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Bragg Molography
Molography is a new optical biosensing technology that has been developed by a collaboration between Roche and our Group. In this project you will further develop the technology by building a new biosensor.
Label-free biosensors enable to monitor biomolecular interactions in real-time, which is key to assess the efficacy of drug candidates. In particular, optical biosensors – and more precisely – refractometric biosensor concepts such as SPR (Surface Plasmon Resonance) [1] are well-established to perform this task and extremely sensitive (1 pg/mm2). However, these approaches exhibit inherent drawbacks. Since they measure any change in refractive index on the surface they are susceptible to fluctuations in temperature, buffer composition and most importantly, any nonspecific binding to the sensor surface will generate a signal. These inherent problems bring experimental limitations, especially the inability to measure biochemical interactions in their biological environment (serum, plasma) or to assess interaction of low molecular weight analytes with target receptors. Diffractometric sensor technologies do not suffer these limitations, since their architecture is inherently self-referencing. Nevertheless, to date, these technologies were an order of magnitude less sensitive than refractometric approaches. [2,3] Recently, a diffractometric technology - Focal Molography - was introduced that is expected to be comparably sensitive like SPR and is real-time, label free and not restricted by non-specific binding. [4] Here we investigate another diffractometric biosensor concept that is based on Bragg reflection of a guided mode in a waveguide. Bragg reflection gratings on waveguide are a well established building block of integrated optics. [5] As in focal molography, the Bragg grating is built from the interacting molecules themselves. Bragg molography promises to generate a higher signal for the same amount of biological matter than focal molography. It’s disadvantage is, that the so-called Bragg condition must be fulfilled. This makes it extremely vulnerable to variations in the manufacturing process. In this project you will design a sensor, which will overcome this issue.
**References**:
[1] Homola, Jirí. 2008. “Surface Plasmon Resonance Sensors for Detection of Chemical and Biological Species.” Chemical Reviews 108
[2] Goh, Jane B., Pui L. Tam, Richard W. Loo, and M. Cynthia Goh. 2003. “A Quantitative Diffraction-Based Sandwich Immunoassay.” Analytical Biochemistry 313 (2): 262–66.
[3] Loo, Richard W., Pui L. Tam, Jane Betty Goh, and M. Cynthia Goh. 2005. “An Enzyme-Amplified Diffraction-Based Immunoassay.” Analytical Biochemistry 337 (2): 338–42.
[4] Fattinger, Christof. 2014. “Focal Molography: Coherent Microscopic Detection of Biomolecular Interaction.” Physical Review X 4 (3). American Physical Society: 031024
[5] Suhara, T., and H. Nishihara. 1986. “Integrated Optics Components and Devices Using Periodic Structures.” IEEE Journal of Quantum Electronics 22 (6): 845–67.
Label-free biosensors enable to monitor biomolecular interactions in real-time, which is key to assess the efficacy of drug candidates. In particular, optical biosensors – and more precisely – refractometric biosensor concepts such as SPR (Surface Plasmon Resonance) [1] are well-established to perform this task and extremely sensitive (1 pg/mm2). However, these approaches exhibit inherent drawbacks. Since they measure any change in refractive index on the surface they are susceptible to fluctuations in temperature, buffer composition and most importantly, any nonspecific binding to the sensor surface will generate a signal. These inherent problems bring experimental limitations, especially the inability to measure biochemical interactions in their biological environment (serum, plasma) or to assess interaction of low molecular weight analytes with target receptors. Diffractometric sensor technologies do not suffer these limitations, since their architecture is inherently self-referencing. Nevertheless, to date, these technologies were an order of magnitude less sensitive than refractometric approaches. [2,3] Recently, a diffractometric technology - Focal Molography - was introduced that is expected to be comparably sensitive like SPR and is real-time, label free and not restricted by non-specific binding. [4] Here we investigate another diffractometric biosensor concept that is based on Bragg reflection of a guided mode in a waveguide. Bragg reflection gratings on waveguide are a well established building block of integrated optics. [5] As in focal molography, the Bragg grating is built from the interacting molecules themselves. Bragg molography promises to generate a higher signal for the same amount of biological matter than focal molography. It’s disadvantage is, that the so-called Bragg condition must be fulfilled. This makes it extremely vulnerable to variations in the manufacturing process. In this project you will design a sensor, which will overcome this issue.
**References**: [1] Homola, Jirí. 2008. “Surface Plasmon Resonance Sensors for Detection of Chemical and Biological Species.” Chemical Reviews 108 [2] Goh, Jane B., Pui L. Tam, Richard W. Loo, and M. Cynthia Goh. 2003. “A Quantitative Diffraction-Based Sandwich Immunoassay.” Analytical Biochemistry 313 (2): 262–66. [3] Loo, Richard W., Pui L. Tam, Jane Betty Goh, and M. Cynthia Goh. 2005. “An Enzyme-Amplified Diffraction-Based Immunoassay.” Analytical Biochemistry 337 (2): 338–42. [4] Fattinger, Christof. 2014. “Focal Molography: Coherent Microscopic Detection of Biomolecular Interaction.” Physical Review X 4 (3). American Physical Society: 031024 [5] Suhara, T., and H. Nishihara. 1986. “Integrated Optics Components and Devices Using Periodic Structures.” IEEE Journal of Quantum Electronics 22 (6): 845–67.
**Theoretical:** Simulate the optical properties of the sensor using a commercial software and a python framework.
**Experimental:** Manufacturing of the sensor using micro-/nano fabrication technologies.
Build and adapt a readout set-up.
**Background and requirements:**
• High motivation • Above average grades • Optional: Knowledge in optics and photonics is a plus
If you are interested, please send me your transcript of records and CV.
**Theoretical:** Simulate the optical properties of the sensor using a commercial software and a python framework.
**Experimental:** Manufacturing of the sensor using micro-/nano fabrication technologies. Build and adapt a readout set-up.
**Background and requirements:** • High motivation • Above average grades • Optional: Knowledge in optics and photonics is a plus
If you are interested, please send me your transcript of records and CV.