Viet Ha Le

Shape memory alloy–based biopsy device for active locomotive intestinal capsule endoscope

Recently, capsule endoscopes have been used for diagnosis in digestive organs. However, because a capsule endoscope does not have a locomotive function, its use has been limited to small tubular digestive organs, such as small intestine and esophagus. To address this problem, researchers have begun studying an active locomotive intestine capsule endoscope as a medical instrument for the whole gastrointestinal tract. We have developed a capsule endoscope with a small permanent magnet that is actuated by an electromagnetic actuation system, allowing active and flexible movement in the patient’s gut environment. In addition, researchers have noted the need for a biopsy function in capsule endoscope for the definitive diagnosis of digestive diseases. Therefore, this paper proposes a novel robotic biopsy device for active locomotive intestine capsule endoscope. The proposed biopsy device has a sharp blade connected with a shape memory alloy actuator. The biopsy device measuring 12mm in diameter and 3mm in length was integrated into our capsule endoscope prototype, where the device’s sharp blade was activated and exposed by the shape memory alloy actuator. Then the electromagnetic actuation system generated a specific motion of the capsule endoscope to extract the tissue sample from the intestines. The final biopsy sample tissue had a volume of about 6mm3, which is a sufficient amount for a histological analysis. Consequently, we proposed the working principle of the biopsy device and conducted an in-vitro biopsy test to verify the feasibility of the biopsy device integrated into the capsule endoscope prototype using the electro-magnetic actuation system.

Nanohybrid magnetic liposome functionalized with hyaluronic acid for enhanced cellular uptake and near-infrared-triggered drug release

The aim of this work is to prepare and evaluate a novel lipid-polymer hybrid liposomal nanoplatform (hyaluronic acid-magnetic nanoparticle-liposomes, HA-MNP-LPs) as a vehicle for targeted delivery and triggered release of an anticancer drug (docetaxel, DTX) in human breast cancer cells. We first synthesize an amphiphilic hyaluronic acid hexadecylamine polymer (HA-C16) to enhance the targeting ability of the hybrid liposome. Next, HA-MNP-LPs are constructed to achieve an average size of 189.93±2.74nm in diameter. In addition, citric acid-coated magnetic nanoparticles (MNPs) are prepared and embedded in the aqueous cores while DTX is encapsulated in the hydrophobic bilayers of the liposomes. Experiments with coumarin 6 loaded hybrid liposomes (C6/HA-MNP-LPs) show that the hybrid liposomes have superior cellular uptake in comparison with the conventional non-targeting liposomes (C6/MNP-LPs), and the result is further confirmed by Prussian blue staining. Under near-infrared laser irradiation (NIR, 808nm), the HA-MNP-LPs aqueous solution can reach 46.7°C in 10min, and the hybrid liposomes released over 20% more drug than the non-irradiated liposomes. Using a combination of photothermal irradiation and chemotherapy, the DTX-loaded hybrid liposomes (DTX/HA-MNP-LPs) significantly enhance therapeutic efficacy, with the IC50 value of 0.69±0.10μg/mL, which is much lower than the values for DTX monotherapy. Consequently, the prepared hybrid nanoplatform may offer a promising drug delivery vehicle with selective targeting and enhanced drug release in treating CD44-overexpressing cancers.

Manipulation of tumor targeting cell-based microrobots carrying NIR light sensitive therapeutics using EMA system and chemotaxis

In this study, we prepare and evaluate a novel cellbased micro-platform (microrobot) for active tumor therapy. The microrobots are fabricated utilizing the engulfment activity of immune cells (macrophages) with drug-loaded magnetic liposomes via phagocytosis. First, we synthesize magnetic nanoparticles (MNP) with superparamagnetic properties and high energy absorbance to near-infrared (NIR) light, and load the MNPs to liposomes (MNP-DLs). Then, we prepare the microrobots by incubating the MNP-DLs with the macrophages. After that, we characterize the tumor targeting ability of the microrobots using electromagnetic actuating (EMA) system and a transwell chemotactic assay. Experiment results show that the microrobots can be controlled by an external magnetic field to reach the average velocity of approximately 11 μm/second, and they can cross the membranes mimicking the blood barrier to tumor chemo-attractants with the infiltration rate up to 74%. Therefore, the study proposes an innovative approach for active tumor targeting and NIR light triggered drug delivery using the developed cellular microrobots.

