ABSTRACT
Biosensors are essential for biomedical diagnostics and to perform fundamental investigations in biology and life sciences. Of many different approaches to biosensing, optical methods are highly desirable because they provide noninvasive remote and possibly multiplexed measurements over a wide eld of view that can resolve fast processes underlying their optical responses (e.g., kinetics of biochemical interaction). Optical methods are primarily based on luminescence, which is a result of photoemission such as phosphorescence, uorescence, bioluminescence, or chemiluminescence from an optical marker attached to the desired target, or it is due to intrinsic material response to light from scattering, absorption, change in polarization, nonlinear interaction, or heating. Some well-known examples of optical biosensors include imaging of pathogens (viruses and bacteria) in cell cultures, infrared (IR) in vivo imaging of tissues for tumor identication, metabolic assay for imaging glucose, oxygen consumption in cells and tissues, and high-throughput DNA and genome sequencing and protein detection. However, many traditional optical biosensors require extensive sample extraction and preparation that consumes lots
7.1 Introduction .................................................................................................. 141 7.2 CMOS Photodetectors for Optical Biosensing ............................................. 142
7.2.1 Linear-Mode P-N Junction Photodetectors ...................................... 143 7.2.2 Avalanche Photodiodes ..................................................................... 147
7.3 Applications .................................................................................................. 150 7.3.1 CMOS Imagers for Luminescence Spectroscopy ............................. 150
7.3.1.1 Intensity-Based Luminescence Imaging ............................ 150 7.3.1.2 Time-Resolved Luminescence Spectroscopy .................... 153
7.3.2 Integrated CMOS Image Sensors for Spectroscopy ......................... 160 7.3.3 Biosensors with Commercial Off-the-Shelf CMOS Camera ........... 162
7.3.3.1 Lensless Ultrawide-Field-of-View Cell Monitoring .......... 162 7.4 Summary ...................................................................................................... 164 References .............................................................................................................. 164
of reagents and also requires large amount of input sample for reliable measurements. Instrumentation for such biosensors is largely based on discrete optical and electronic components such as CCD cameras, photomultiplier tubes (PMTs), lenses, objectives, beam splitters, and readout ampliers that result in large benchtop instruments. While sophisticated optical instrumentation may be required for extreme measurements (nanometer spatial resolution or femtosecond time resolution), they are, however, very expensive and bulky for routine biological investigations and medical diagnostics. Miniaturization and cost reduction of optical biosensors are therefore essential. Mainstream complementary metal-oxide semiconductor (CMOS) technology provides an ideal platform for low-cost, portable imaging platforms for biosensing.
