Microinjection is usually applied to the treatment of some retinal disorders, such as retinal vein cannulation and displaced submacular hemorrhage. Currently, the microinjection procedure is usually performed by using the viscous fluid control of a standard vitrectomy system, which applies a fixed air pressure through foot pedal activation. The injection process with the fixed pressure is uncontrollable and lacks feedback, the high flow rate of the injected drug may cause damage to the fundus tissue. In this paper, a liquid-driven microinjection system with a flow sensor is designed and developed specifically for fundus injection. In addition, a PID sliding mode control (SMC) method is proposed to achieve precise injection in the injection system. The experimental results of fundus simulation injection demonstrate that the microinjection system meets the requirements of fundus injection and reduces the impact of the injection process on the fundus tissue.

Retinal vein cannulation (RVC) is a surgical procedure utilized in the treatment of retinal vein occlusion. During RVC, the micropuncture process encounters challenges due to unstable contact between the bent needle and the retinal vein, potentially resulting in micropuncture failure. To enhance the success rate, a robotic micropuncture procedure with preload strategy is proposed, which can increase the tissue stiffness and improve stability. First, a nonlinear viscoelastic (NV) model is developed to characterize the nonlinearity and relaxation behavior of the preload force. Subsequently, an NV model based adaptive integral terminal sliding mode controller (NAITSMC) is designed to ensure precise force tracking under tissue uncertainty and respiratory motion. The effectiveness of the robotic micropuncture is validated through in vitro experiments conducted on open-sky porcine eyes. The experimental results indicate that the NV model is more suitable for modeling the force applied to the retinal vein under various inner pressure cases. Under simulated respiratory motion, the NAITSMC demonstrates statistically reduction in error compared to the advanced sliding mode force controller. The preload strategy significantly improves the success rate, achieving a maximum rate of 90%. Furthermore, a preload force of 40 μN is recommended, demonstrating a higher success rate while maintaining acceptable safety considerations.

In recent years, the perforated patch clamp technique has been widely applied in cellular electrophysiology research due to its low mechanical disturbance and almost no loss of cellular content in cell membrane perforation process. However, the current passive release process of perforating materials prolongs the perforation process and easily disturbs the gigaseal formation process, significantly lowering the efficiency of perforated patch clamp operation. Addressing this, a robotic perforated patch clamp system was developed based on the active release control of perforating materials in this paper. First, a novel holding module of the patch micropipette integrated with an independently driven transmission channel of the perforating materials was developed for the first time. Then, through release tests of the perforating materials, the appropriate drive mode of transmission channel was determined to be the hydraulic mode with a faster response and higher stability. Further, the concentration gradient field of the perforating materials at the opening of the channel was modeled according to Fick’s law to prevent the false release of them in gigaseal formation process. Furthermore, a cell circuit model was developed to detect perforation degree online for feedback control of the perforating materials release. Experimental results on pyramidal neurons in mouse brain slices demonstrated that, in comparison to the traditional method with passive releases of perforating materials, the proposed system was capable of perforating cell membrane at an almost doubled throughput and with a 57% improvement in the success rate. In comparison to the traditional non-perforated whole-cell patch clamp method, the signal recording duration of neurons operated by our method was doubled due to its fewer negative influences on gigaseal and almost no cellular content loss. Note to Practitioners —The perforated patch clamp technique, utilizes the cell membrane-perforating molecules to drill subnanometer-sized conductive pores in the cell membrane aspirated into a micropipette for the measurement of cellular electrophysiological signals. Unfortunately, the poor controllability of the current passive release of perforating materials in the patch clamp operation easily leads to a long drug diffusion process, and also, disturbs the gigaseal formation between the aspirated cell membrane and micropipette, which is required for the measurement of the extremely weak cellular electrophysiological signals. For the first time, an active release control method of perforating materials was developed in this paper based on the self-developed novel three-channel holding device. With active release control of perforating materials, the proposed method was capable of perforating cell membranes at a doubled speed with a significantly higher success rate, and doubled recording duration in comparison to the traditional perforated patch clamp methods and non-perforated whole-cell patch clamp method, respectively, due to its fewer negative influences on gigaseal and almost no cellular content loss. With the above advantages, our robotic perforated patch clamp method may be applied in cellular electrophysiology research in the future.

Retinal vein occlusion (RVO) is a prevalent ocular pathology that may result in hemorrhage and even blindness. Currently, a procedure termed retinal vein cannulation (RVC), involving puncturing the retinal vein and injecting medication, has been developed. However, RVC requires extremely high precision at the micron scale. To address the challenges in the micro-puncturing process of the RVC, an adaptive finite-time sliding mode (AFSM) control scheme with a smooth motion generator has been proposed to assist surgeons in achieving precise micro-punctures using a piezo-actuated stage. Firstly, an S-curve-based smooth motion planning approach incorporating force feedback is designed to detect the successful micro-puncture state, thus addressing the challenge of limited force perception during the procedure. Subsequently, an AFSM control scheme has been developed to track the desired motion. Finally, a micro-puncture system, equipped with a silicon phantom, is established for experimental purposes. The experimental results demonstrate that the proposed control scheme significantly enhances the tracking performance during the micro-puncture process. The smooth motion planning and AFSM control scheme prove to be effective for the automatic control of the piezo-actuated end-effector, thereby providing improved assistance to surgeons in the RVC process. Note to Practitioners —During the procedure of retinal vein micro-puncture, it is crucial to ensure a smooth motion planning and accurate tracking to guide the needle tip into the retinal vein lumen. In light of the difficulties in lack of depth perception, a motion generator has been proposed with an adaptive micro-puncture state detection mechanism based on force feedback. To reliably track the desired motion, the AFSM controller is designed to ensure tracking accuracy and robustness, and finite-time stability. In particular, the adaptive gain of the AFSM controller does not require uncertain prior information, making it friendly to clinical applications. The experimental results based on silicone phantom, demonstrate the effectiveness of the controller in achieving successful micro-puncture with precise tracking performance. The implementation of the AFSM controller enables the automated micro-puncture task, reducing the risk of damage during operation.