Won the Best Paper Award
Abstract : Reduced fluid-structure interaction models have received a considerable attention in recent years being the key component of hemodynamic modeling. A variety of models applying to specific physiological components such as arterial, venous and cerebrospinal fluid (CSF) circulatory systems have been developed based on different approaches. The purpose of this paper is to apply the general approach based on Hamilton’s variational principle to create a model for a viscous Newtonian fluid – structure interaction (FSI) in a compliant bifurcated network. This approach provides the background for a correct formulation of reduced FSI models with an account for arbitrary nonlinear visco-elastic properties of compliant boundaries. The correct boundary conditions are specified at junctions, including matching points in a combined 3D/1D approach. The hyperbolic properties of derived mathematical model are analyzed and used, constructing the monotone finite volume numerical scheme, second-order accuracy in time and space. The computational algorithm is validated by comparison of numerical solutions with the exact manufactured solutions for an isolated compliant segment and a bifurcated structure. The accuracy of applied TVD (total variation diminishing) and Lax-Wendroff methods are analyzed by comparison of numerical results to the available analytical smooth and discontinuous solutions.
Pulse wave velocity (PWV) is an important index of arterial hemodynamics, which lays the foundation for continuous, noninvasive blood pressure automated monitoring. The goal of this paper is to re-examine the accuracy of PWV prediction based on a traditional homogeneous structural model for thin-walled arterial segments. In reality arteries are described as composite heterogeneous hyperelastic structures, where the thickness dimension cannot be considered small compared to the cross section size. In this paper we present a hemodynamic fluid – structure interaction model accounting for the 3D material description of multilayer arterial segments based on its histological information. The model is suitable to account for the highly nonlinear orthotropic material undergoing finite deformation for each layer. An essential ingredient is the notable dependence of results on nonlinear aspects of the model: convective fluid phenomena, hyperelastic constitutive relation for each layer, and finite deformation. The dependence of PWV on pressure for three vessels of different thicknesses is compared against a simplified thin wall model of a membrane shell interacting with an incompressible fluid. Results show an asymptotic accuracy of an order of h/r0 is predicted. This work help lays the foundation for continuous, noninvasive blood pressure automated monitoring based on PWV.
This paper reports an Aerosol-Jet printed micro scale Lead Zirconate Titanate (PZT) energy harvester directly sintered on a low melting point substrate in less than 1 msec using photonic sintering technology. To improve the output signal, d33 piezoelectric mode was employed by patterning silver electrodes as an interdigitated structure on top of a PZT film. The size of the device is 15.5 mm ×13.5 mm ×0.2 mm. Up to 2.4 V was measured at 145 MPa tensile bending stress level in the device after poling at 180 °C for 2 hours with an electric field of 30 kV/cm. Using an oscillating stress (~2.5 Hz) of approximately 145 MPa, the power as a function of load was determined by connecting the device with various series resistive loads. A maximal power of 0.1 μW was generated when driving into a 10 MΩ load. A PZT energy harvester, for the first time, is demonstrated which has been directly printed and sintered on a low melting temperature flexible substrate without a film transfer processes. This not only dramatically simplifies the fabrication process, but expands the possible substrate materials for PZT energy harvesters.
Traumatic brain Injury (TBI) has emerged as the signature injury of modern war, impacting over 300,000 Servicemembers since 2000. While 82% of these injuries are classified mild, there is significant concern with the potential for long-lasting neurocognitive and neuro degenerative effects. Diagnosis of mild TBI is difficult, with symptoms that are wide-ranging, non-specific, and often delayed in onset. The Blast Gauge® System was created to provide an objective measure of blast overpressure and acceleration exposure, providing triage data to assist in identifying soldiers at risk of TBI and detailed waveforms to enable correlation of singular and repetitive exposure to acute and chronic injury. From concept to deployment in 11 months and company formation to first product shipment in 4 months, this MEMS-based soldier-borne blast dosimeter has rapidly provided a new capability to track exposure in training and operations for the US DoD, law enforcement, and international militaries. Widespread deployment of the technology has yielded new insight into previously unrecognized dangers of heavy weapons training and captured valuable information about lED exposures in theater.
