Space-resolved stimulation of active hydrogel layers can be achieved for example by using a micro-heater array. In the current work, we present the interaction of (i) such a rigid array of heating elements that can be selectively activated and (ii) an active thermo-responsive hydrogel layer that responds to the local stimulus change. Due to the respective local actuation, (iii) the surface form of a passive top-layer can be manipulated. We present continuum-based simulative predictions based on the Temperature Expansion Model and compare them to experimental outcomes for the system.
We establish performance characteristics of needle-type waveguides in three-dimensional array architectures as light delivery interfaces into deep tissue for applications, such as optogenetic and infrared (IR) neural stimulation. A single optrode waveguide achieves as high as 90% transmission efficiency, even at tissue depths >1 mm . Throughout the visible and near-IR spectrum, the effective light attenuation through the waveguide is ∼3 orders of magnitude smaller than attenuation in tissue/water, as confirmed by both simulation and experimental results. Light emission profiles from the optrode tips into tissue were also measured. Beam widths of 70 to 150 μm and full-angle divergence ranging from 13 to 40 deg in tissue can be achieved. These beam characteristics satisfy a wide range of requirements for targeted illumination in neural stimulation.
Penetrating waveguide arrays made of glass (SiOO) and silicon were fabricated for infared (IR) neural stimulation to provide 3D access to the brain or peripheral nerves for selective deep-tissue stimulation with different spatiotemporal patterns. Comprehensive bench characterization was performed to determine light delivery and loss mechanisms. Fused silica/quartz arrays have optrodes of constant geometry with a pyramidal tip at the end of a straight-edge shank; length, width, and tip angle of each optrode can be varied independently from array to array. Undoped silicon arrays are similar in form to the Utah Slant Electrode Array, which has tapered microneedles of varying length in one direction. Light transmission efficiency was investigated with input from different optical fibers. With a 120-μmm wide and 1.5-mm long glass optrode having a tip taper angle of 45° with respect to the optical axis, 70% of IR light from a butt-coupled 50-μm fiber is transmitted out of the tips; shank length and tip taper does not affect the output power. However, transmission is only 39% for a 1.5- mm long Si optrode, and less for shorter more tapered optrodes. Similar beam profiles were obtained for both arrays when glass optrodes have a 45° tip taper; decreasing the glass optrode tip angle to 30° increases the full-angle divergence from 15° to 55°, which leads to a wider yet shallower illumination volume. Results reveal that the dominant source of loss in both devices is from total internal reflection within the tips. Additional losses in silicon include tapered shank radiation and reflection from its high refractive index.
Early-generation penetrating waveguide arrays made of glass (SiO2) were micromachined for optogenetic stimulation in able to provide comprehensive and selective access to distributed targets in three dimensions. We characterized light delivery of the device in order to facilitate design optimization and understand its application in tissue. The glass optrodes were formed by dicing, etching, and annealing. A fused silica/quartz substrate was used to produce 10×10 arrays of optrodes with constant geometry having a pyramidal tip at the end of a straight-edge shank; length, width, spacing, tip angle, and even array size can be varied indepedently. Visible light transmission effciency of optrodes was investigated with input from an optical fiber as well as microscope objective lenses. With a 120-µm wide and 1.5-mm long optrode having a tip taper angle of 30º with respect to the optical axis, almost 90% of visible and IR light from a butt-coupled 50-µm multimode fiber is transmitted out of the optrode tips when optrode shanks are surrounded by tissue. In air, the normalized output power decreases according to the area mismatch betweeen optrode shank and the focused beam width from the microscope; visible light transmission is as much as 90% as well.
Here we present the first use of intraneural and intrafascicular infrared neural stimulation (INS) with early-generation
Utah Slanted Optrode Arrays (USOAs) to produce highly selective, artifact-free stimulation of peripheral nerves.
USOAs utilize technology previously developed for Utah Slanted Electrode Arrays, and contain 100 silicon optrodes of
0.5 to 1.5 mm length, spaced 400 μm apart in a 10 x 10 grid. The optrodes penetrate into the nerve and closely abut
nerve fibers, thus providing multiple, independent, focal sites of stimulation. We first demonstrated that intraneural (but
extrafascicular) infrared (IR) stimulation of cat sciatic nerve with conventional optical fibers coupled to a Lockheed
Martin Aculight Capella laser produced stronger and more selective neural and muscle compound action potentials
(CAPs) than did extraneural INS. We next tested INS through individual USOA optrodes (e.g., wavelength 1873 nm, 5-
ms stimulus pulse, < 1 mJ at optrode tip). In contrast to extraneural INS, intrafascicular INS evoked relatively strong and
highly selective, optrode-specific responses. Further, there were no observable stimulus artifacts, thereby allowing
adjacent electrical recordings. These initial results indicate that intrafascicular INS via USOAs may provide a more
efficient, more selective, high-optrode-count means of activating axons, plus greater access to interior nerve fibers.