Novel active locomotive capsule endoscope with micro-hydraulic pump for drug delivery function

This paper presents a novel mechanism and design of capsule endoscope in order to perform an active locomotive capsule endoscope (ALICE) robot integrated with micro-hydraulic pump for drug delivery function. The proposed locomotive capsule endoscope can actively move and investigate in gastrointestinal tract, powered externally by an electro-magnetic actuation (EMA) system. To perform a drug pumping function, the rotating frequency of the active hydraulic pump can be adjusted by the EMA system. The novel capsule endoscope with the micro-hydraulic pump is focused on target drug delivery function. The capsule endoscope is able to target suspicious region and release controllable amount of drug. Through preliminary tests of the locomotive capsule endoscope with the micro-pump, the feasibility of the locomotion and the drug releasing of the novel capsule endoscope will be presented. The micro-hydraulic pump for a drug delivery function will be a potential component for a future capsule endoscope with active maneuverability, diagnostic and therapeutic functions.

Effect of Chitosan on Motility of Bacteria-Driven Liposomal Microrobots

This study proposes a prototype of bacteria-based microrobots using chitosan-coated liposomes attached to a Salmonella enteritidis bacterial strain. The attachment of the liposome and the bacteria is performed by interaction between the positive charge surface of the liposomes and the gram-negative bacteria. The liposomes are fabricated using hydration method to obtain the average diameter of 10 um and they are coated with chitosan. The chitosan coating is shown to have effect on motility of the microrobots. First, the bacteria cannot attach to chitosan-uncoated liposomes, but they can easily adhere to the chitosan-coated liposomes. Second, when the concentration of chitosan increases from 0.1% to 0.5%, average velocity of the microrobots increases from 1.20±0.12 um/s to 3.25±0.35 um/s. However, when chitosan concentration increases to 1% the average velocity of the microrobots slightly decreases from 3.25±0.35 um/s to 3.17±0.33 um/s, respectively. The study suggests that using chitosan coating can be a potential method for further development of therapeutic bacteria-based liposomal microrobots.

Feasibility study of electromagnetic guidance system for intestinal capsule endoscope

Owing to some limitations (uncomfortable procedure, pains, and side effects of anesthetic drug) of a conventional flexible endoscope in gastrointestinal diagnostic procedure, the capsule endoscope was invented and released as an alternative. In spite of many benefits of the capsule endoscope, however, it has been limited used only for esophagus and small intestine because of its mobility deficiency in the diagnosis. Therefore, in order to expand the applicable fields of the capsule endoscopy into stomach and colon, the mobility function such as 3-dimensional (D) locomotion of the capsule endoscope is indispensable. Previously, some researchers proposed the mobility mechanisms of the capsule endoscope. However, they could not realize sufficiency DOF (degree of freedom) and not show various motions of the capsule endoscope. In this paper, therefore, we propose a novel electromagnetic actuation (EMA) system which can operate 3-D locomotion of a capsule endoscope in the digestive organs. The proposed electromagnetic actuation system for guiding magnetic capsule endoscope, comprised of 5-pairs of solenoid coils and a capsule endoscope with a small magnet. By the electromagnetic field which is operated from the EMA system using the five pairs of solenoid coils, the capsule endoscope can show diverse motions for the diagnosis of gastrointestinal tract like as propulsion to any direction, steering and helical motion. Through a locomotion test, we confirm that ALICE can show the tracking angle error under 4 degrees. In addition, to verify the feasibility of ALICE as a real diagnostic device, a real camera and a FPV (First-person Point of View) control interface are integrated with ALICE. Consequently, through the basic mobility test and the in-vitro test, we verify the feasibility of ALICE system as a medical endoscopic device

ACTIVE CAPSULE ENDOSCOPE MICRO-ROBOT WITH BIOPSY TOOLS

This paper presents an active locomotive intestinal capsule endoscope as a micro-robot that travel into the digestion system with wireless control abilities. The capsule endoscope is integrating with novel micro-biopsy tools to be able to extract tissue samples from the small and larger intestine. The entirely capsule system has abilities of target random biopsies by localization method, coming to right place to take biopsy sample, take and send several hundred of pictures for further analysis by the doctor. The biopsy mechanism provides passive triggered mechanism with highly active positional accuracy to collect the biopsy tissue sample and control along the way of the intestine.

Ferrofluid soft-robot bio-inspired by Amoeba locomotion

This paper presents a novel application based on the bio-inspired motion of the Amoeba. This research is focused on development a soft micro robot based on the Amoeba locomotion which can be named Whole Skin Locomotion. The robot is created using the fluid filled toroid method that acts as a body shaping feature with ferrofluid material placed within that is delivered to create the driving force. The passive fluid switch acts as an active sensitive liquid when a magnetic field is applied. Therefore, based on this behaviour in order to produce the driving motion external Electromagnetic coils are arranged as a wireless control and actuator. A number of motions and hindrances are currently presented to insure the principal motions of the robot. Some other approaches of ferrofluid soft-robot biomimetic inspired are also presented as well.