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1 Recent Research Projects: 1. Musical Tuning Enhanced In-Vitro Micro/Nano Palpation of Cells: A Multi- Modal and Interactive System Engineering Approach for Cellular Pathology Studies Project Summary: In-vitro micro-/nano-mechanical studies have shown that cultured cancer cells are elastically softer than normal (healthy) cells, and new measurements on cells from cancer patients suggest that this mechanical signature or mechanical bio-marker can be a powerful means to detect cancer in the clinic or to explore new effective medications that treat cancers without killing normal cells in chemotherapy. The proposed research is to create a musical tuning enhanced in-virto micro/nano palpation system that will help to intuitively & interactively identify (by hearing) the mechanical signature or bio-marker of both cancer and normal cells, as illustrated in Fig. 1. This research takes the concept of acoustic stethoscope and applies it to intuitively understand clues between micro/nano mechanical properties change and pathology of cells through humans multi-modal perception capabilities. Fig. 1: Conceptual illustration of musical tuning enhanced micro/nano palpation. Fig. 2: Musical tuning enhanced micro/nano palpation on the grapefruit juice vesicles.

2 2. Durable and Cost-effective 3-D Microforce Sensor using Highly Sensitive Hybrid Piezoresistive Film Project Summary: The research is to develop low-cost, durable, and highly sensitive 3-D microforce sensors using the ultrasensitive hybrid carbon/polymer-based piezoresistive (HCP) film. Fig. 3 illustrates the developed cross-shaped flexible HCP beam microforce sensor with self-decoupling mechanism. Extensive calibration and experimental results demonstrate that the sensor is cost-effective and durable, and the resolution can reach 10 nano Newton. Fig. 3: Illustration of the parallel structured 3-D microforce sensor design. Fig. 4: Film force calibration using Femto FT-S540* Fig. 5: Deformation simulation and stress/strain analysis results using AnSYS Fy--Fx decoupling Fx--Fy decoupling Fz--Fx+Fy decoupling Fig. 6: Experimental Results on 3-D Self-decoupling. (Measured and calibrated by FGV-1XY digital force sensor)

3 3. Dynamically Characterizing Bioimpedance of Fingertip Skin Through a Developed Constant Voltage Driver (CVD) Based Electrotactile Rendering System Project Summary: This research focuses on dynamically characterizing parameters of the resistor-capacitor (R-C) load bioimpedance model of fingertip skin through a custom-built constant-voltage-driver (CVD) based electrotactile rendering system and an embedded on-line identification method. The goal of our work is to better understand these dynamic characteristics and utilizes them to automatically tune the stimulation voltage or current to a desired sensation level for different users. The electrotactile mechanism is illustrated in Fig. 7. Fig. 7: (a) Mechanism of electrotactile stimulation. (b) Tactile receptors in human skin. The dynamic characterization of bioimpedance parameters of fingertip skin was successfully implemented through a custom-built CVD electrotactile rendering system embedded with an on-line identification algorithm. Fig. 8: The first-order bioimpedance model of fingertip skin under electrotactile stimulation Fig. 9: On-line bioimpedance identification results.

4 Fig. 10: Dynamic ranges and power output of the CVD electrotactile rendering. 4. An Optical Surface Characterization Sensor for Simultaneously Measuring Both 3-D Surface Texture and Mechanical Properties Project Summary: Among current non-contact and contact based surface characterization technologies, none can stand out to simultaneously and rapidly measure both surface patterns/textures and mechanical properties such as softness, friction, and mechanical impedance. This project is to develop a surface characterization sensor that combines both contact and non-contact optical surface profiling mechanisms, and can be used for quantitative characterization of soft material surface texture properties including 3-D texture pattern, roughness, and even mechanical properties like softness, etc. Fig. 11 illustrates the sensor design. Fig. 11: Illustration of the optical 3-D surface characterization sensor. LS 1 LS 2 LS 3 Fig. 12: Characterization results of 3 Leather Samples (LS1~LS3): raw (a) and enhanced (b) 2-D surface textures, (c) 3-D surface textures, (d) relative softness graphs, and (e) roughness graphs.

