Smart capsules for sensing and sampling the gut: status, challenges and prospects.

Smart capsules are developing at a tremendous pace with a promise to become effective clinical tools for the diagnosis and monitoring of gut health. This field emerged in the early 2000s with a successful translation of an endoscopic capsule from laboratory prototype to a commercially viable clinical device. Recently, this field has accelerated and expanded into various domains beyond imaging, including the measurement of gut physiological parameters such as temperature, pH, pressure and gas sensing, and the development of sampling devices for better insight into gut health. In this review, the status of smart capsules for sensing gut parameters is presented to provide a broad picture of these state-of-the-art devices while focusing on the technical and clinical challenges the devices need to overcome to realise their value in clinical settings. Smart capsules are developed to perform sensing operations throughout the length of the gut to better understand the body's response under various conditions. Furthermore, the prospects of such sensing devices are discussed that might help readers, especially health practitioners, to adapt to this inevitable transformation in healthcare. As a compliment to gut sensing smart capsules, significant amount of effort has been put into the development of robotic capsules to collect tissue biopsy and gut microbiota samples to perform in-depth analysis after capsule retrieval which will be a game changer for gut health diagnosis, and this advancement is also covered in this review. The expansion of smart capsules to robotic capsules for gut microbiota collection has opened new avenues for research with a great promise to revolutionise human health diagnosis, monitoring and intervention.

Optical microlever assisted DNA stretching.

Optical microrobotics is an emerging field that has the potential to improve upon current optical tweezer studies through avenues such as limiting the exposure of biological molecules of interest to laser radiation and overcoming the current limitations of low forces and unwanted interactions between nearby optical traps. However, optical microrobotics has been historically limited to rigid, single-body end-effectors rather than even simple machines, limiting the tasks that can be performed. Additionally, while multi-body machines such as microlevers exist in the literature, they have not yet been successfully demonstrated as tools for biological studies, such as molecule stretching. In this work we have taken a step towards moving the field forward by developing two types of microlever, produced using two-photon absorption polymerisation, to perform the first lever-assisted stretches of double-stranded DNA. The aim of the work is to provide a proof of concept for using optical micromachines for single molecule studies. Both styles of microlevers were successfully used to stretch single duplexes of DNA, and the results were analysed with the worm-like chain model to show that they were in good agreement.

Piezo-actuated parallel mechanism for biological cell release at high speed.

In this paper, a dynamic releasing approach is proposed for high-speed biological cell manipulation. A compact parallel mechanism for grasping and releasing microobjects is used to generate controllable vibration to overcome the strong adhesion forces between the end effector and the manipulated object. To reach the required acceleration of the end effector, which is necessary for the detachment of the target object by overcoming adhesion forces, vibration in the end effector is generated by applying sinusoidal voltage to the PZT actuator of the parallel mechanism. For the necessary acceleration, we focus on the possible range of the frequency of the PZT-actuator-induced vibration, while minimizing the amplitude of the vibration (14 nm) to achieve precise positioning. The effect of the air and liquid environments on the required vibration frequency for successful release is investigated. For the first time, release results of microbeads and biological cells are compared. Release of the biological cells with 100 % success rate suggests that the proposed active release method is an appropriate solution for adhered biological cells during the release task.

An Alternative Micro-Milling Fabrication Process for Rapid and Low-Cost Microfluidics.

Microfluidics is an important technology for the biomedical industry and is often utilised in our daily lives. Recent advances in micro-milling technology have allowed for rapid fabrication of smaller and more complex structures, at lower costs, making it a viable alternative to other fabrication methods. The microfluidic chip fabrication developed in this research is a step-by-step process with a self-contained wet milling chamber. Additionally, ethanol solvent bonding is used to allow microfluidic chips to be fully fabricated within approximately an hour. The effect of using this process is tested with quantitative contact profileometery data to determine the expected surface roughness in the microchannels. The effect of surface roughness on the controllability of microparticles is tested in functional microfluidic chips using image processing to calculate particle velocity. This process can produce high-quality channels when compared with similar studies in the literature and surface roughness affects the control of microparticles. Lastly, we discuss how the outcomes of this research can produce rapid and higher-quality microfluidic devices, leading to improvement in the research and development process within the fields of science that utilise microfluidic technology. Such as medicine, biology, chemistry, ecology, and aerospace.

