Actuated Medical Offering Specialized Product Development for MedTech Innovators
Actuated Medical specializes in taking medical devices from concept to market-ready products – from start to finish. They have deep expertise in tissue dynamics and penetration, acoustic engineering, electronics and software development, and 3D printing. They focus exclusively on the development of medical devices and are currently helping other Innovators solve design and regulatory challenges. Actuated’s facility doubled in 2021 and has increased its capacity to conduct contract product development and manufacturing including customer equipment placement.
“Our exceptionally skilled team includes electrical, mechanical, and biomedical engineers with expertise in medical device commercialization. We are currently helping several innovators solve engineering problems. With our expansion, we have the capacity to help others,” said Maureen L. Mulvihill, President and CEO of Actuated Medical.
A recent client is an ER physician. He came to Actuated with a patent for a device and asked Actuated to take his product from concept to FDA submission. Actuated’s engineering team investigated the design and built some feasibility prototypes using Actuated’s rapid prototyping facility. Verification and Validation (V&V) protocols were written, testing was performed, and test reports were completed. Included in V&V was usability testing with 30 participants. The device passed V&V, and Actuated Medical’s team wrote and submitted the 510(k) application. The device is pending FDA clearance.
“I took my patent to Actuated Medical, and they completed all the V&V testing, wrote and submitted the 510(k). Because of Actuated my patent is now a medical device,” said Brian Shippert, DO, Emergency Physician, Shippert Tech, LLC.
Novel accessory designed to facilitate complex endoscopic mucosal resection
Eric M Pauli MD, Joshua S Winder MD, Vamsi V Alli MD
Penn State College of Medicine, Penn State Hershey Medical Center, Hershey, PA.
The GripTract-GI endoscopic tissue manipulator (Figure 1) is a novel cap-based endoscopic accessory designed to facilitate complex endoscopic mucosal resection. The goal of this study is to evaluate the efficacy of the manipulator during en bloc removal of simulated colorectal mucosal lesions in benchtop and preclinical studies.
The primary goals of the platform include; facilitating safe endoscopic submucosal dissection (ESD) methods, broadening application of ESD for clinicians with less extensive training, and improving ESD outcomes. This approach may enable organ sparing surgery in colorectal lesions traditionally deemed endoscopically unresectable. The manipulation of external “fingers” by the clinician using a simple proximal handpiece attached to the endoscope control body enables dynamic traction and countertraction of tissues facilitating electrosurgical knife use during ESD. The technology is compatible with standard colonoscopes and can be attached and removed without altering the colonoscope.
Functional prototypes utilizing this technology were developed and studied as an adjunct in removal of mucosal tissue through ESD. Wet laboratory ESD studies were first performed on porcine stomach tissue by physicians to gain familiarity with the GripTract-GI system and controls. While working with the device, physicians also discovered several unanticipated maneuvers to perform dynamic tissue retraction and to increase the degrees-of-freedom of the electrosurgery tools. These techniques were employed during preclinical porcine studies (n=10 of 14 at time of abstract), where each animal underwent one standard cap-assisted ESD and one GripTract-assisted ESD for comparison. En bloc mucosal resections of up to 6.5 cm2 were performed. Preliminary data shows that with comparable resection areas between standard and GripTract (1.98 ± 0.61 cm2 vs. 2.46 ± 0.80 cm2, p=0.65), resection speeds were also similar (5.33 ± 1.89 mm2/min. standard vs. 5.70 ± 1.55 mm2/min. GripTract, p=0.88). However, the average relative resection speed (GripTract to standard) increased over repeated procedures for each physician, and the perforation rate for GripTract was 50% of that when using standard technique.
In this first preclinical evaluation of the GripTract-GI endoscopic tissue manipulator there was specific utility of this technology to facilitate large mucosal resections. The increase in resection speed with GripTract relative to standard technique over several procedures provides preliminary evidence for a faster learning curve and possible expansion of the pool of clinicians capable of offering ESD – though more studies are warranted before final conclusions are made. Although initially intended for colorectal lesions, this platform has future potential for upper gastrointestinal endoscopy interventions, such as in esophageal or gastric ESD.
