Biomedical Microdevices 

About: Biomedical Microdevices is an academic journal published by Springer Science+Business Media. The journal publishes majorly in the area(s): Microfluidics & Medicine. It has an ISSN identifier of 1387-2176. Over the lifetime, 1888 publications have been published receiving 67134 citations.

Characterization of polydimethylsiloxane (PDMS) properties for biomedical micro/nanosystems.

Abstract: Polydimethylsiloxane (PDMS Sylgard® 184, Dow Corning Corporation) pre-polymer was combined with increasing amounts of cross-linker (5.7, 10.0, 14.3, 21.4, and 42.9 wt.%) and designated PDMS1, PDMS2, PDMS3, PDMS4, and PDMS5, respectively. These materials were processed by spin coating and subjected to common microfabrication, micromachining, and biomedical processes: chemical immersion, oxygen plasma treatment, sterilization, and exposure to tissue culture media. The PDMS formulations were analyzed by gravimetry, goniometry, tensile testing, nanoindentation, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Spin coating of PDMS was formulation dependent with film thickness ranging from 308 μm on PDMS1 to 171 μm on PDMS5 at 200 revolutions per minute (rpm). Ultimate tensile stress (UTS) increased from 3.9 MPa (PDMS1) to 10.8 MPa (PDMS3), and then decreased down to 4.0 MPa (PDMS5). Autoclave sterilization (AS) increased the storage modulus (σ) and UTS in all formulations, with the highest increase in UTS exhibited by PDMS5 (218%). PDMS surface hydrophilicity and micro-textures were generally unaffected when exposed to the different chemicals, except for micro-texture changes after immersion in potassium hydroxide and buffered hydrofluoric, nitric, sulfuric, and hydrofluoric acids; and minimal changes in contact angle after immersion in hexane, hydrochloric acid, photoresist developer, and toluene. Oxygen plasma treatment decreased the contact angle of PDMS2 from 109∘ to 60∘. Exposure to tissue culture media resulted in increased PDMS surface element concentrations of nitrogen and oxygen.

Three-Dimensional Photopatterning of Hydrogels Containing Living Cells

Abstract: Recent advances in tissue engineering have leveraged progress in both polymer chemistry and cell biology. For example, photopolymerizable biomaterials have been developed that can be used to photoencapsulate cells in peptide-derivatized hydrogel networks. While these materials have been useful in bone, cartilage and vascular tissue engineering, they have limited applicability to more complex tissues that are characterized by precise cell and tissue organization (e.g., liver, kidney). Typically, the tissue shape has been defined solely by the container used for photopolymerization. In this paper, we describe the use of photolithographic techniques to broaden the capability of photopolymerizable PEG-based biomaterials by inclusion of structural features within the cell/hydrogel network. Specifically, we describe the development of a photopatterning technique that allows localized photoencapsulation of live mammalian cells to control the tissue architecture. In this study, we optimized the effect of ultraviolet (UV) exposure and photoinitiator concentration on both photopatterning resolution and cell viability. With regard to photopatterning resolution, we found that increased UV exposure broadens feature size, while photoinitiator concentration had no significant effect on patterning resolution. Cell viability was characterized using HepG2 cells, a human hepatoma cell line. We observed that UV exposure itself did not cause cell death over the doses and time scale studied, while the photoinitiator 2,2-dimethoxy-2-phenyl-acetophenone was itself cytotoxic in a dose-dependent manner. Furthermore, the combination of UV and photoinitiator was the least biocompatible condition presumably due to formation of toxic free radicals. The utility of this method was demonstrated by photopatterning hydrogels containing live cells in various single layer structures, patterns of multiple cellular domains in a single “hybrid” hydrogel layer, and patterns of multiple cell types in multiple layers simulating use in a tissue engineering application. The combination of microfabrication approaches with photopolymerizable biomaterials will have implications in tissue engineering, elucidating fundamental structure–function relationships of tissues, and formation of immobilized cell arrays for biotechnological applications.

3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood

Abstract: Detection of circulating tumor cells has emerged as a promising minimally invasive diagnostic and prognostic tool for patients with metastatic cancers. We report a novel three dimensional microfilter device that can enrich viable circulating tumor cells from blood. This device consists of two layers of parylene membrane with pores and gap precisely defined with photolithography. The positions of the pores are shifted between the top and bottom membranes. The bottom membrane supports captured cells and minimize the stress concentration on cell membrane and sustain cell viability during filtration. Viable cell capture on device was investigated with scanning electron microscopy, confocal microscopy, and immunofluorescent staining using model systems of cultured tumor cells spiked in blood or saline. The paper presents and validates this new 3D microfiltration concept for circulation tumor cell enrichment application. The device provides a highly valuable tool for assessing and characterizing viable enriched circulating tumor cells in both research and clinical settings.

BBB ON CHIP: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function

Abstract: The blood-brain barrier (BBB) is a unique feature of the human body, preserving brain homeostasis and preventing toxic substances to enter the brain. However, in various neurodegenerative diseases, the function of the BBB is disturbed. Mechanisms of the breakdown of the BBB are incompletely understood and therefore a realistic model of the BBB is essential. We present here the smallest model of the BBB yet, using a microfluidic chip, and the immortalized human brain endothelial cell line hCMEC/D3. Barrier function is modulated both mechanically, by exposure to fluid shear stress, and biochemically, by stimulation with tumor necrosis factor alpha (TNF-α), in one single device. The device has integrated electrodes to analyze barrier tightness by measuring the transendothelial electrical resistance (TEER). We demonstrate that hCMEC/D3 cells could be cultured in the microfluidic device up to 7 days, and that these cultures showed comparable TEER values with the well-established Transwell assay, with an average (± SEM) of 36.9 Ω.cm2 (± 0.9 Ω.cm2) and 28.2 Ω.cm2 (± 1.3 Ω.cm2) respectively. Moreover, hCMEC/D3 cells on chip expressed the tight junction protein Zonula Occludens-1 (ZO-1) at day 4. Furthermore, shear stress positively influenced barrier tightness and increased TEER values with a factor 3, up to 120 Ω.cm2. Subsequent addition of TNF-α decreased the TEER with a factor of 10, down to 12 Ω.cm2. This realistic microfluidic platform of the BBB is very well suited to study barrier function in detail and evaluate drug passage to finally gain more insight into the treatment of neurodegenerative diseases.

Combined microfluidic-micromagnetic separation of living cells in continuous flow.

Abstract: This paper describes a miniaturized, integrated, microfluidic device that can pull molecules and living cells bound to magnetic particles from one laminar flow path to another by applying a local magnetic field gradient, and thus selectively remove them from flowing biological fluids without any wash steps. To accomplish this, a microfabricated high-gradient magnetic field concentrator (HGMC) was integrated at one side of a microfluidic channel with two inlets and outlets. When magnetic micro- or nano-particles were introduced into one flow path, they remained limited to that flow stream. In contrast, when the HGMC was magnetized, the magnetic beads were efficiently pulled from the initial flow path into the collection stream, thereby cleansing the original fluid. Using this microdevice, living E. coli bacteria bound to magnetic nanoparticles were efficiently removed from flowing solutions containing densities of red blood cells similar to that found in blood. Because this microdevice allows large numbers of beads and cells to be sorted simultaneously, has no capacity limit, and does not lose separation efficiency as particles are removed, it may be especially useful for separations from blood or other clinical samples. This on-chip HGMC-microfluidic separator technology may potentially allow cell separations to be carried out in the field outside of hospitals and clinical laboratories.