The document discusses the significance of glucose measurement for diabetes management and introduces surface-enhanced Raman spectroscopy (SERS) as a method for enhancing the detection of glucose. It highlights the advantages of SERS over traditional Raman spectroscopy and reviews studies that demonstrate its application for glucose sensing, including both in vitro and in vivo approaches. Limitations and future development steps for improving SERS technology are also addressed.

1. 1
Measurement of Glucose by
Surface Enhanced Raman Spectroscopy
Nuzhet Nihaar Nasir Ahamed

2. TOPICS TO BE COVERED
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3. Why is measuring glucose important?
• To understand effect of food in blood
• To manage diabetes
• To help diabetic patients know their glycemic levels
• To ensure safe delivery for pregnant diabetic women
Glucose measurement  helps to control diabetes
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4. Surface Enhanced Raman Spectroscopy
• Principle  Raman Scattering
• Raman Spectrum  obtained by directing single wavelength of light and collecting the resulting
scattered light.
Modern Raman Spectroscopy – A Practical Approach W.E. Smith and G. Dent 2005 John Wiley & Sons, Ltd ISBNs: 0-471-49668-5 (HB); 0-471-49794-0 (PB)
Vibrational and Rotational
frequencies of a molecule are
characteristic of the molecule
 Helps to identify the molecules
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5. Surface Enhanced Raman Spectroscopy
SERS increases intensity of Raman signal when target analyte
molecules are adsorbed on the nanostructured metal substrate. 5

6. Surface Enhanced Raman Spectroscopy
Why SERS?
• To overcome disadvantages of Raman Spectroscopy
o Underdeveloped technique
o Sample degradation
• Enormous increase in intensities of Raman signals
• Measures adsorption of molecules on nanostructures
Mechanisms of intensity enhancement
• Electromagnetic enhancement
- Incident light  creates localized surface plasmons  plasmon oscillates  scattering increases
with perpendicular oscillations
• Chemical enhancement
- Incident light  Chemisorption of the surface  Charge transfer  Increases scattering
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7. Surface Enhanced Raman Spectroscopy
Instrumentation
Components
• monochromatic laser light source
• band-pass filter
• series of steering, focusing optics
• collection optics
• spectrometer
• CCD detector
Stuart, A Douglas; Walsh, T Joseph; Duyne, Van,P Richard; Dept of Chemistry and Biomed Engg, Anal. Chem. 2006, 78, 7211-7215.
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8. Review of article 1
Glucose Sensing Using Near-Infrared Surface-Enhanced Raman Spectroscopy:
Gold Surfaces, 10-Day Stability, and Improved Accuracy
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9. Review of article 1
Sample Preparation
Schematic of sensing surface.
Preparation of Ag/Au SAM Partitioning and de-partitioning of the SAM by glucose
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Stuart, A Douglas; Zhang, Xiaoyu, Lyandres, Olga; T Joseph; Duyne, Van,P Richard; Dept of Chemistry and Biomed Engg, Anal. Chem. 2005, 77, 4013-4019.

10. Review of article 1
Reflectance spectroscopy
λex = 750nm
λmin for the AgFON = 738nm
λmin for the AuFON = 778nm
AuFON is therefore better tuned to higher λex
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Stuart, A Douglas; Zhang, Xiaoyu, Lyandres, Olga; T Joseph; Duyne, Van,P Richard; Dept of Chemistry and Biomed Engg, Anal. Chem. 2005, 77, 4013-4019.

11. Review of article 1
Electrochemical measurements
CV for days 1 (black), 5
(red), and 10 (blue) on
the Ag electrode
CV for days 1 (black), 6
(red), and 10 (blue) on
the Au electrode
Percentages of
current maximum vary
with time
SAMs are more stable and better ordered on gold than silver surfaces
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Stuart, A Douglas; Zhang, Xiaoyu, Lyandres, Olga; T Joseph; Duyne, Van,P Richard; Dept of Chemistry and Biomed Engg, Anal. Chem. 2005, 77, 4013-4019.