Development of ECG delineation algorithms has been an area of intense research in the field of computational cardiology for the past few decades. However, devising evaluation techniques for scoring and/or merging the results of such algorithms, both in the presence or absence of gold standards, still remains as a challenge. This is mainly due to existence of missed or erroneous determination of fiducial points in the results of different annotation algorithms. The discrepancy between different annotators increases when the reference signal includes arrhythmias or significant noise and its morphology deviates from a clean ECG signal. In this work, we propose a new approach to evaluate and compare the results of different annotators under such conditions. Specifically, we use sequence alignment techniques similar to those used in bioinformatics for the alignment of gene sequences. Our approach is based on dynamic programming where adequate mismatch penalties, depending on the type of the fiducial point and the underlying signal, are defined to optimally align the annotation sequences. We also discuss how to extend the algorithm for more than two sequences by using suitable data structures to align multiple annotation sequences with each other. Once the sequences are aligned, different heuristics are devised to evaluate the performance against a gold standard annotation, or to merge the results of multiple annotations when no gold standard exists.
A novel and easily implemented delineation algo- rithm is presented, which allows the foot of the photoplethsymo- gram to be located with sufficient accuracy for heart rate vari- ability applications. This algorithm combines classical delineation techniques with the robustness of the wavelet transform. It can be implemented with a set of FIR filters and simple non-adaptive thresholding, making it suitable for real-time ambulatory appli- cations. Results show that the accuracy of the algorithm matches that of a standard electrocardiogram delineation algorithm, the current standard for heart rate variability applications. The algorithm presented herein is also compared against four state- of-the-art delineation algorithms. Using a database that contains exercise data from thirteen patients across six activity levels and 7012 beats, a temporal accuracy of 3.8±2.6 ms (mean±std) was achieved with a sensitivity of 99.29% and a positive predictive value of 99.23%.
Tactical officers and military personnel who train in explosive entry techniques regularly put themselves at risk of blast exposure. The overpressure conditions in complex military and law enforcement environments, such as interior doors, hallways, and stairwells, cannot be accurately predicted by standard blast models which were developed from outdoor, free-field blasts. In both training and operations, small, low- cost blast overpressure sensors would provide the benefit of tracking exposure levels of at-risk individuals. The sensors would allow, for the first time, direct determination of safe stand-off distances and positioning for personnel during explosive breaching. Overpressure, impulse, and acceleration data has been captured for a series of interior and exterior blasts, demonstrating the utility of the Blast Gauge system as a training and research tool to quantify blast overpressure in complex environments.
An algorithm to automatically locate QRS complexes in noninvasive fetal ECG signals is described and was entered in the PhysioNet/CinC 2013 “Noninvasive Fetal ECG” challenge. The algorithm is based on an iterative subspace decomposition and filtering of the maternal ECG components from the recordings of a set of electrodes placed on the mother’s abdomen. Once the maternal components are removed, a novel merging technique is applied to merge the recordings and generate a signal with a higher SNR to perform fetal peak detection. The algorithm produces an annotation file for each data set containing the location of the fetal QRS complexes in that set. The final results indicate that the algorithm is able to detect fetal peaks under different scenarios and for variety of devices and signals encountered in clinical practice.
Compressed sensing has the possibility to signif- icantly decrease the power consumption of wireless medical devices. The photoplethysmogram (PPG) is a device which can greatly benefit from compressed sensing due to the large amount of power needed to capture data. The aim of this paper is to determine if the least absolute shrinkage and selection operator (LASSO) optimization algorithm is the best approach for reconstructing a compressively sampled PPG across varying physiological states. The results show that LASSO reconstruction approaches but does not surpass, the reliability of constrained optimization.
