properties of cells in a high throughput fashion. (v) Finally, microfluidic methods provide exquisite control over drop size, generation, and manipulation. As a result, droplets are being increasingly used to control the physicochemical environment of cells and as biomimetic analogs of living cells. These powerful attributes of microfluidics should further stimulate novel means of investigating the link between physicochemical cues and the biomechanical response of cells. Insights from such studies will have implications in areas such as drug delivery, medicine, tissue engineering, and biomedical diagnostics.
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Biomicrofluidics 1, 034103 (2007); http://dx.doi.org/10.1063/1.2766761 (10 pages) | Cited 12 times Online Publication Date: 19 July 2007
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We demonstrate here the discovery of a unique and direct three-dimensional biomicrofabrication concept possessing the ability to revolutionize the jet-based fabrication arena. Previous work carried out on similar jet-based approaches have been successful in fabricating only vertical wall/pillar-structures by the controlled deposition of stacked droplets. However, these advanced jet-techniques have not been able to directly fabricate self-supporting arches/links (without molds or reaction methods) between adjacent structures (walls or pillars). Our work reported here gives birth to a unique type of jet determined by high intensity electric fields, which is derived from a specially formulated siloxane sol. The sol studied here has been chosen for its attractive properties (such as an excellent cross-linking nature as well as the ability to polymerize via polycondensation on deposition to its biocompatability), which promotes direct forming of biostructures with nanometer (<50 nm) sized droplets in three dimensions. We foresee that this direct three-dimensional biomicrofabrication jet technique coupled with a variety of formulated sols having focused and enhanced functionality will be explored throughout the physical and life sciences.
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