Complex tissue culture matrices, in which types and concentrations of biological stimuli (e.g. growth factors, inhibitors, or small molecules) or matrix structure (e.g. composition, concentration, or stiffness of the matrix) vary over space, would enable a wide range of investigations concerning how these variables affect cell differentiation, migration, and other phenomena. The major challenge in creating layered matrices is maintaining the structural integrity of layer interfaces without diffusion of individual components from each layer1. Current methodologies to achieve this include photopatterning2-3, lithography4, sequential functionalization5, freeze drying6, microfluidics7, or centrifugation8, many of which require sophisticated instrumentation and technical skills. Others rely on sequential attachment of individual layers, which may lead to delamination of layers9. DGMP overcomes these issues by using an inert density modifier such as iodixanol to create layers of varying densities10. Since the density modifier can be mixed with any prepolymer or bioactive molecule, DGMP allows each scaffold layer to be customized. Simply varying the concentration of the density modifier prevents mixing of adjacent layers while they remain aqueous. Subsequent single step polymerization gives rise to a structurally continuous multilayered scaffold, in which each layer has distinct chemical and mechanical properties. The density modifier can be easily removed with sufficient rinsing without perturbation of the individual layers or their components. This technique is therefore well suited for creating hydrogels of various sizes, shapes, and materials. A protocol for fabricating a 2D-polyethylene glycol (PEG) gel, in which alternating layers incorporate RGDS-350, is outlined below. We use PEG because it is biocompatible and inert. RGDS, a cell adhesion peptide11, is used to demonstrate spatial restriction of a biological cue, and the conjugation of a fluorophore (Alexa Fluor 350) enables us to visually distinguish various layers. This procedure can be adapted for other materials (e.g. collagen, hyaluronan, etc.) and can be extended to fabricate 3D gels with some modifications10.
Catheters used for endovascular navigation in interventional procedures lack dexterity at the distal tip. Neurointerventionists, in particular, encounter challenges in up to 25% of aneurysm cases largely due to the inability to steer and navigate the tip of the micro-catheters through tortuous vasculature to access aneurysms. We overcome this problem with sub-millimeter diameter, hydraulically-actuated hyperelastic polymer devices at the distal tip of micro- catheters to enable active steerability. Controlled by hand, the devices offer complete 3D orientation of the tip. Using pressures up to 400 kPa (4 atm) we demonstrate guidewire-free navigation, access, and coil deployment in vivo , offering safety, ease of use, and design flexibility absent in other approaches to endovascular intervention. We demonstrate the ability of our device to navigate through vessels and to deliver embolization coils to the cerebral vessels in a live porcine model. This indicates the potential for microhydraulic soft robotics to solve difficult access and treatment problems in endovascular intervention.
We propose BPClip, a less than $ 1 USD blood pressure monitor that leverages a plastic clip with a spring-loaded mechanism to enable any smartphone with a flash LED and a camera to measure blood pressure. Unlike prior approaches, our system measured systolic, mean, and diastolic blood pressure using oscillometric measurements that avoid cumbersome per-user calibrations and does not require specialized smartphone models with custom sensors.
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Abstract We propose an ultra-low-cost at-home blood pressure monitor that leverages a plastic clip with a spring-loaded mechanism to enable a smartphone with a flash LED and camera to measure blood pressure. Our system, called BPClip, is based on the scientific premise of measuring oscillometry at the fingertip to measure blood pressure. To enable a smartphone to measure the pressure applied to the digital artery, a moveable pinhole projection moves closer to the camera as the user presses down on the clip with increased force. As a user presses on the device with increased force, the spring-loaded mechanism compresses. The size of the pinhole thus encodes the pressure applied to the finger. In conjunction, the brightness fluctuation of the pinhole projection correlates to the arterial pulse amplitude. By capturing the size and brightness of the pinhole projection with the built-in camera, the smartphone can measure a user’s blood pressure with only a low-cost, plastic clip and an app. Unlike prior approaches, this system does not require a blood pressure cuff measurement for a user-specific calibration compared to pulse transit time and pulse wave analysis based blood pressure monitoring solutions. Our solution also does not require specialized smartphone models with custom sensors. Our early feasibility finding demonstrates that in a validation study with N = 29 participants with systolic blood pressures ranging from 88 to 157 mmHg, the BPClip system can achieve a mean absolute error of 8.72 and 5.49 for systolic and diastolic blood pressure, respectively. In an estimated cost projection study, we demonstrate that in small-batch manufacturing of 1000 units, the material cost is an estimated $0.80, suggesting that at full-scale production, our proposed BPClip concept can be produced at very low cost compared to existing cuff-based monitors for at-home blood pressure management.
Catheters used for endovascular navigation in interventional procedures lack dexterity at the distal tip. Neurointerventionists, in particular, encounter challenges in up to 25% of aneurysm cases largely due to the inability to steer and navigate the tip of the microcatheters through tortuous vasculature to access aneurysms. We overcome this problem with submillimeter diameter, hydraulically actuated hyperelastic polymer devices at the distal tip of microcatheters to enable active steerability. Controlled by hand, the devices offer complete 3D orientation of the tip. Using saline as a working fluid, we demonstrate guidewire-free navigation, access, and coil deployment in vivo, offering safety, ease of use, and design flexibility absent in other approaches to endovascular intervention. We demonstrate the ability of our device to navigate through vessels and to deliver embolization coils to the cerebral vessels in a live porcine model. This indicates the potential for microhydraulic soft robotics to solve difficult access and treatment problems in endovascular intervention.
Cells have the amazing ability not only to sense how stiff their surrounding is but also to physically respond to changes in stiffness. Examples of this cellular response include migration following a stiffness gradient [1–3] and differentiation toward different lineages depending on the substrate stiffness [4]. Historically, cell culture in vitro is performed in a Petri dish made of tissue culture plastic, a material that is extremely stiff compared to native tissue stiffness in vivo. Only in recent years has it been shown that the use of tissue culture plastic neglects the significant influence substrate mechanics or elasticity (more commonly referred to as stiffness – albeit incorrectly – in a biological context) can have on cell behavior. This chapter provides information on how to fabricate more in vivo-like materials by carefully controlling substrate stiffness. Before doing so, the terms stiffness and elasticity need to be defined.
Endovascular procedures are limited by an absence of effective actuation methods for navigation and precise device positioning. The existing panoply of passive guidewires and catheters for the treatment of cerebral aneurysms, in particular, leaves neurointerventionists without a treatment option in at least 25% of patients. A key reason is the inability to steer the tip of the microcatheters in vivo. We overcome this problem with sub-millimeter diameter hydraulically-actuated hyperelastic polymer devices connected over a 160 cm length. These provide controlled 3D orientation of acute tip curvatures beyond 180 degrees at pressures of 400kPa that achieves stable coil deployment in vivo. This method uses saline as the working fluid, and forms a closed system from the steerable tip to the hydraulic actuator offering safety, ease of use, and design flexibility absent in approaches that require external actuation.
Disclosures
T. Gopesh: None. J. Wen: None. D. Santiago-Dieppa: None. B. Yan: None. J. Scott-Pannell: None. A. Khalessi: None. A. Norbash: None. J. Friend: None.
