Bryan C. Petzold

SU-8 force sensing pillar arrays for biological measurements

The generation and sensation of mechanical force plays a role in many dynamic biological processes, including touch sensation. This paper presents a two-axis micro strain gauge force sensor constructed from multiple layers of SU-8 and metal on quartz substrates. The sensor was designed to meet requirements for measuring tactile sensitivity and interaction forces exerted during locomotion by small organisms such as the nematode Caenorhabditis elegans. The device is transparent and compatible with light microscopes, allowing behavioral experiments to be combined with quantitative force measurements. For the first time, we have characterized the scale of interaction forces generated in wild-type C. elegans in probing and responding to their environment during locomotion. The device features sub-microN force resolution from 1 Hz to 1 kHz, >25 microN range, kHz acquisition rates and biocompatibility.

Aluminum nitride on titanium for CMOS compatible piezoelectric transducers.

Piezoelectric materials are widely used for microscale sensors and actuators but can pose material compatibility challenges. This paper reports a post-CMOS compatible fabrication process for piezoelectric sensors and actuators on silicon using only standard CMOS metals. The piezoelectric properties of aluminum nitride (AlN) deposited on titanium (Ti) by reactive sputtering are characterized and microcantilever actuators are demonstrated. The film texture of the polycrystalline Ti and AlN films is improved by removing the native oxide from the silicon substrate in situ and sequentially depositing the films under vacuum to provide a uniform growth surface. The piezoelectric properties for several AlN film thicknesses are measured using laser doppler vibrometry on unpatterned wafers and released cantilever beams. The film structure and properties are shown to vary with thickness, with values of d(33f), d(31) and d(33) of up to 2.9, -1.9 and 6.5 pm V(-1), respectively. These values are comparable with AlN deposited on a Pt metal electrode, but with the benefit of a fabrication process that uses only standard CMOS metals.

Microsystems for biomimetic stimulation of cardiac cells.

The heart is a complex integrated system that leverages mechanoelectrical signals to synchronize cardiomyocyte contraction and push blood throughout the body. The correct magnitude, timing, and distribution of these signals is critical for proper functioning of the heart; aberrant signals can lead to acute incidents, long-term pathologies, and even death. Due to the hearts limited regenerative capacity and the wide variety of pathologies, heart disease is often studied in vitro. However, it is difficult to accurately replicate the cardiac environment outside of the body. Studying the biophysiology of the heart in vitro typically consists of studying single cells in a tightly controlled static environment or whole tissues in a complex dynamic environment. Micro-electromechanical systems (MEMS) allow us to bridge these two extremes by providing increasing complexity for cell culture without having to use a whole tissue. Here, we carefully describe the electromechanical environment of the heart and discuss MEMS specifically designed to replicate these stimulation modes. Strengths, limitations and future directions of various designs are discussed for a variety of applications.

MEMS-based force-clamp analysis of the role of body stiffness in C. elegans touch sensation

Touch is enabled by mechanoreceptor neurons in the skin and plays an essential role in our everyday lives, but is among the least understood of our five basic senses. Force applied to the skin deforms these neurons and activates ion channels within them. Despite the importance of the mechanics of the skin in determining mechanoreceptor neuron deformation and ultimately touch sensation, the role of mechanics in touch sensitivity is poorly understood. Here, we use the model organism Caenorhabditis elegans to directly test the hypothesis that body mechanics modulate touch sensitivity. We demonstrate a microelectromechanical system (MEMS)-based force clamp that can apply calibrated forces to freely crawling C. elegans worms and measure touch-evoked avoidance responses. This approach reveals that wild-type animals sense forces <1 μN and indentation depths <1 μm. We use both genetic manipulation of the skin and optogenetic modulation of body wall muscles to alter body mechanics. We find that small changes in body stiffness dramatically affect force sensitivity, while having only modest effects on indentation sensitivity. We investigate the theoretical body deformation predicted under applied force and conclude that local mechanical loads induce inward bending deformation of the skin to drive touch sensation in C. elegans.