A MEMS fabrication technique is presented that extends the capabilities of micromachining by combining traditional approaches with direct write dispensing technology. A test device was designed and fabricated to demonstrate the capability of the technique to integrate additional features with three-dimensional direct-write dispensing tools (Optomec, Albuquerque, NM, USA) and (nScrypt, Inc. Orlando, FL, USA). Micro-diaphragms, fabricated using traditional MEMS techniques, are actuated pneumatically via multilayer structures written directly upon the MEMS device.
Due to the very small size of the mouse inner ear, 600 nL volume, developing effective, controlled infusion systems is quite challenging. Key technologies have been created to minimize both size and power for an implantable pump for murine intracochlear infusions. A method for coupling fine capillary tubing to microfluidic channels is presented which provides low volume, biocompatible interconnects withstanding pressures as high as 827 kPa (120 psi) and consuming less than 20 nL of volume exiting in-plane with the pump. Surface micromachined resistive bridges integrated into the flow channel for anemometry based flow rate measurement have been optimized for low power operation in the ultra-low flow rate regime. A process for creation of deformable diaphragms over pump chambers with simultaneous coating of the microfluidic channels has been developed allowing integration of a biocompatible fluid flow path. These advances represent enabling capabilities for a drug delivery system suitable for space constrained applications such as subcutaneous implantation in mice.
The honors program in the Kate Gleason College of Engineering at Rochester Institute of Technology began in 2002. The program admits approximately thirty first year students each year and focuses upon product innovation in a global economy. The goal of the program is to provide talented engineering students with a full appreciation of the product development cycle, from concept to realization; in particular, how products are conceived, how decisions are made at the corporate level to pursue certain products and not others, and how product concepts are refined, engineered, and then manufactured for the marketplace. The first strategy being used is a two academic year course sequence covering topics ranging from teamwork and leadership to globalization. The second strategy involves taking students on two comprehensive “field trips” – one domestic and the other international, where students explore how companies, large and small, address product development. Prior to each trip students present background material on each company and after the company visit students engage in a discussion of the company’s strengths, weaknesses, opportunities and threats. This paper will describe the successful integration of this specialized series of courses with the domestic and international company visits to achieve student appreciation of product development in a global marketplace. Program and course assessment results will be presented.
The design, fabrication, and testing of micro- cannulae with integrated insertion stops is presented. The micro-cannulae were engineered through the use of a silicon micro-mold fabricated via bulk-silicon micro-machining techniques. The use of microelectronic fabrication techniques allows precise control of three critical parameters, insertion depth, interface contact area, and tubing out of round. Worst case variations were found to be 5μm for insertion depth, 502μm2 for interface contact area, and 7% for tip out of round. Histological evaluation revealed the cannula to be located correctly within the basal portion of scala tympani.
Combining several one-dimensional miniaturized separation techniques in series has the potential to be an exceptionally comprehensive analysis approach. Sample species can be separated and identified based on a battery of characteristics not available from any single technique. µIEF is attractive as a first dimension of such a multi-dimensional system due to the equilibrium nature of the final separation, rapid separation capabilities (1min), concentrating qualities (100×), and high resolution (ΔpI = 0.005). As a step towards integration of µIEF with a second dimension (e.g., miniaturized capillary electrophoresis), this work investigates the robustness of µIEF as an initial dimension and explores means to reliably extract a purified, concentrated sample zone from a complete µIEF assay.
This work focuses on capillary isoelectric focusing (cIEF) as a high-resolution sample separation technique applicable for miniaturization and use in portable hand-held analysis systems. Miniaturization of cIEF reduces the amount of time necessary to complete a separation and allows for full-field array detection instead of traditional single-point detection. A miniature cIEF system was employed for rapid cIEF separations of fluorescently-labeled peptides. For enhanced portability, superbright blue LED’s were used as excitation sources and a CCD camera was used for detection. This system offers minimized sample dispersion, a 1nM detection limit, and a separation time of less than I minute.