Delivery of Low-Intensity Pulsed Ultrasound in the Cortex to Improve Longevity and Performance of Neural Interfaces
NN TIRKO, AS ALSUBHI, JK GREASER, RS CLEMENT, KA SNOOK, RB BAGWELL, ML MULVIHILL
Actuated Medical, Inc., Bellefonte, PA
Chronic neural implants hold great potential for illuminating features of neural function, treating neurological disorders, and enabling the next generation of neuroprosthetics. Penetrating electrode arrays provide direct access to neural signals across the central and peripheral nervous system with high temporospatial resolution. However, a consistent point of failure for chronically implanted microelectrode arrays is poor longevity and variability in functionality of these devices. The foreign body response (FBR) can cause glial scarring and neural cell loss near the electrode sites. The FBR begins with electrode insertion, when damage to the blood brain barrier activates astrocytes and microglia and continues throughout the lifetime of the implant due to the persistent presence of the foreign material in the tissue. Significant efforts have been made to reduce the FBR, both at the outset of implantation by limiting initial insertion damage and over the long-term by reducing the mechanical mismatch between brain and implant, or long-term use of exogenous chemicals to suppress the FBR.
Rather than relying on temporary interventions to limit the FBR, we proposed a method to harness endogenous cortical function to improve the long-term neural interface microenvironment. Low-intensity pulsed ultrasound (LIPUS) has recently been shown to have protective and healing effects in models of cerebral disease and injury, through promotion of brain-derived neurotrophic factor (BDNF) and other neurotrophic factors that affect the anti-inflammatory response of microglia and other cells. Here, we investigate the use of sub-threshold LIPUS focused directly at the neural electrode interface to improve tissue health and increase the quality and longevity of neural recordings. A study was undertaken in which silicon shank electrodes (A4x4-5mm-100-125-703-CM16LP, NeuroNexus, Inc.) oriented at 45º from horizontal, were chronically implanted into cortical layers II/III of the motor or somatosensory cortex of rats (N=8). The effects of LIPUS on neural recording quality over 6 weeks post-implant were studied (n=4) with respect to Sham treatment (n=4). Nominal conditions used were based on the prior LIPUS research on disease and injury; stimulation (0.5 W/cm2 intensity, 1.1 MHz, 15 min. total treatment at 4% duty cycle) was administered daily Week 1, and twice weekly for Weeks 2-6 and coupled with electrophysiology recording sessions (SmartBox Pro Allego, NeuroNexus). Single unit analysis of electrophysiological data reveals strong trends in signal quality improvements in the LIPUS-treated group. More than double the electrode channels remained active throughout the 6 weeks in subjects in the LIPUS stimulation group as compared to Sham (p<0.01). Also, the channels that remained active maintained an average 4 dB higher signal-to-noise ratio (SNR) over the same time period (p<0.01). Our studies demonstrate that periodic application of localized LIPUS to tissue at the neural interface has potential to improve electrophysiology signal quality. Implications for future studies will be discussed.
Microelectrode Arrays Insertion System Using Ultrasonic Vibration to Improve Insertion Mechanics and Reduce Tissue Dimpling and Trauma in the Cortex
NN TIRKO, RS CLEMENT, JK GREASER, AS ALSUBHI, EM STEFFAN, RB BAGWELL, ML MULVIHILL
Actuated Med. Inc., Bellefonte, PA
S LEE, HJ KIM, MF AGHA
University of North Carolina, Chapel Hill, NC
Intracortical Electrode Arrays (IEAs) provide direct access to extracellular neural signals in the brain with high temporal and spatial resolution. Unfortunately, chronically implanted IEAs have limited functional lifespans that impede significant clinical translation. The host tissue reaction is a major contributor to neural interface failure, causing formation of glial scars and loss of neurons at electrode sites. Studies suggest that the initial insertion trauma alone is responsible for significant damage. The forces applied to the cortical tissue during insertion can deform tissue, causing strain and membrane disruptions in underlying neurons and vasculature. While insertion is a technical hurdle common to all IEA types, high-density multi-shank arrays have uniquely significant insertion challenges. Following insertion, the IEA chronic interface can be degraded due to mechanical mismatch between the IEA and the cortical tissue. Superior tissue response and device longevity has been demonstrated with ultra-fine microwire (<15 µm diameter) and flexible (e.g., polyimide) arrays. However, given their tendency to buckle/break during insertion they struggle to penetrate meningeal layers and temporary support structures, shuttles, or dissolvable stiffeners are often necessary for mechanical reinforcement during insertion. This increases the complexity and time of the surgery and insertion process, and may limit reliable electrode performance and adaptation of these arrays.
