INSCIT INVITED TALK: Andrew Taberner

Biomedical Instrumentation is designed to provide clinicians, scientists and consumers with useful information about the performance and properties of the human body in health and disease. In many applications in medicine and biology, scientific instruments and medical devices operate at the interface between the “soft” world of living organisms and biological substances and the “hard” world of measurement and actuation systems. The development of such instruments and devices requires the designer to draw from and master a wide range of techniques and tools that span biology, chemistry, materials science, optics, mechanics, mathematics, electronics, and computing.

Moreover, the characteristics of biological specimens can be very challenging to measure. Many of the properties of living organisms, and their tissues, are highly non-linear, and can vary throughout time and space. The measurement techniques required to quantify these properties usually span physical domains – electrical, chemical, mechanical, and optical – and may need to account for changes that occur temporally and spatially within the specimen under study. The complexity of the interactions between measured variables often demands that measurements be separated and interpreted with the aid of multi-scale computational models.

In this talk, I provide a brief example of the challenges and opportunities in bioinstrumentation and measurement, by overviewing the development of a unique scientific and medical instrument for studying heart muscle in health and disease.

The heart is a complex organic engine that converts chemical energy into work. Each heartbeat begins with an electrically-released pulse of calcium, which triggers force-development and cell shortening, at the cost of energy and oxygen, and the dissipation of heat. My group have developed new instrumentation systems to measure all of these processes simultaneously, while subjecting isolated samples of heart tissue to realistic contraction patterns that mimic the pressure-volume-time loops experienced by the heart with each beat. This demanding undertaking has required us to develop our own actuators, force transducers, heat sensors, and optical measurement systems. Our instruments make use of several different measurement modalities which are integrated in a robotic hardware-based real-time acquisition and control environment and interpreted with the aid of a computational model.

In this way, we can now resolve (to within a few nanoWatts) the heat released by living cardiac muscle fibers as they perform work at 37 °C. Muscle force and length are controlled and measured to microNewton and nanometer precision by a laser interferometer, while the muscle is scanned in the view of an optical microscope equipped with a fluorescent calcium imaging system. Concurrently, the changing muscle geometry is monitored in 4D by a custom-built optical coherence tomograph, and the spacing of muscle-proteins is imaged in real-time by transmission-microscopy and laser diffraction systems. Oxygen consumption is measured using fluorescence-quenching techniques.

Equipped with these unique capabilities, we have probed the mechano-energetics of failing hearts from rats with diabetes. We have found that the peak stress and peak mechanical efficiency of tissues from these hearts was normal, despite prolonged twitch duration. We have thus shown that the compromised mechanical performance of the diabetic heart arises from a reduced period of diastolic filling and does not reflect either diminished mechanical performance or diminished efficiency of its tissues. In another program of research, we have demonstrated that despite claims to the contrary, dietary supplementation by fish-oils has no effect on heart muscle efficiency. Neither of these insights were fully revealed until the development of this instrument.

In this talk I demonstrate that in the field of bioinstrumentation and measurement, there is a need for greater use of measurement techniques and experimental protocols that can allow researchers to gather functional multi-scale, multiphysics data from the same tissue or material source. In many cases, these data can be best interpreted holistically, with the aid of multi-physics sample-specific computational models.

Other measurement tools our lab has developed that also highlight the advantages of this approach include programmable multi-axis soft-tissue robots for measuring the mechanical/optical properties of skin, pericardium, the pelvic floor, and other biological tissues. We have also invented and developed a new class of devices for automated, controlled needle-free injection and extraction of fluids through skin and other biological tissues. These devices are being applied to monitoring change and managing disease in a range of human, animal and agricultural applications.