We present an early-generation Utah Slant Optrode Array (USOA) for infrared (IR) neural stimulation. Intrafascicular
IR stimulation with the early prototype in the cat sciatic nerve produced highly selective and artifact-free
responses, which outperformed extraneural IR stimulation. We characterized the light delivery and loss mechanisms
of the device in order to facilitate design optimization. Fabrication of the USOA takes advantage of the
extensive research in the development of the Utah Slant Electrode Array (USEA). An undoped (ρ > 20 ω ρ cm)
c-Si (100) substrate was used to produce a 10 x 10 array of optrodes with lengths from 0.5 mm to 1.5 mm in a
400-μm pitch. This substrate is able to transmit IR (λ > 1.1μm) with negligible absorption losses. The optrodes
were coupled to the laser source via fibers of different core diameters through in-coupling interfaces of varying
refractive indices. The effect of these factors on optrode transmission efficiency was investigated. At 1550nm,
transmittance for a butt-coupled 50-μm multimode fiber through a medium of index n = 1.66 was measured as
34.7%, which was the maximum value obtained. When the refractive index of the intervening medium was lowered,
transmission decreased according to Fresnel reflection theory. Above 100-μm core size, transmitted power
decreases by 40% with each doubling of the fiber core diameter. Transmission was also found to be dependent on
the optrode length, where shorter and more tapered optrodes provided less output power. The results suggest
that Fresnel, coupling, and radiation losses are the primary loss mechanisms.
With the rapid development of micro systems technology and microelectronics, smart electronic systems are emerging
for the continuous surveillance of relevant parameters in the body and even for closed-loop systems with a sensor
feedback to drug release systems. With respect to diabetes management, there is a critical societal need for a sensor that
can be used to continuously measure a patient's blood glucose concentration twenty four hours a day on a long-term
basis. In this work, thin films of "stimuli-responsive" or "smart" hydrogels were combined with microfabricated
piezoresistive pressure transducers to obtain "chemomechanical sensors" that can serve as selective and versatile
wireless biomedical sensors. The sensitivity of hydrogels with regard to the concentration of glucose in solutions with
physiological pH, ionic strength and temperature was investigated in vitro. The response of the glucose-sensitive
hydrogel was studied at different regimes of the glucose concentration change and at different temperatures. Sensor
response time and accuracy with which a sensor can track gradual changes in glucose was estimated.
This work is motivated by a demand for inexpensive, robust and reliable biochemical sensors with high signal
reproducibility and long-term-stable sensitivity, especially for medical applications. Micro-fabricated sensors can
provide continuous monitoring and on-line control of analyte concentrations in ambient aqueous solutions. The
piezoresistive biochemical sensor containing a special biocompatible polymer (hydrogel) with a sharp volume phase
transition in the neutral physiological pH range near 7.4 can detect a specific analyte, for example glucose. Thereby the
hydrogel-based biochemical sensors are useful for the diagnosis and monitoring of diabetes. The response of the glucosesensitive
hydrogel was studied at different regimes of the glucose concentration change and of the solution supply.
Sensor response time and accuracy with which a sensor can track gradual changes in glucose was estimated.
Additionally, the influence of various recommended sterilization methods on the gel swelling properties and on the
mechano-electrical transducer of the pH-sensors has been evaluated in order to choose the most optimal sterilization
method for the implantable sensors. It has been shown that there is no negative effect of gamma irradiation with a dose
of 25.7 kGy on the hydrogel sensitivity. In order to achieve an optimum between sensor signal amplitude and sensor
response time, corresponding calibration and measurement procedures have been proposed and evaluated for the
chemical sensors.
Environmentally responsive or smart hydrogels show a volume phase transition due to changes of external stimuli such
as pH or ionic strength of an ambient solution. Thus, they are able to convert reversibly chemical energy into mechanical
energy and therefore they are suitable as sensitive material to be integrated in biochemical microsensors and MEMS
devices. In this work, micro fabricated silicon pressure sensor chips with integrated piezoresistors were used as
transducers for the conversion of mechanical work into an appropriate electrical output signal due to the deflection of a
thin silicon bending plate. Within this work two different sensor designs have been studied. The biocompatible
poly(hydroxypropyl methacrylate-N,N-dimethylaminoethyl methacrylate-tetra-ethyleneglycol dimethacrylate) (HPMADMA-
TEGDMA) was used as an environmental-sensitive element in piezoresistive biochemical sensors. This
polyelectrolytic hydrogel shows a very sharp volume phase transition at pH values below about 7.4 which is in the range
of the physiological pH. The sensor's characteristic response was measured in-vitro for changes in pH of PBS buffer
solution at fixed ionic strength. The experimental data was applied to the Hill equation and the sensor sensitivity as a
function of pH was calculated out of it. The time-dependent sensor response was measured for small changes in pH,
whereas different time constants have been observed. The same sensor principal was used for sensing the ionic strength.
The time-dependent electrical output signal of both sensors was measured for variations in ionic strength at fixed pH
value using PBS buffer solution. Both sensor types showed an asymmetric swelling behavior between the swelling and
the deswelling cycle as well as different time constants, which was attributed to the different nature of mechanical
hydrogel confinement inside the sensor.
The advent of micro and nanotechnologies along with integrated circuit technologies has led to many exciting solutions
in medical field. One of the major applications of microsystems is microelectrodes interfacing neurons for large scale in
vivo sensing, deep brain stimulation and recording. For biomedical microsystems, material selection is a challenge
because biocompatibility has to be considered for implantable electronic devices. We are using flip chip bonding to
integrate a signal processing IC to the Utah electrode array (UEA). Conventionally the flip chip process is used to bond a
die to a substrate or interposer. In this work the electrical interconnects are made from the under bump metallization
(UBM) on the UEA to the solder bumps on the IC. The UBM selection and reliability is one of the critical issues in the
total reliability of a flip chip bumping and interconnection technology. The UBM was optimized to achieve improved
interconnect strength, and its reliability was evaluated by conducting solder ball shear strength testing. The UBM
reliability was tested with two solder metallurgies including AuSn and SnCu0.7. These solders are needed to allow two
reflow processes to be used, an initial higher temperature (350 °C) and a second lower temperature process (250 °C).
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