We have developed an apparatus for easy and consistent etching of small tips suitable for use with a scanning tunneling microscope. Its unique features are free access to the etching region and a continuous supply of electrolyte for the production of many tips in succession.
Emerging cell therapies have created new demands for instruments that will increase processing efficiency. Purification of lymphocytes prior to downstream steps of gene transfer currently relies on centrifugal separation, which has drawbacks in output sample purity and process automation. Here, we present an alternative approach to blood cell purification using acoustic forces in plastic microchannels. We provide details regarding the system's ability to purify lymphocytes relative to other blood cell types while maintaining a high overall recovery, testing performance starting from leukapheresis product, buffy coat, and whole blood. Depending on settings, the device achieves for lymphocytes up to 97% purity and up to 68% recovery, and depletes 98% of monocytes while also reducing red cells and platelets. We expect that future scale-up of our system for increased throughput will enable its incorporation in the cell therapy workflow, and that it could ultimately reduce costs and expand access for patients.
Label-free microfluidic-based cell sorters leverage innate differences among cells (e.g., size and stiffness), to separate one cell type from another. This sorting step is crucial for many cell-based applications. Polystyrene-based microparticles (MPs) are the current gold standard for calibrating flow-based cell sorters and analyzers; however, the deformation behavior of these rigid materials is drastically different from that of living cells. Given this discrepancy in stiffness, an alternative calibration particle that better reflects cell elasticity is needed for the optimization of new and existing microfluidic devices. Here, we describe the fabrication of cell-like, mechanically tunable MPs and demonstrate their utility in quantifying differences in inertial displacement within a microfluidic constriction device as a function of particle elastic modulus, for the first time. Monodisperse, fluorescent, cell-like microparticles that replicate the size and modulus of living cells were fabricated from polyacrylamide within a microfluidic droplet generator and characterized via optical and atomic force microscopy. Trajectories of our cell-like MPs were mapped within the constriction device to predict where living cells of similar size/modulus would move. Calibration of the device with our MPs showed that inertial displacement depends on both particle size and modulus, with large/soft MPs migrating further toward the channel centerline than small/stiff MPs. The mapped trajectories also indicated that MP modulus contributed proportionally more to particle displacement than size, for the physiologically relevant ranges tested. The large shift in focusing position quantified here emphasizes the need for physiologically relevant, deformable MPs for calibrating and optimizing microfluidic separation platforms.
A new method is presented for integrating high performance wire-based inductors into thin, planar, chip-scale formats. The method is designed for compatibility with commonly-used rapid prototyping tools, and fabrication can be automated for volume production. The chip-scale inductors are designed for inductances in the 1-10 nH range, self-resonant frequencies above 5 GHz, and quality factors exceeding 75-100. The process can produce a stand-alone chip or can be integrated with existing multi-chip modules and integrated circuits.
Electrode arrays for recording and stimulation in the central nervous system have enabled numerous advances in basic science and therapeutic strategies. In particular, micro-fabricated arrays with precision size and spacing offer the benefit of accessing single neurons and permit mapping of neuronal function. Similar advances are envisioned toward understanding the autonomic nervous system and developing therapies based on its modulation, but appropriate electrode arrays are lacking. Here, we present for the first time, a multi-channel electrode array suitable for penetration of peripheral nerves having diameters as small as 0.1mm, and demonstrate performance in vivo. These arrays have the potential to access multiple discrete nerve fibers in small nerves. We fabricated and characterized five-channel arrays and obtained preliminary recordings of activity when penetrating rat carotid sinus nerve. The electrodes were constructed using hybrid microfabrication processes. The individual electrode shafts are as small as 0.01mm in diameter and at its tip each has a defined site that is addressable via a standard electronic connector. In addition to acute in vivo results, we evaluate the device by electrochemical impedance spectroscopy. Having established the fabrication method, our next steps are to incorporate the arrays into an implantable configuration for chronic studies, and here we further describe concepts for such a device.
Temporal bone implants can be used to electrically stimulate the auditory nerve, to amplify sound, to deliver drugs to the inner ear and potentially for other future applications. The implants require storage space and access to the middle or inner ears. The most acceptable space is the cavity created by a canal wall up mastoidectomy. Detailed knowledge of the available space for implantation and pathways to access the middle and inner ears is necessary for the design of implants and successful implantation. Based on temporal bone CT scans a method for three-dimensional reconstruction of a virtual canal wall up mastoidectomy space is described. Using Amira® software the area to be removed during such surgery is marked on axial CT slices, and a three-dimensional model of that space is created. The average volume of 31 reconstructed models is 12.6 cm<sup>3</sup> with standard deviation of 3.69 cm<sup>3</sup>, ranging from 7.97 to 23.25 cm<sup>3</sup>. Critical distances were measured directly from the model and their averages were calculated: height 3.69 cm, depth 2.43 cm, length above the external auditory canal (EAC) 4.45 cm and length posterior to EAC 3.16 cm. These linear measurements did not correlate well with volume measurements. The shape of the models was variable to a significant extent making the prediction of successful implantation for a given design based on linear and volumetric measurement unreliable. Hence, to assure successful implantation, preoperative assessment should include a virtual fitting of an implant into the intended storage space. The above-mentioned three-dimensional models were exported from Amira to a Solidworks application where virtual fitting was performed. Our results are compared to other temporal bone implant virtual fitting studies. Virtual fitting has been suggested for other human applications.
We have previously described 2D arrays of several thousand elements operating up to 5.0 MHz for transthoracic cardiac imaging. Lately, there has been interest in developing catheter based intracardiac imaging systems to aid in the precise tracking of anatomical features for improved diagnoses and therapies. We have constructed several arrays for real time intracardiac volumetric imaging based upon two different designs; a 10 X 10 equals 100 element 5.0 MHz forward looking 2D array, and a 13 X 11 equals 143 element 5.0 MHz 2D array for side scanning applications.
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