Publications

The delivery of macromolecular drugs via the gastrointestinal (GI) tract is challenging as these drugs display low stability as well as poor absorption across the intestinal epithelium. While permeation-enhancing drug delivery methods can increase the bioavailability of low molecular weight drugs, the effective delivery of high molecular weight drugs across the tight epithelial cell junctions remains a formidable challenge. Here, we describe autonomous microinjectors that are deployed in the GI tract, then efficiently penetrate the GI mucosa to deliver a macromolecular drug, insulin, to the systemic circulation. We performed in vitro studies to characterize insulin release and assess the penetration capability of microinjectors and we measured the in vivo release of insulin in live rats. We found that the microinjectors administered within the luminal GI tract could deliver insulin transmucosally to the systemic circulation at levels similar to those with intravenously administered insulin. Due to their small size, tunability in sizing and dosing, wafer-scale fabrication, and parallel, autonomous operation, we anticipate that these microinjectors will significantly advance drug delivery across the GI tract mucosa to the systemic circulation in a safe manner.

In this paper, we have used helical nanomachines to measure the local rheological properties of a viscoelastic media. The position of the helical nanomachine/nanopropeller was controlled precisely using magnetic fields with simultaneous measurements of the mechanical properties of a complex and heterogeneous fluidic environment. We demonstrated that the motion of the helical nanopropeller is extremely sensitive to fluid elasticity and the speed of propulsion of the nanopropeller can be used as a measure of the local elastic relaxation time.

Extended-release gastrointestinal (GI) luminal delivery substantially increases the ease of administration of drugs and consequently the adherence to therapeutic regimens. However, because of clearance by intrinsic GI motility, device gastroretention and extended drug release over a prolonged duration are very challenging. Here, we report that GI parasite–inspired active mechanochemical therapeutic grippers, or theragrippers, can reside within the GI tract of live animals for 24 hours by autonomously latching onto the mucosal tissue. We also observe a notable sixfold increase in the elimination half-life using theragripper-mediated delivery of a model analgesic ketorolac tromethamine. These results provide first-in-class evidence that shape-changing and self-latching microdevices enhance the efficacy of extended drug delivery.

In this communication, the magnetic dipole moment of untethered thermally responsive sub mm scale grippers is optimized for efficient coupling to external magnetic resonance (MR) fields. Gripper encapsulation in a millimeter sized wax pellet reduces the friction with the surrounding tissue and magnetic resonance navigation (MRN) of a sub mm scale microgripper is realized within narrow channels in tissue phantoms and in an ex vivo porcine esophagus. The results show convincing proof-of-concept evidence that it is possible to sequentially, image, move and guide a sub-millimeter functional microsurgical tool in tissue conduits using a commercial preclinical MR system, and is an important step towards the clinical translation of untethered microtools.

A new class of microswimmers are presented which are capable of reversing their direction of swimming without requiring a reversal in direction of field rotation. These swimmers exploit heterogeneity in their design and composition to exhibit reversible bidirectional motion determined by the field precession angle.   

In this review, we take a critical look at an emerging field that seeks to utilize active matter for therapeutics. The recent literature suggests that such particles could significantly augment present-day drug delivery, by enhancing transport and increasing permeability across anatomical barriers by transporting drugs within solid tumor microenvironments or disrupting cardiovascular plaque. We also discuss potential challenges, opportunities, and translational hurdles.  

We present a novel technique to measure the force output of thin film microactuators. Also, we develop and fabricate three designs of residual stress microactuators and use them to validate this technique, and establish a relationship between performance and design parameters. We find an inverse dependence of the thickness of the actuator and its force output and we anticipate that this microsystem measurement approach could be used for force measurements on alternate microactuators including shape memory, piezo and electromagnetic actuators.

This paper presents a novel solution to the problem of estimating and tracking the 3D position, orientation and configuration of the tips of submillimeter grippers from marker-less visual observations. We consider this as an optimization problem, which is solved using a variant of the Particle Swarm Optimization algorithm. We believe that the proposed technique can be applied to different stimuli responsive miniaturized agents, allowing the user to estimate the full configuration of complex agents from visual marker-less observations.