Anchoring Mechanism for Capsule Endoscope: Mechanical Design, Fabrication and Experimental Evaluation.

Capsule endoscopes are widely used to diagnose gut-related problems, but they are passive in nature and cannot actively move inside the gut. This paper details the design process and development of an anchoring mechanism and actuation system to hold a capsule in place within the small intestine. The design centres around the mechanical structure of the anchor that makes use of compliant Sarrus linkage legs, which extend to make contact with the intestine, holding the capsule in place. Three variants with 2 legs, 3 legs and 4 legs of the anchoring mechanism were tested using a shape memory alloy spring actuator (5 mm × Ï• 3.4 mm). The experiments determine that all the variants can anchor at the target site and resist peristaltic forces of 346 mN. The proposed design is well suited for an intestine with a diameter of 19 mm. The proposed design allows the capsule endoscopes to anchor at the target site for a better and more thorough examination of the targeted region. The proposed anchoring mechanism has the potential to become a vital apparatus for clinicians to use with capsule endoscopes in the future.

Interfacial colloidal assembly guided by optical tweezers and tuned via surface charge.

HYPOTHESIS: The size, shape and dynamics of assemblies of colloidal particles optically-trapped at an air-water interface can be tuned by controlling the optical potential, particle concentration, surface charge density and wettability of the particles and the surface tension of the solution. EXPERIMENTS: The assembly dynamics of different colloidal particle types (silica, polystyrene and carboxyl coated polystyrene particles) at an air-water interface in an optical potential were systematically explored allowing the effect of surface charge on assembly dynamics to be investigated. Additionally, the pH of the solutions were varied in order to modulate surface charge in a controllable fashion. The effect of surface tension on these assemblies was also explored by reducing the surface tension of the supporting solution by mixing ethanol with water. FINDINGS: Silica, polystyrene and carboxyl coated polystyrene particles showed distinct assembly behaviours at the air-water interface that could be rationalised taking into account changes in surface charge (which in addition to being different between the particles could be modified systematically by changing the solution pH). Additionally, this is the first report showing that wettability of the colloidal particles and the surface tension of the solution are critical in determining the resulting assembly at the solution surface.

Inside the ensemble: unlocking the potential of one-at-a-time experiments with lab-on-a-chip automation.

The advent of technologies that allow the interactions of individual microscopic particles to be probed "one-at-a-time" has paved the way for new experimental avenues of enquiry in colloidal systems. For example, investigating whether a particular pair of colloidal particles isolated from a macroscopic sample might adhere to each other when brought into close proximity is certainly possible. However, given the probabilistic nature of the process (different particles within the ensemble may have slightly different surface charge distributions and asperities, and interaction energies involved can be close to thermal values), it is important that many hundreds or thousands of pairs of particles are tested under each set of experimental conditions of interest. Currently it is still an arduous task to perform such an experiment a sufficient number of times in order to acquire a data-set that truly represents the ensemble. Herein an automated particle collider for measuring particle-particle interactions has been realized by combining elements of microfluidics, holographic optical tweezers and image processing. Each individual measurement consists of confining two particles within a predetermined chemical micro-environment, and observing whether their interactions lead to aggregation. To automate the measurements, computer software consisting of LabVIEW and Red Tweezers with a custom plugin was used. Preliminary experiments carried out using 1 µm diameter polystyrene particles demonstrated that many hundreds of pairwise-interaction measurements could be carried out autonomously within a matter of hours. Further exemplar real-world experiments, designed to examine the stickiness of emulsion drops as a function of bulk measurements of the ζ-potential (zeta potential) of the sample, were then performed. It is envisaged that such robust approaches to the automation of "one-at-a-time" experiments will find applications in a large number of areas, and enable previously unthinkable experiments to be carried out in a timely fashion, thus allowing the focus to shift away from tedious experimental frustrations to more profound scientific questions.