Sample handling in miniaturized bioanalytical instruments typically depends on pressure or electrokinetic effects. This is particularly true of post-separation detection processes where a sample is moved past a single point detector. In contrast to such methods, the present study investigates a separation system that takes advantage of a steady-state, stationary separation technique known on the macroscale as capillary isoelectric focusing (cIEF). Due to the stationary nature of the final separation, sample analysis is conducted entirely without mobilization. This work explores the merits and limitations associated with miniaturizing this technique. Analyses were conducted on fluorescent peptide and protein samples in miniaturized separation columns (capillaries and glass micromachined channels between 8 and 14 mm long). In the interest of developing overall system portability, blue light emitting diodes (LED’s) were used for sample excitation. Detection was accomplished using a charge-coupled device (CCD). This approach yielded complete multi-sample separations in less than 1 minute.
Application of a full-field detection approach to a biological sample separation scheme known as capillary isoelectric focusing (cIEF) has yielded detailed spatial and temporal information about the transport processes associated with this technique, as well as the efficiency of this separation scheme. The full-field cIEF detection technique utilizes an illumination source such as blue light emitting diodes or a mercury arc lamp, microscope objectives, and a charged coupled device (CCD) camera to image fluorescently labeled proteins and peptides. Interest in this approach arises from the ability to collect, in real time, information from the entire length of the separation channel. This full-field detection eliminates the need for flow mobilization and aids in the empirical analysis of the separation process. In an effort to optimize a miniaturized cIEF system, the full-field detection approach was used as a diagnostic to gauge the effect of varying the channel wall surface charge distribution.
Cell-based biosensors utilize whole cells as the primary transducer to detect a biologically active agent as a cellular signal. A secondary transducer converts this cellular signal into an electrical signal that can be processed and analyzed. Although these sensors have shown success in detecting the presence of biological agents, efforts to classify the type of agent have proven difficult for several reasons. One reason for ambiguities in output signal interpretation is that multiple biochemical pathways can lead to the same cellular response. However, a new approach described in this paper translates this crosstalk noise into common-mode noise that can be rejected. This approach uses a differential measurement between wild-type cells and cells genetically engineered to lack a specific receptor (knockouts). Any biological agent that targets that receptor will evoke a response in the wild-type cell but not in the knockout. This approach provides the benefits of a functional assay with specificity while simplifying signal analysis. This concept was successfully implemented using genetically engineered mouse myocardial cells that lacked the β1-adrenergic receptor (β1-AR).
The use of cell based biosensors outside of the laboratory has been limited due to many issues including preparation of the sample, maintenance of the biological environment, incorporation of the appropriate sensors, and integration of the electronics for data collection and analysis. This paper describes these system issues and briefly presents current efforts to address packaging, fluidics, and data interpretation. These include the development of an integrated silicon-PDMS cell cartridge system that provides reliable electrical and fluidic interconnect and a regulated cell environment, the development of low power and low overhead sensors and electronics, and the necessary fluidic sample preparation.
The use of cell based biosensors for applications outside of the laboratory has been limited in part due to packaging issues. A design for an integrated cell cartridge that addresses the requirements of sterile fluidic interconnect and environmental regulation is presented. The device consists of a PDMS (polydimethylsiloxane) part, a glass cover, and a silicon sensing die mounted on a printed circuit board. The PDMS part forms the fluidic channels, interconnect ports, septa, and two 10 μl chambers over the active sensing area. The silicon die will include integrated biological sensors and a temperature regulation system, and the glass cover seals the chambers. Electrical and fluidic connections are made simultaneously as needles pierce septa on the cartridge when it is plugged into a zero-insertion force (ZIF) socket. The viability of injecting suspended cells into a 10 μl volume chamber and culturing them for greater than one week using a continuous flow perfusion system has been demonstrated. Initial prototypes of the cell cartridges have been assembled and cells have been cultured in the 10 μl PDMS chambers.
