The presented work is concerned with the development and application of an ultrasonic detection scheme suitable for the monitoring of muscle dynamics with high temporal - down to 5 µs - and spatial resolution - down to 0.78 µm. A differential detection scheme has been developed to monitor the variations of the velocity of longitudinal polarized ultrasound waves travelling in contracting and relaxing muscle, compensating for variations of the path length by referencing to a frame. The observed time dependent variations of the time-of-flight of the ultrasonic waves caused by variations in the muscle and in addition by minor deformations of the enclosure are detected each separately and synchronously and are evaluated differentially. Beside of the detected increase of the speed of sound observed for contracted muscle with respect to the relaxed state of about 0.6%, the recovery time from maximum isometric contraction is quantified and relaxation processes are observed for the recovery phase following the isometric contraction. The developed ultrasonic calliper was employed to monitor both, the brain controlled and externally excited muscle dynamics with sampling intervals down to 10 ms synchronously with signals relating to the excitation. Monitored are the activation, hold, and relaxation phase for maximum voluntary isometric contraction of the gastrocnemius muscle. A so far not reported post tetanus overshoot and subsequent exponential recovery are observed. Both are attributed to the muscle as suggested by combined monitoring with EMG and are modelled with a lumped mechanical circuit containing an idealized bidirectional linear motor unit, ratchet, damper, and springs. Both, the rapid contraction and relaxation phases require a high order filter or alternatively a kernel filter, attributed to the nerve system as suggested by external electric stimulation. The respective response function is modelled by an electrical lumped circuit. Together with a reaction time and occasionally observed droops in the hold phase, both adjusted empirically, the monitored response is represented in close approximation by the combined electrical and mechanical lumped circuits. The respectively determined model parameters provide a refined evaluation scheme for the performance of monitored athletes. Valuable parameters relate to the latent period, the muscle response time, the activation and deactivation dynamics, a possible droop and other instabilities of the hold phase, and parameters characterizing the relaxation phase including the observed post tetanus overshoot and subsequent contraction. Monitored and modelled are also the different processes involved in active muscle dynamics including isotonic, isometric, and eccentric contraction or stretching. The developed technology provides time sequential observation of these processes and registration of their path in the extension and force parameter space. Under suitable conditions the closed-loop cycles of mind controlled human muscle movements proceed along characteristic lines coinciding with well identifiable elementary processes. The presentation of the monitored processes in the extension and force parameter space allows the determination of the mechanical energy expenditure for the observed different muscle actions. An elementary macroscopic mechanical model has been developed, suitable to express the basic features of the monitored muscle dynamics.

The presented work is concerned with the development and application of an ultrasonic detection scheme suitable for the monitoring of muscle dynamics with high temporal - down to 5 µs - and spatial resolution - down to 0.78 µm. A differential detection scheme has been developed to monitor the variations of the velocity of longitudinal polarized ultrasound waves travelling in contracting and relaxing muscle, compensating for variations of the path length by referencing to a frame. The observed time dependent variations of the time-of-flight of the ultrasonic waves caused by variations in the muscle and in addition by minor deformations of the enclosure are detected each separately and synchronously and are evaluated differentially. Beside of the detected increase of the speed of sound observed for contracted muscle with respect to the relaxed state of about 0.6%, the recovery time from maximum isometric contraction is quantified and relaxation processes are observed for the recovery phase following the isometric contraction. The developed ultrasonic calliper was employed to monitor both, the brain controlled and