Ultrasonic vibration of IEAs represents a promising approach to reduce frictional and penetration forces associated with insertion. We have demonstrated that this approach has implantation capability of both rigid, multi-shank arrays and mechanically soft microwire or polymer-based arrays. In the case of rigid arrays (i.e. silicon shanks from NeuroNexus, Blackrock and microwires from MicroProbes, Tucker Davis Technologies) vibration-assisted insertion reduces insertion force 61-82% relative to standard insertion via stereotaxic equipment when using an agar model (0.5% base, 1.5% top layer). In vivo studies demonstrated a significant (p<0.01) reduction in cortical surface dimpling/compression with vibration during insertion of silicon arrays (NeuroNexus H-series) into rat cortex, as well as successful insertion through the dura. Electrodes inserted with vibration have no detriment to electrophysiology signal quality.
In the case of flexible arrays, vibration-assisted insertion both reduces insertion force and improves insertion trajectory. Polyimide thin-film single-shanks probes were inserted in rat nucleus accumbens without vibration (n=6), with vibration through pia (n=10) and with vibration through dura (n=5). Using T2-weighted MRI, insertion accuracy was measured; targeting success was improved with vibration (through pia: 70%, through dura: 83%) as compared to Control (50%; p>0.05 due to limited sample size). Ten days after surgery, neuromodulation outcomes (evoked response patterns, as measured through fMRI) were increased with the vibration-inserted electrodes (through pia: 100%, through dura: 80%) versus Control (66%). Additionally, histological evaluation of the implantation site (4 weeks post-op) revealed that the intensity of glial scaring (visualized via glial fibrillary acidic protein immunohistochemistry) was significantly reduced when electrodes were inserted with vibration (p<0.05) relative to Control. Together, these benchtop insertion studies in agar and ex vivo tissue models, as well as in vivo insertion studies support the potential of vibrated insertion for improved outcomes for studies using IEAs, specifically for flexible electrodes.
Our President and CEO, Maureen L. Mulvihill Awarded the Life Sciences Pennsylvania 2020 CEO of the Year Award
She was honored at the Life Sciences Pennsylvania annual awards ceremony, which was held on May 26, 2021. The award recognizes a CEO who has demonstrated exemplary leadership and active participation to advance the science industry. Maureen did just that throughout the year of 2020, by leading her team at Actuated Medical, Inc., through a trying time, while simultaneously innovating solutions to solve clinical and community needs brought on by the pandemic. Maureen and her team quickly reacted to the Covid-19 pandemic by standing up a reusable face shield manufacturing line in just seven days. The team shipped shields to first responders, manufacturers, schools, and many more.
Frank Baldino, Jr., founder, and CEO of Cephalon, Inc., was a pillar of the Life Sciences community in the Greater Philadelphia region and of the biotechnology industry. Life Sciences Pennsylvania (LSPA) was founded in 1989 by two Penn State researchers and has grown to represent the entire life sciences industry. Their portfolio includes, medical device companies, pharmaceutical companies, investment organizations, research institutions, and myriad service industries. LSPA provides members with one of a kind networking opportunities to help them facilitate strategic connections.
The Life Sciences Pennsylvania Annual Awards Ceremony was held outdoors this year in a “drive-in style event”. Teams came together to celebrate the accomplishments of the Life Sciences industry. It is being held on May 26, 2021, from 3:00 to 5:00 PM. For more information visit: https://lifesciencespa.org/connect/events/2021-annual-awards-program/