Tissue mechanics govern the rapidly adapting and symmetrical response to touch

Significance Recordings from Pacinian corpuscles in the 1960s showed that touch elicits symmetric activation followed by rapid adaptation. Sinusoidal stimulation resulted in frequency doubling within a sensitive frequency band, suggesting that these receptors function as frequency-tuned vibration sensors. At the time, the surrounding lamellar capsule was proposed to generate these response dynamics by acting as a mechanical filter. However, similar response dynamics have since been seen in many other mechanoreceptors, leading to controversy over the specificity of this hypothesis. Using a combination of in vivo electrophysiology, feedback-controlled mechanical stimulation, and simulation, we resolve this controversy in favor of a systems-level mechanical filter that is independent of specific anatomical features or specific mechanoelectrical transduction channels. Interactions with the physical world are deeply rooted in our sense of touch and depend on ensembles of somatosensory neurons that invade and innervate the skin. Somatosensory neurons convert the mechanical energy delivered in each touch into excitatory membrane currents carried by mechanoelectrical transduction (MeT) channels. Pacinian corpuscles in mammals and touch receptor neurons (TRNs) in Caenorhabditis elegans nematodes are embedded in distinctive specialized accessory structures, have low thresholds for activation, and adapt rapidly to the application and removal of mechanical loads. Recently, many of the protein partners that form native MeT channels in these and other somatosensory neurons have been identified. However, the biophysical mechanism of symmetric responses to the onset and offset of mechanical stimulation has eluded understanding for decades. Moreover, it is not known whether applied force or the resulting indentation activate MeT channels. Here, we introduce a system for simultaneously recording membrane current, applied force, and the resulting indentation in living C. elegans (Feedback-controlled Application of mechanical Loads Combined with in vivo Neurophysiology, FALCON) and use it, together with modeling, to study these questions. We show that current amplitude increases with indentation, not force, and that fast stimuli evoke larger currents than slower stimuli producing the same or smaller indentation. A model linking body indentation to MeT channel activation through an embedded viscoelastic element reproduces the experimental findings, predicts that the TRNs function as a band-pass mechanical filter, and provides a general mechanism for symmetrical and rapidly adapting MeT channel activation relevant to somatosensory neurons across phyla and submodalities.

Piezoresistive Cantilever-based Force-Clamp System for the Study of Mechanotransduction in C. Elegans

Understanding how the mechanoreceptor neurons of Caenorhabditis elegans mediate mechanotransduction can unravel how touch works, but new tools are required to quantitatively analyze the relationship between mechanical loading and the physiological response. Here we present a piezoresistive cantilever-based force clamp system that can apply user-defined force profiles to C. elegans. We present a novel MEMS force-clamp system and demonstrate a piezoresistive cantilever with low 1/f noise, low noise floor and high force resolution suitable for these measurements. Initial studies enabled by the system are also discussed.

High frequency force sensing with piezoresistive cantilevers

We present the design, fabrication and characterization of sub-micron piezoresistive silicon cantilevers for high frequency force detection. The cantilevers are fabricated by a simple three-mask process and doped using POCl3 diffusion, which enables high doping levels and negligible lattice damage. Devices have a force resolution of 298 pN from 1 Hz – 50 kHz (f0=187 kHz) and 678 pN up to 100 kHz (f0=419 kHz), the highest combination of force resolution and measurement bandwidth to date.

A high d 33 CMOS compatible process for aluminum nitride on titanium

We present a CMOS compatible fabrication process which utilizes aluminum nitride with titanium electrodes for high-speed piezoelectric actuation. Aluminum nitride film morphology was improved by maintaining vacuum between film depositions and by the inclusion of an aluminum nitride interlayer. A rocking curve full-width at half-maximum of less than 3 degrees was achieved. Unimorph actuators were fabricated from silicon cantilevers and piezoelectric coefficients of 3.0 pm/V and 1.65 pm/V were measured for d33 and d31, respectively. This performance is comparable to reports for AlN processed without CMOS compatible electrode materials.

Piezoresistive Cantilever Optimization and Applications

Piezoresistors are commonly used in microsystems for transducing force, displacement, pressure and acceleration. Silicon piezoresistors can be fabricated using ion implantation, diffusion or epitaxy and are widely used for their low cost and electronic readout. However, the design of piezoresistive cantilevers is complicated by coupling between design parameters as well as fabrication and application constraints. Here we discuss analytical models and design optimization for piezoresistive cantilevers, and describe several applications ranging from studying electron movement using scanning gate microscopy to measuring the biomechanics of whole organisms.

Exploring Cellular Tensegrity: Physical Modeling and Computational Simulation

The term tensegrity was first coined by Buckminster Fuller to describe a structure in which continuous tension in its members forms the basis for structural integrity. Fuller most famously demonstrated the concept of tensegrity in architecture through the design of geodesic domes while his student, artist Kenneth Snelson, applied the concept of tensegrity to create sculptures that appear to defy gravity (Figure 1). Snelson’s tensegrity sculptures have minimal components and achieve their stability through dynamic distribution of tensile and compressive forces amongst their members to create internal balance [1]. It was upon viewing Snelson’s sculptures that Donald Ingber became inspired by their structural efficiency and dynamic force balance to adopt tensegrity as a paradigm upon which to analyze cell structure and mechanics. It has been 30 years since the premier appearance of the cellular tensegrity model and although the model is still much under debate, empirical evidence suggests that the model may explain a wide variety of phenomena ranging from tumor growth to cell motility [1–4].Copyright