3D particle-based cell modelling for haptic microrobotic cell injection

Introducing haptic interface to conduct microrobotic intracellular injection has many beneficial implications. In particular, the haptic device provides force feedback to the bio-operator\u27s hand. This paper introduces a 3D particle-based model to simulate the deformation of the cell membrane and corresponding cellular forces during microrobotic cell injection. The model is based on the kinematic and dynamic of spring – damper multi particle joints considering visco-elastic fluidic properties. It simulates the indentation force feedback as well as cell visual deformation during the microinjection. The model is verified using experimental data of zebrafish embryo microinjection. The results demonstrate that the developed cell model is capable of estimating zebrafish embryo deformation and force feedback accurately

Haptic guidance for microrobotic intracellular injection

The ability for a bio-operator to utilise a haptic device to manipulate a microrobot for intracellular injection offers immense benefits. One significant benefit is for the bio-operator to receive haptic guidance while performing the injection process. In order to address this, this paper investigates the use of haptic virtual fixtures for cell injection and proposes a novel force field virtual fixture. The guidance force felt by the bio-operator is determined by force field analysis within the virtual fixture. The proposed force field virtual fixture assists the bio-operator when performing intracellular injection by limiting the micropipette tip\u27s motion to a conical volume as well as recommending the desired path for optimal injection. A virtual fixture plane is also introduced to prevent the bio-operator from moving the micropipette tip beyond the deposition target inside the cell. Simulation results demonstrate the operation of the guidance system.<br /

Virtual haptic cell model for operator training

Microrobotic cell injection is an area of growing research interest. Typically, operators rely on visual feedback to perceive the microscale environment and are subject to lengthy training times and low success rates. Haptic interaction offers the ability to utilise the operator&rsquo;s haptic modality and to enhance operator performance. Our earlier work presented a haptically enabled system for assisting the operator with certain aspects of the cell injection task. The system aimed to enhance the operator&rsquo;s controllability of the micropipette through a logical mapping between the haptic device and microrobot, as well as introducing virtual fixtures for haptic guidance. The system was also designed in such a way that given the availability of appropriate force sensors, haptic display of the cell penetration force is straightforward. This work presents our progress towards a virtual replication of the system, aimed at facilitating offline operator training. It is suggested that operators can use the virtual system to train offline and later transfer their skills to the physical system. In order to achieve the necessary representation of the cell within the virtual system, methods based on a particle-based cell model are utilised. In addition to providing the necessary visual representation, the cell model provides the ability to estimate cell penetration forces and haptically display them to the operator. Two different approaches to achieving the virtual system are discussed

Haptic microrobotic intracellular injection assistance using virtual fixtures

In manual cell injection the operator relies completely on visual information for task feedback and is subject to extended training times as well as poor success rates and repeatability. From this perspective, enhancing human-in-the-loop intracellular injection through haptic interaction offers significant benefits. This paper outlines two haptic virtual fixtures aiming to assist the human operator while performing cell injection. The first haptic virtual fixture is a parabolic force field designed to assist the operator in guiding the micropipette\u27s tip to a desired penetration point on the cell\u27s surface. The second is a planar virtual fixture which attempts to assist the operator from moving the micropipette\u27s tip beyond the deposition target location inside the cell. Preliminary results demonstrate the operation of the haptically assisted microrobotic cell injection system

A Fully Automated Robotic System for Microinjection of Zebrafish Embryos

As an important embodiment of biomanipulation, injection of foreign materials (e.g., DNA, RNAi, sperm, protein, and drug compounds) into individual cells has significant implications in genetics, transgenics, assisted reproduction, and drug discovery. This paper presents a microrobotic system for fully automated zebrafish embryo injection, which overcomes the problems inherent in manual operation, such as human fatigue and large variations in success rates due to poor reproducibility. Based on computer vision and motion control, the microrobotic system performs injection at a speed of 15 zebrafish embryos (chorion unremoved) per minute, with a survival rate of 98% (n = 350 embryos), a success rate of 99% (n = 350 embryos), and a phenotypic rate of 98.5% (n = 210 embryos). The sample immobilization technique and microrobotic control method are applicable to other biological injection applications such as the injection of mouse oocytes/embryos and Drosophila embryos to enable high-throughput biological and pharmaceutical research

Novel parameter estimation schemes in microsystems

This paper presents two novel estimation methods that are designed to enhance our ability of observing, positioning, and physically transforming the objects and/or biological structures in micromanipulation tasks. In order to effectively monitor and position the microobjects, an online calibration method with submicron precision via a recursive least square solution is presented. To provide the adequate information to manipulate the biological structures without damaging the cell or tissue during an injection, a nonlinear spring-mass-damper model is introduced and mechanical properties of a zebrafish embryo are obtained. These two methods are validated on a microassembly workstation and the results are evaluated quantitatively

Mechanical Property Characterization of Mouse Zona Pellucida

Previous intracytoplasmic sperm injection (ICSI) studies have indicated significant variation in ICSI success rates among different species. In mouse ICSI, the zona pellucida (ZP) undergoes a hardening process at fertilization in order to prevent subsequent sperm from penetrating. There have been few studies investigating changes in the mechanical properties of mouse ZP post fertilization. To characterize mouse ZP mechanical properties and quantitate the mechanical property differences of the ZP before and after fertilization, a microelectromechanical systems-based multiaxis cellular force sensor has been developed. A microrobotic cell manipulation system employing the multiaxis cellular force sensor is used to conduct mouse ZP force sensing, establishing a quantitative relationship between applied forces and biomembrane structural deformations on both mouse oocytes and embryos. An analytical biomembrane elastic model is constructed to describe biomembrane mechanical properties. The characterized elastic modulus of embryos is 2.3 times that of oocytes, and the measured forces for puncturing embryo ZP are 1.7 times those for oocyte ZP. The technique and model presented in this paper can be applied to investigations into the mechanical properties of other biomembranes, such as the plasma membrane of oocytes or other cell types

MILiMAC:Flexible Catheter With Miniaturized Electromagnets as a Small-Footprint System for Microrobotic Tasks

Advancements in medical microrobotics have given rise to an abundance of agents capable of localised interaction with human body in small scales. Nevertheless, clinically-relevant applications of this technology are still limited by the auxiliary infrastructure required for actuation of micro-agents. In this letter, we approach this challenge. Using finite-element analysis, we show that miniaturization of electromagnets can be used to create systems capable of providing magnetic forces adequate for micro-agent steering, while retaining small footprint and power consumption. We use these observations to create MILiMAC (Microrobotic Infrastructure Loaded into Magnetically-Actuated Catheter). MILiMAC is a flexible catheter employing three miniaturized electromagnets to provide localized magnetic actuation at the deeply-seated microsurgery site. We test our approach in a proof-of-concept study deploying MILiMAC inside a test platform to deliver and steer a 600 [\boldsymbol{\mu }m] ferromagnetic microbead. The bead is steered along a set of user-defined trajectories using closed-loop position control. Across all trajectories the best performance metrics are the mean error of 0.41 [mm] and the steady-state error of 0.27 [mm]