externally excited muscle dynamics with sampling intervals down to 10 ms synchronously with signals relating to the excitation. Monitored are the activation, hold, and relaxation phase for maximum voluntary isometric contraction of the gastrocnemius muscle. A so far not reported post tetanus overshoot and subsequent exponential recovery are observed. Both are attributed to the muscle as suggested by combined monitoring with EMG and are modelled with a lumped mechanical circuit containing an idealized bidirectional linear motor unit, ratchet, damper, and springs. Both, the rapid contraction and relaxation phases require a high order filter or alternatively a kernel filter, attributed to the nerve system as suggested by external electric stimulation. The respective response function is modelled by an electrical lumped circuit. Together with a reaction time and occasionally observed droops in the hold phase, both adjusted empirically, the monitored response is represented in close approximation by the combined electrical and mechanical lumped circuits. The respectively determined model parameters provide a refined evaluation scheme for the performance of monitored athletes. Valuable parameters relate to the latent period, the muscle response time, the activation and deactivation dynamics, a possible droop and other instabilities of the hold phase, and parameters characterizing the relaxation phase including the observed post tetanus overshoot and subsequent contraction. Monitored and modelled are also the different processes involved in active muscle dynamics including isotonic, isometric, and eccentric contraction or stretching. The developed technology provides time sequential observation of these processes and registration of their path in the extension and force parameter space. Under suitable conditions the closed-loop cycles of mind controlled human muscle movements proceed along characteristic lines coinciding with well identifiable elementary processes. The presentation of the monitored processes in the extension and force parameter space allows the determination of the mechanical energy expenditure for the observed different muscle actions. An elementary macroscopic mechanical model has been developed, suitable to express the basic features of the monitored muscle dynamics.:Table of Contents Chapter 1 1. Introduction 1 1.1 Monitoring of muscle biomechanics 1 1.2 Detection methods in biomechanics 2 1.3 Ultrasound in biomechanical application 5 1.4 Skeletal muscle 6 1.5 Activation of skeletal muscle 8 1.6 Catatonus effect 10 Chapter 2 2. Concepts and methods in ultrasonic motion monitoring 12 2.1 Ultrasound 12 2.2 Specific concepts of the developed ultrasonic detection scheme 16 2.2.1 Time-of-flight 17 2.2.2 Cross correlation 18 2.2.3 Concepts of cross correlation 19 2.2.4 Chirp technique 19 Chapter 3 3. Ultrasonic monitoring of the muscle extension 21 3.1 Data analysis 21 3.2 Application of the developed monitoring scheme 23 3.2.1 Fast signal and data acquisition mode 23 3.2.2 Monitoring with off-line evaluation 24 3.2.3 Method 26 3.2.4 Data evaluation 27 3.3 Quasi-continuous monitoring scheme 28 3.3.1 Slow with on-line data processing and display 29 3.3.2 Fast with data storage only 30 3.4 Monitoring with on-line evaluation 34 3.4.1 Application involving monitoring of athletic performance 36 3.4.2 Data evaluation 37 3.4.3 Summary 42 3.5 Comparative study of pre and post physical loading session 43 3.5.1 Method 43 3.5.2 Results 44 3.5.3 Summary 45 Chapter 4 4. High resolution monitoring of the velocity of ultrasound in contracting and relaxing muscle 47 4.1 Methods 49 4.2 Results and evaluation 51 4.2.1 Poission’s ratio for isometrically contracted muscle 52 4.3 Summary 53 Chapter 5 5. Monitoring of muscle dynamics, muscle force, and EMG 56 5.1 Synchronous monitoring of muscle dynamics with muscle force 56 5.1.1 Force-length dynamics under all-out isometric contraction 56 5.1.1.1 Method 56 5.1.1.2 Result and evaluation 58 5.1.2 Force-length dynamics of equal holding monitoring 62 5.1.2.1 Method 62 5.1.2.2 Results and evaluation 63 5.1.3 Summary 67 5.2 Synchronous monitoring of muscle movement with EMG 69 5.2.1 Method 69 5.2.2 Results and evaluation 70 5.3 Synchronous monitoring of muscle movement, EMG and muscle force 73 5.3.1 Method 73 5.3.2 Results and evaluation 74 5.3.3 Summary 77 Chapter 6 6. Monitoring of skeletal muscle dynamics under isometric contraction and modelling of the non-linear response including post tetanus effects 80 6.1 Method 82 6.2 Data analysis 82 6.3 Results and evaluation 