The broad-spectrum sensitivity of cell based biosensors offers the capability for detecting previously unknown biological agents. One cellular parameter that is often measured is the action potential of electrically active cells. However, the complexity of this signal makes interpretation of the cellular response to a compound difficult to interpret. By analyzing shifts in the signal’s power spectrum, it may be possible to classify the ionic channels modulated by the agent.
A system is described for the measurement of action potentials from cells cultured on a planar microelectrode array. Experimental results, simulations, and analyses are presented for three pharmaceuticals tested on chick myocardial cells. While the actual agents could readily be distinguished experimentally, the models used for simulation were a partial success, accurately predicting the response to one of the three agents tested.
A new method is presented for microfabricating silicon-based neural probes that are designed for neurobiology research. Such probes provide unique capabilities to record high-resolution signals simultaneously from multiple, precisely defined locations within neural tissue. The fabrication process utilizes a plasma etch to define the probe outline, resulting in sharp tips and compatibility with standard CMOS processes. A low-noise amplifier array has been fabricated through the MOSIS service to complete a system that has been used in multiple successful physiological experiments.
Systems designed to significantly reduce equipment cost and size for neurophysiological studies and hybrid biosensor applications were developed. Custom integrated circuits, each providing eighteen channels of amplification and filtering were designed, fabricated and tested. Planar arrays of iridium microelectrodes were fabricated and packaged in a standard 40 pin dual-in-line package for cultured cell and neural slice preparation studies. An impedance imaging system was developed to monitor the impedance of the cell / electrode interface across the array, thereby expanding the possible biosensor applications to non-electrically active cell types. Thermal regulation was achieved via a Peltier effect thermoelectric device allowing temperature control both above and below ambient temperature. While designed to work together, the system components presented may be easily applied to existing systems for enhancement of capabilities while reducing size and cost.
The impedance characteristics of individual cell / electrode systems are used to monitor cellular viability, position, adhesion, and response to external stimuli in hybrid biosensor applications. A planar microelectrode array consisting of 36 platinized iridium electrodes (10 μm diameter) is used as a substrate for the culture of mammalian cells. Electrode impedance is monitored across the array as different environmental factors are changed. Maps of electrode impedance have been shown to correlate directly to cell positioning over an electrode and general cellular viability. Exposure to a well known voltage-gated Na+ channel blocker (tetrodotoxin) provided significant cellular response as compared to control electrodes without cells. The effective use of small electrodes (10μm diameter) to study single cell / electrode interactions has been demonstrated.
The optical performance of Markle-Dyson projection optics is now well established. Here we describe options for 1X reflective optical masks that might achieve the desired linewidth control. One option is the use of aluminum as the reflecting material. A film less than 50 nm thick has nearly twice the reflectivity of the silicon used until now, and so it should be possible to develop an etching process (for such a thin film) that is adequately precise. Moreover options exist for repairing both opaque and clear defects. An interesting alternative configuration, that eliminates the need to etch the aluminum, is to use a patterned absorber on the substrate and to deposit the aluminum over the patterned absorber.
An all-aluminum MEMS process (Al-MEMS) for the fabrication of large-gap electrostatic actuators is presented. The process is purely additive above the substrate and thereby permits a high degree of design freedom. All process steps are compatible with the future addition of underlying CMOS control circuits. Multilayer aluminum metallization is used with organic sacrificial layers to build up the actuator structures. Oxygen-based dry etching is used to remove the sacrificial layers. While this approach has been previously used by other investigators to fabricate optical modulators and displays, the specific process presented herein has been optimized for driving mechanical actuators with relatively large travels and/or out-of-plane attachments such as electroplated “digits”. The gap height between the actuator and the underlying eletrode(s) can be set using an adjustable polyimide sacrificial layer and aluminum “post” deposition step. Several Al-MEMS electrostatic actuators designed for use as mechanical actuators are presented.