Here, it is demonstrated how helical nanomachines can be used to measure and map the local mechanical properties of a complex heterogeneous environment. The positions of the nanomachines are precisely controlled using externally applied magnetic fields, while their instantaneous orientations provide estimation of the viscosity of the surrounding medium with high spatial and temporal accuracy. The measurement technique can be applied to both Newtonian as well as shear thinning media, and all experimental results are in good agreement with the theoretical analysis. 

In this study, we design, manufacture, characterize, and control four similarly-structured semi-rigid thermoresponsive micro-grippers. Furthermore, we develop a closed loop-control algorithm to demonstrate and compare the performance of the said grippers when moving in hard-to-reach and unpredictable environments. Finally, we analyze the grasping characteristics of three of the presented designs.  Overall, not only does the study demonstrate motion control in unstructured dynamic environments but it also aims to provide quantitative data and considerations to help a targeted design of magnetically-controlled thin micro-grippers.

In this mini-review, untethered soft grippers are discussed, with an emphasis on a class of autonomous stimuli responsive gripping soft tools that can be used to excise tissues and release drugs in a controlled manner. The grippers are composed of polymers and hydrogels, and are thus compliant to soft tissues. They can be navigated using magnetic fields and controlled by robotic path-planning strategies to carry out tasks like pick-and-place of microspheres and biological materials either with user assistance or in a fully autonomous manner. It is envisioned that the use of these untethered soft grippers will translate from laboratory experiments to clinical scenarios and the challenges that need to be overcome to make this transition are discussed.

In this work we present the details of the numerical calculation to model their motion in the presence of thermal fluctuations. Also pertaining to their possible use in microfluidic devices, we have included the effect of adjacent walls. The results of our numerical calculations show non-Gaussian features in the power spectrum of the propulsion velocity, in close resemblance with experimental observations.

We used experimental observations and a numerical model to study the various fluctuation mechanisms that determine the performance of an externally driven helical propeller as the size of the helix is reduced. From causality analysis, an overwhelming effect of orientational noise at low length scales is observed, which strongly affects the average velocity and direction of motion of a propeller. For length scales smaller than a few micrometers in aqueous media, the operational frequency for the propulsion system would have to increase as the inverse cube of the size, which can be the limiting factor for a helical propeller to achieve locomotion in the desired direction.

We studied the formation of a wafer-scale network of connected colloidal beads by reactive ion etching. The dimensions of the connections have been studied as a function of etching time for colloidal beads of different sizes, and could be well controlled. The authors have found that the nano-network forms and disappears for the same time of etching independent of the diameter of the polystyrene beads. With recent interest of connected colloidal networks in various optical sensing applications, such as photonic crystals, as surface-enhanced Raman scattering substrates, the studies have potential uses in the development of wafer-scale nanophotonic sensors.

We report on a wafer scale fabrication method of a three-dimensional plasmonic metamaterial with strong chiroptical response in the visible region of the electromagnetic spectrum. The system was comprised of metallic nanoparticles arranged in a helical fashion, with high degree of flexibility over the choice of the underlying material, as well as their geometrical parameters. This resulted in exquisite control over the chiroptical properties, most importantly the spectral signature of the circular dichroism. The average chiro-optical response of the material remained uniform across the wafer, thus confirming the suitability of this system as a large area chiral metamaterial. 

We consider the rotational motion of an elongated nanoscale object in a fluid under an external torque. The experimentally observed dynamics could be understood from analytical solutions of the Stokes equation, with explicit formulae derived for the dynamical states as a function of the object dimensions and the parameters defining the external torque. Under certain conditions, multiple analytical solutions to the Stokes equations exist, which have been investigated through numerical analysis of their stability against small perturbations and their sensitivity towards initial conditions. These experimental results and analytical formulae could be useful in the design of non-spherical nanostructures for diverse applications pertaining to microfluidics and nanoscale propulsion technologies.

We study the motion of a ferromagnetic helical nanostructure under the action of a rotating magnetic field. A variety of dynamical configurations were observed that depended strongly on the direction of magnetization and the geometrical parameters, which were also confirmed by a theoretical model, based on the dynamics of a rigid body under Stokes flow. Although motion at low Reynolds numbers is typically deterministic, under certain experimental conditions the nanostructures showed a surprising bistable behavior, such that the dynamics switched randomly between two configurations, possibly induced by thermal fluctuations. The experimental observations and the theoretical results presented in this paper are applicable to any system of ellipsoidal symmetry under external force or torque.