12. Review of article 1
SERS spectroscopy
SERS Spectra
Time course of the intensity to the
∼699-cm-1 peak
AgFON AuFON
AgFONs rapidly lost signal
AuFONs remained stable for 10 days
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Stuart, A Douglas; Zhang, Xiaoyu, Lyandres, Olga; T Joseph; Duyne, Van,P Richard; Dept of Chemistry and Biomed Engg, Anal. Chem. 2005, 77, 4013-4019.

13. Review of article 1
Clarke error grid
• Compare the accuracy and performance of glucose sensors in the clinically relevant range
• Divided into 5 regions
(A)clinically correct measurement and treatment
(B) benign errors or no treatment
(C) incorrect measurements leading to overcorrection of acceptable glucose levels
(D)dangerous failure to detect and treat
(E) treatments that further aggravate abnormal glucose levels
Calibration plot Validation plot
94% of the data points in the
calibration plot and 91% of data
points in the prediction plot fall
within the acceptable region.
Stuart, A Douglas; Zhang, Xiaoyu, Lyandres, Olga; T Joseph; Duyne, Van,P Richard; Dept of Chemistry and Biomed Engg, Anal. Chem. 2005, 77, 4013-4019.
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14. Review of article 1
Conclusion
• AuFONs exhibit surface plasmon resonances at longer
wavelengths than similar AgFONs
• SAM is more stable on the gold surface by both cyclic voltammetry
and SERS spectroscopy
• AuFON sensor is capable of making acceptably accurate
concentration measurements even when challenged with a diverse
sample population
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15. Review of article 2
Transcutaneous Glucose Sensing by Surface-Enhanced Spatially Offset Raman
Spectroscopy (SESORS) in a Rat Model
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16. Review of article 2
Sample Preparation
Preparation of Ag Self Assembled Monolayer
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Yuen, M Jonathan; Shah, C Nilam; Glucksberg, R Mathew; Walsh, T Joseph; Duyne, Van,P Richard; Dept of Chemistry and Biomed Engg, Anal. Chem. 2010, 82, 8382–8385

17. Review of article 2
Spectroscopic Measurement
SERS spectra
SESORS spectra
• SERS signal is attenuated by approximately 95% due to presence of skin
• But, all spectral features were easily observed with high signal to noise ratio
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Yuen, M Jonathan; Shah, C Nilam; Glucksberg, R Mathew; Walsh, T Joseph; Duyne, Van,P Richard; Dept of Chemistry and Biomed Engg, Anal. Chem. 2010, 82, 8382–8385

18. Review of article 2
Clarke error grid
• 7 of the 9 validation points fell within the A and B ranges
• Few deviations were observed but it was improved by increasing the number of data
points in the calibration
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Yuen, M Jonathan; Shah, C Nilam; Glucksberg, R Mathew; Walsh, T Joseph; Duyne, Van,P Richard; Dept of Chemistry and Biomed Engg, Anal. Chem. 2010, 82, 8382–8385

19. Review of article 2
Conclusion
Despite the numerical disparity, SERS sensor is viable in vivo and can detect glucose
concentration fluctuations over time.
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Yuen, M Jonathan; Shah, C Nilam; Glucksberg, R Mathew; Walsh, T Joseph; Duyne, Van,P Richard; Dept of Chemistry and Biomed Engg, Anal. Chem. 2010, 82, 8382–8385

20. Limitations of SERS
• Large refractive index change between skin and air immediately produces intensity losses due to back
reflections
• Light is further attenuated due to multiple scattering and absorption within skin layers.
• Placement of the SERS-active surface in vivo
• The natural inflammation and foreign body response (FBR) from the human body
Future Developmental Steps
• Developing next generation substrates to obtain SERS signal amplification by 100 times
• New surface modification strategies to improve reproducibility of SERS sensor chip
• Explore modified field surfaces to expand the number of biological targets accessible to SERS
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21. Questions?
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22. Thank you
for
your kind attention
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