Capsule robot for gut microbiota sampling using shape memory alloy spring.

BACKGROUND: Human gut microbiota can provide lifelong health information and even influence mood and behaviour. We currently lack the tools to obtain a microbial sample, directly from the small intestine, without contamination. METHODS: Shape memory alloy springs are used in concentric configuration to develop an axial actuator. A novel design of sampling mechanism is fabricated for collecting the sample from the gut. Storage chamber (500 µl) is used to protect the sample from downstream contamination. RESULTS: The developed actuator occupies a small space (5 × Ø5.75 mm) and produces sufficient output force (1.75 N) to operate the sampling mechanism. A non-invasive capsule robot was tested ex vivo on the animal intestine, and it captured an average of 134 µl content which was sufficient for microbiome assessment. CONCLUSIONS: Laboratory testing revealed that the collected sample had an amino acid signature indicative of microbiota, mucus and digesta, which provided a proof of concept for the proposed design.

Optical Micromachines for Biological Studies.

Optical tweezers have been used for biological studies since shortly after their inception. However, over the years research has suggested that the intense laser light used to create optical traps may damage the specimens being studied. This review aims to provide a brief overview of optical tweezers and the possible mechanisms for damage, and more importantly examines the role of optical micromachines as tools for biological studies. This review covers the achievements to date in the field of optical micromachines: improvements in the ability to produce micromachines, including multi-body microrobots; and design considerations for both optical microrobots and the optical trapping set-up used for controlling them are all discussed. The review focuses especially on the role of micromachines in biological research, and explores some of the potential that the technology has in this area.

Development of a Novel Modular Compliant Gripper for Manipulation of Micro Objects.

This paper proposes a modular gripping mechanism for the manipulation of multiple objects. The proposed micro gripper combines traditional machining techniques with MEMS technologies to produce a modular mechanism consisting of a sturdy, compliant aluminium base and replaceable end-effectors. This creates an easily-customisable solution for micro manipulation with an array of different micro tips for different applications. We have provided the kinematic analysis for the gripper to predict the output and have also optimised design parameters based on FEA (finite element analysis) simulation and the effects of altering flexure beam lengths. The gripper is operated by a piezo actuator capable of 18 µ m displacement at 150 V of applied DC voltage. This is then amplified by a factor of 8.1 to a maximum tip displacement of 154 µ m. This is achieved by incorporating bridge and lever amplifying techniques into the design. An initial experimental analysis of the micro gripper is provided to investigate the performance of the micro gripper and to gauge the accuracy of the theory and simulation through comparison with experimental results.

Micromanipulation System for Isolating a Single Cryptosporidium Oocyst.

In this paper, an integrated system for contact micromanipulation of Cryptosporidium oocysts is presented. The system integrates five actuators and a partially automated control system and contacts the oocyst using a drawn glass end effector with tip dimensions of 1 µ m. The system is intended to allow single cell analysis (SCA) of Cryptosporidium-a very harmful parasite found in water supplies-by isolating the parasite oocyst of 5 µ m diameter in a new environment. By allowing this form of analysis, the source of Cryptosporidium can be found and potential harm to humans can be reduced. The system must overcome the challenges of locating the oocysts and end effector in 3D space and contact adhesion forces between them, which are prominent over inertial forces on this scale. An automated alignment method is presented, using the Prewitt operator to give feedback on the level of focus and this system is tested, demonstrating alignment accuracy of <2 µ m. Moreover, to overcome the challenge of adhesion forces, use of dry and liquid environments are investigated and a strategy is developed to capture the oocyst in the dry environment and release in the liquid environment. An experiment is conducted on the reliability of the system for isolating a Cryptosporidium oocyst from its culture, demonstrating a success rate of 98%.