Optical techniques are widely used in clinical settings and biomedical research labs. These techniques include the study of fluorescence, bioluminescence, absorption, and scattering to determine changes in bio-molecular interactions. Optical techniques have been useful in exploring many phenomena in biological tissues, ranging from nm-scale molecular interactions to whole body studies in small animals and in vivo diagnostics in humans.
The ability to observe biological changes over many orders of magnitude in time and space has led many researchers to seek new techniques and uses for optical sensing and imaging in biomedicine.
The majority of optical bio-sensing and bio-imaging techniques use commercially-available lasers, detectors, lenses, spectrometers, and microscopes. Advances in microelectronics and optoelectronics fabrication techniques allow miniaturization of optical imaging and scanning systems and tailored light sources and detectors. Robust fabrication techniques in Silicon (Si) and Gallium Arsenide (GaAs) devices are increasingly used to create many semiconductor-based lasers, detectors, and waveguides optimized for biomedical applications.
Solutions for optical biomedical systems featuring two or more of the components integrated into a functional sub-unit enjoy several advantages over bulk optical systems. These include lower system costs as well as careful optimization of the components for increased sensitivity, speed, and functionality. Integrated imaging systems can offer new possibilities for fundamental studies and future bio-medical and bio-defense applications. For example, the tremendous reduction in size, power, and cost of an integrated system enables long term investigations on freely-behaving, unanesthetized animals that are impossible with existing technologies. Likewise, combining several sensors within a lab-on-a-chip portable diagnostic system allows for parallel analysis of several blood chemistry components. In many instances, the smaller size of integrated optical measurement systems facilitates inspection of small body cavities (through endoscopy) and improved portability. While improved portability is desired f or such optical systems to be used for human diagnostics and therapy, it is essential for long-term monitoring and animal studies.
We present novel optical techniques based on a fully-integrated sensor as a building block for bio-sensing and bio-imaging. Key enabling technologies for these techniques are micro-fluidics, miniature optics, VCSELs, Si and GaAs-based detectors, and CMOS circuits that can be integrated together to perform optimized bio-sensing, bio-imaging, and bio-molecular dynamics studies. An example of the fully-integrated sensor module is shown in Figure 1, where a VCSEL and GaAs detector are monolithically integrated. We utilize a high-NA micro-lens to focus laser emission into the tissue or flow channel and collect the returning (scattered, reflected, or fluorescence) light into the detector (Figure 1(a)). Figure 1(b) shows a Scanning Electron Microscope (SEM) image of a monolithically integrated source and detector. We can design the sensor to operate at a desired wavelength within the near-infrared (near-IR) to provide low tissue absorption and low bio-molecular autofluorescence. Consequently, we can achieve deep tissue penetration and low background emission levels for improved sensitivity.