ECE 416

• Biomedical Imaging, Bioengineering, and Acoustics

Grading: Five homework assignments (40% of grade), fourteen online mini-exams (30% of grade) and one term paper project (30% of grade). For the term paper, each student develops a new biosensor-related idea in the format of a National Science Foundation research proposal that incorporates an abstract, literature review, background/significance, preliminary data, and approach.

• Introduction to the field of biosensors, applications, and the use of
  statistical information to analyze biosensor ourput
• The design and capabilities of bioselective layers
• Biomolecular structure and function
• Mass transport and biosensing in a flow stream
• Biosensor figures of merit for comparison of approaches
• Homogeneous and heterogeneous assays: fluorescence polarization
• Electrochemical biosensors
• Acoustic biosensors
• Optical biosensors
• Fluorescence, Raman Spectroscopy, and Fluorescence Enhancement,
  and DNA microarrays
• Nanoparticle and microparticle labels
• Next-generation DNA sequencing technology
• Mobile/Point of Care biosensors
• Faculty guest lectures on biosensor applications in research

• Introduction to the field of biosensors including their role in medical care, biology research, defense, and society.
• Applications of biosensors that demonstrate their broad applicability and range of size, cost, and complexity that allow them to meet specific requirements.
• Biosensor statistics describe the most commonly used mathematical and graphical representation tools to analyze biosensor output, and how biosensor reproducibility and various sources of noise can compromise a biosensor’s ability to observe a signal or to differentiate between two analyte concentrations.
• Surface chemistry describes the approaches used to make covalent attachment of molecules like antibodies or DNA to biosensor surfaces, which enable the sensor to selectively recognize a specific target molecule within a complex test sample, such as blood.
• Biomolecular structure and function describes the building blocks of DNA and protein molecules, and the relevant features of those molecules that allow them to be attached to a biosensor surface, and to subsequently recognize its target.
• Mass transport describes the process by which molecules diffuse to and interact with a biosensor surface by chemical equilibrium interactions, and how a biosensor signal is generated kinetically as a function of time. We describe situations in which either mass transport flow or chemical reaction rates can limit the rate of molecule detection, and the difference between biosensor binding curves generated by each limitation. The design of microfluidic channel interfaces with biosensors and the selection of flow rates is discussed.
• Biosensor figures of merit describe the performance metrics by which sensor technologies that operate by different mechanisms can be compared to each other, enabling the relative strengths and weaknesses of detection approaches to be compared by their sensitivity, throughput, dynamic range, limit of detection, and limit of quantitation.
• Next generation DNA sequencing describes the fluorescence-based detection, data processing methods, and biochemistry methods used predominantly for genome sequencing in the technology offered by Illimina, as well as alternative approaches that may offer advantages in terms of throughput, cost, accuracy, and read length.
• Electrochemical biosensors explores the development of three successively developed generations of blood glucose sensors, starting with the Clark oxygen electrode, and extending to the solid electrodes used most commonly for monitoring blood glucose levels. The role of electron transfer mediators, enzymes, semipermeable membranes, and redox reactions in the generation of a voltage output that is proportional to glucose concentration are discussed.
• Acoustic biosensors describes the quartz crystal microbalance, Love-wave membrane resonators, and shear wave resonators that can directly detect biomolecule, viral, or bacterial attachment. Commercial products based upon acoustic sensor technology is described.
• Optical biosensors include sensors based upon surface plasmon resonance and photonic crystal resonance to detect biomaterial using its intrinsic dielectric permittivity. We discuss fundamentally why biomaterial has a greater dielectric permittivity than water, and how this can be used to devise sensor surfaces and detection instruments to precisely measure the interaction of biomaterial with light, including the use of waveguides and evanescent electromagnetic fields.
• Fluorescence is described from its quantum mechanical origins, including Jablonski energy band diagrams, the Stokes shift, fluorescence lifetime, and quantum efficiency. Several representative fluorescent dye molecules are described, and their features that underlie their ability to interact with external applied illumination with polarization dependence. Fluorescence detection instrumentation design, including confocal laser scanners and fluorescence microscopes are described, including the selection of light sources, filters, and photon detectors.
• Raman Spectroscopy and Surface Enhanced Raman Spectroscopy are taught beginning with the fundamental principles of photon scattering, and excitation of mechanical vibrations in molecules. Stokes, Anti-Stokes, and IR absorption are differentiated from each other, and the relationship between electric field and Raman intensity is described. Raman instrumentation and SERS surfaces are described, including selection of laser wavelength, design of SERS surfaces for maximization of electromagnetic hot spots, and the effects of autofluorescence.
• Quantum dots are described as a representative nanoparticle tag that can be used in place of fluorescent dyes for some applications. QD physics is briefly described, along with fabrication methods, selection of materials, and the effects of QD diameter on emission wavelength. QD-related phenomena such as blinking and photobleaching are discussed, along with QD applications in cell microscopy.
• Smartphone biosensors are described that enable point-of-care and point-of-use applications for biosensors that utilize the image sensors, communications, and computational capability of mobile devices.
• Photonic crystal biosensor microscopy describes how optical metamaterial surfaces can be used in the context of microscopy imaging to amplify the contrast for detection of biological analytes through enhanced absorption, enhanced fluorescence, and enhanced scattering with resulting capabilities for sensing molecules, viruses, and extracellular vesicles with single-unit precision.

Knowlege at the level of undergraduate physics on topics that inclulde polarization, wave propagation, refractive index, wavelength, frequency, refraction, and diffraction.

No textbook. Reading assignments are drawn from scientific literature.

• To teach the fundamental concepts behind the operation of the most important classes of biosensors (1)
• To teach how biosensors are characterized, compared to each other, and designed to suit particular applications (2)
• To teach how biochemical functionality is coupled to a biosensor transducer (6)
• To describe the major applications of biosensor technology in diagnostic tests, life science research, and environmental testing (7)
• To expose students to several of the most important emerging biosensor technologies (7)
• To encourage the practice of critical thinking when considering a new detection technology and to develop the ability to communicate well-researched opinions to others (3,4)