5 5. Enhancing Measurement Accuracy of Position Sensitive Detector (PSD) Systems Using the Averaging Filter and Distortion Rectifying Project Summary: Factors affecting measurement accuracy of Position Sensitive Detector (PSD) systems consist of inaccuracies caused by interface circuits, system connection, outside environment change, and the semi-conductive properties of the sensor. The presence of these factors causes noises and distortions that are interpreted as a valid signal by the PSD system. As a result, these inaccuracies heavily degrade the PSD performance and hamper the measurement resolution and accuracy of the PSD systems, which greatly limit its applications in micro/nano positioning. This research project aims at enhancing measurement accuracy of PSD sensing systems, as shown in Fig. 13. After implementation of the developed algorithms and approaches including the averaging filtering, the coordinates mismatch correction, and the distortion rectifying, the measurement accuracy in a large active area of the PSDs is significantly improved. The research outcome is being extended to numerous applications, e.g., a new scanning PSD microscopy system. Fig. 13: Illustration of laser-psd system with interfaces Fig. 14: Noise sources and noise reduction through the developed filtering method Fig. 15: Results of distortion rectifying

6 PSD mapping with three circles (blue: reference) PSD mapping with Archimedean spiral (blue: reference) Fig. 16: PSD Mapping Results after the enhancement. Both mapping errors in x and y within the range of 1 mm are less than 3%. 6. Networked Brain-Driven Micro-Biomanipulation with High-Resolution Mind Traces Tracking and Multi-Sensing Feedback Project Summary: This research project aims at developing an integrated brain-driven micro-biomanipulation platform that can perform mind-controlled bio-medical operation tasks at micro/nano scale via high-speed network, as shown in Fig. 17. The developed platform can be effectively used to investigate manipulation behavior and neuro-biofeedback mechanism of human brain, so as to facilitate developing high-efficiency micro-bio-manipulation strategy of engineering approaches in micro/nano level. The research work will further impact related life-science research such as genetics, drug discovery, and neuroscience through integrating human thinking and decision-making faculties with life-science instruments. Project Fig. Results: 17: Overview of mind-controlled micro-biomanipulation platform

7 Fig. 18: Results of 2-D position control (left) and path tracking (right) by human mind. Fig. 19: Results of a full 2-D mind motion Tracking based on two gyro sensing feedback. Fig. 20: An experimental example demonstrating mind-controlled micro-biomanipulation on a bio-sample.

8 7. Quantitative Mechanical Evaluation and Analysis of Drosophila Embryos through the Stages of Embryogenesis Using a Sensorized Human/Robot Cooperative Interface Project Summary: To better understand the biomechanical properties involved in Drosophila embryo research, this work presents a mechanical characterization of living Drosophila embryos through the stages of embryogenesis. Measurement of the mechanical properties of Drosophila embryos is implemented using a networked human/robot cooperative interface featuring a novel, in situ, and minimally invasive piezoelectric force-sensing tool with resolution in the range of μn. Penetration force profiles of the embryos at various stages of embryogenesis are reported. The Young s modulus, stiffness, and the mechanical impedance of the developing Drosophila embryos are quantitatively evaluated and presented alongside experimentally derived mathematical models. Fig. 21 demonstrates the sequence of images showing the embryonic penetration using the sensor tip during the mechanical evaluation. Fig. 21: A sequence of images showing the embryonic penetration using the sensor tip during the mechanical characterization. (a) (b) (c) Fig. 22: Force profiles of the microinjection process at distinctive stages of embryogenesis. (a) Stage 6 (Gastrulation), (b) Stage 12 (Germ band retraction), (c) Stage 14~15 (Head involution and dorsal closure).

9 Fig. 23: The Applied Hertz-Sneddon contact model. (a) (b) (c) Fig. 24: Histogram of extracted Young s Moduli (a), stiffness (b), and mechanical impedance (c) at progressing stages of embryogenesis.

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