82 6.3.1 Mechanical model 83 6.3.2 Equations relating to modelling 85 6.3.3 Comparison of experimental results and modelling 91 6.3.4 Electrical lumped circuit 93 6.4 Summary 100 Chapter 7 7. Lumped Circuit Model and Energy Transfer for quasi-static approximation 101 7.1 Basic muscle model and biomechanical processes 102 7.1.1 Muscle model 102 7.1.2 Force in the muscular motoric processes 104 7.2 Method 104 7.3 Results of experimental observations of muscle action 106 7.3.1 Muscle force and closed-loop contraction dynamics 106 7.3.2 Muscle work considerations 109 7.4 Summary 110 Chapter 8 8.1 Ultrasonic calliper 112 8.2 Interpretation of sound velocity variation in muscle 114 8.3 Monitored muscle dynamics 118 8.4 Isometric muscle action and tetanus effect 121 8.5 Quasi-static muscle action 125 8.6 Summarizing statement with a moderate outlook 126 References 128 Acknowledgements 140 Selbständigkeitserklärung 141

Experimental vibration analysis of mechanical structures is a well established field.Plenty of literature exists on macro scale structures in the fields of civil, mechanical and aerospace engineering, but the study of vibrations of micro scale structures such as MEMS, liquid droplets, and biological cells is relatively new. For such structures, the amplitudes of vibration are typically in nanometeror sub-nanometer range and the frequencies are in KHz to MHz range depending upon the dimensions of the structure. In our study, we use a scanningLaser Doppler Vibrometer (LDV) to measure the vibrations of micro-scale objects such as MEMS structures, micro droplets and cells. The vibrometercan capture frequency response up to 24 MHz withpicometer displacement resolution. First, we present the study of dynamics of a 2-D micromechanical structure—a MEMSelectrothermal actuator. The structure is realized using SOI MUMPs process from MEMSCAP. The fabricated device is tested for its dynamic performance characteristics using the LDV. In our experiments, we could capture up to 50 out-of-plane modes of vibration—an unprecedented capture—with a single excitation. Subsequent FEM based numerical simulations confirmed that the captured modes were indeed what the experiments indicated, and the measured frequencies werefound to be within 5% of theoretically predicted. Next, we study the dynamics of a 3-D micro droplet and show how the substrate adhesion modulates the natural frequency of the droplet. Adhesion properties of droplets are decided by the degree of wettability that is generally measured by the contact angle between the substrate and the droplet. In this work, we were able to capture 14 modes of vibration of a mercury droplet on different substrates and measure the correspondingfrequencies experimentally. We verify these frequencies with analytical calculations and find that all the measured frequencies are within 6% of theoretically predicted values. We also show that considering any two pairs of natural frequencies, we can calculate the surface tension and the contact angle, thus providing a new method for measuring adhesion of a droplet on an unknown surface. Lastly, we present a study of vibrations of biological cells.Our first study is that of single muscle fibers taken from drosophila.Muscle fibers with different pathological conditions were held in two structural configurations—asa fixed-fixed beam and a cantilever beam—and their vibration signatures analysed.We found that there was significant reduction in natural frequency of diseased fibers. Among the diseased fibers, we could confidently classify the myopathies into nemaline and cardiac types based on the natural frequency of single fibers. We have noticed that the elastic modulus of the muscle which decides the natural frequency is dictated by the myosin expression levels. Our last example isa study of the vibration signatures of cancer cells. Here we measure the natural frequencies of normal and certain cancerous cells, and show that we can distinguish the two based on their natural frequencies. We find that the natural frequency of cancerous cells is approximately half of that of normal cells. Within the cancerous cells, we are able to distinguished epithelial cancer cells and mesenchymal cancer cells based on their natural frequency values. For Epithelial cells,we activate the signaling pathways to induce EMT and notice the reduction in the natural frequency. This mechanical assay based on vibration response corroborates results from the biochemical assays such as Western blots and PCR, thus opening a new technique of mechano-diagnostics.