The feasibility of using hollow core photonic crystal fiber (HC-PCF) in conjunction with Raman spectroscopy has been explored for real time monitoring of heparin concentration in serum. Heparin is an important blood anti-coagulant whose precise monitoring and controlling in patients undergoing cardiac surgery and dialysis is of utmost importance. Our method of heparin monitoring offers a novel alternative to existing clinical procedures in terms of accuracy, response time and sample volume. The optical design configuration simply involves a 785-nm laser diode whose light is coupled into HC-PCF filled with heparin-serum mixtures. By non-selectively filling HC-PCF, a strong modal field overlap is obtained. Consequently, an enhanced Raman signal (>90 times) is obtained from various heparin-serum mixtures filled HC-PCFs compared to its bulk counterpart (cuvette). The present scheme has the potential to serve as a ‘generic biosensing tool’ for diagnosing a wide range of biological samples.

© 2011 OSA

1. S. A. Spinler, A. K. Wittkowsky, E. A. Nutescu, and M. A. Smythe, “Anticoagulation monitoring part 2: Unfractionated heparin and low-molecular-weight heparin,” Ann. Pharmacother. 39(7), 1275–1285 (2005). [CrossRef] [PubMed]
2. N. M. Milović, J. R. Behr, M. Godin, C. S. Hou, K. R. Payer, A. Chandrasekaran, P. R. Russo, R. Sasisekharan, and S. R. Manalis, “Monitoring of heparin and its low-molecular-weight analogs by silicon field effect,” Proc. Natl. Acad. Sci. U.S.A. 103(36), 13374–13379 (2006). [CrossRef] [PubMed]
3. Y. Nosé, “Hemodialysis patients’ deaths in the USA by contaminant suspected heparin originating from China,” Artif. Organs 32(6), 425–426 (2008). [CrossRef] [PubMed]
4. H. Szelke, J. Harenberg, and R. Krämer, “Detection and neutralisation of heparin by a fluorescent ruthenium compound,” Thromb. Haemost. 102(5), 859–864 (2009). [PubMed]
5. K. Gaus and E. A. H. Hall, “Evaluation of Surface Plasmon Resonance (SPR) for Heparin Assay,” J. Colloid Interface Sci. 194(2), 364–372 (1997). [CrossRef] [PubMed]
6. N. M. Milovic, J. R. Behr, M. Godin, C. S. Hou, K. R. Payer, A. Chandrasekaran, P. R. Russo, R. Sasisekharan, and S. R. Manalis, “Monitoring of heparin and its low-molecular-weight analogs by silicon field effect,” Proc. Natl. Acad. Sci. U.S.A. 103(36), 13374–13379 (2006). [CrossRef] [PubMed]
7. H. Yan, C. Gu, C. Yang, J. Liu, G. Jin, J. Zhang, L. Hou, and Y. Yao, “Hollow core photonic crystal fiber surface-enhanced Raman probe,” Appl. Phys. Lett. 89(20), 204101 (2006). [CrossRef]
8. J. B. Jensen, L. H. Pedersen, P. E. Hoiby, L. B. Nielsen, T. P. Hansen, J. R. Folkenberg, J. Riishede, D. Noordegraaf, K. Nielsen, A. Carlsen, and A. Bjarklev, “Photonic crystal fiber based evanescent-wave sensor for detection of biomolecules in aqueous solutions,” Opt. Lett. 29(17), 1974–1976 (2004). [CrossRef] [PubMed]
9. K. Nielsen, D. Noordegraaf, T. Sørensen, A. Bjarklev, and T. P. Hansen, “Selective filling of Photonic Crystal Fibres,” J. Opt. A, Pure Appl. Opt. 7(8), L13–L20 (2005). [CrossRef]
10. Y. Huang, Y. Xu, and A. Yariv, “Fabrication of functional microstructured optical fibers through a selective-filling technique,” Appl. Phys. Lett. 85(22), 5182–5184 (2004). [CrossRef]
11. M. Naji, A. Khetani, N. Lagali, R. Munger, and H. Anis, “A novel method of using hollow-core photonic crystal fiber as a Raman biosensor,” Proc. SPIE 6865, 68650E (2008). [CrossRef]
12. A. Khetani, M. Laferrière, H. Anis, and J. C. Scaiano, “Laser flash photolysis with nanoliter samples: photonic crystal fibers as ultrasmall smart test tubes,” J. Mater. Chem. 18(40), 4769–4774 (2008). [CrossRef]
13. V. S. Tiwari, A. Khetani, M. Naji, and H. Anis, “Study of Surface Enhanced Raman Scattering (SERS) within Hollow Core Photonic Crystal Fiber,” IEEE Sensors 5404, 367–370 (2009). [CrossRef]
14. A. Khetani, M. Naji, N. Lagali, R. Munger, and H. Anis, “A method for using Photonic Crystal Fiber as a Raman biosensor”, US Patent 2010/0014077 (2010).
15. G. Antonopoulos, F. Benabid, T. A. Birks, D. M. Bird, J. C. Knight, and P. St. J. Russell, “Experimental demonstration of the frequency shift of bandgaps in photonic crystal fibers due to refractive index scaling,” Opt. Express 14(7), 3000–3006 (2006). [CrossRef] [PubMed]
16. D. H. Atha, A. K. Gaigalas, and V. Reipa, “Structural analysis of heparin by raman spectroscopy,” J. Pharm. Sci. 85(1), 52–56 (1996). [CrossRef] [PubMed]
17. C. Herrmann, C. Vrancic, A. Fomichova, N. Gretz, S. Hoecker, A. Pucci, and W. Petrich, “In vitro characteristics of a mid-infrared continuous glucose sensor,” Proc. SPIE 7560, 75600E, 75600E-6 (2010). [CrossRef]

Ann. Pharmacother.

• S. A. Spinler, A. K. Wittkowsky, E. A. Nutescu, and M. A. Smythe, “Anticoagulation monitoring part 2: Unfractionated heparin and low-molecular-weight heparin,” Ann. Pharmacother. 39(7), 1275–1285 (2005). [CrossRef] [PubMed]

Appl. Phys. Lett.

• H. Yan, C. Gu, C. Yang, J. Liu, G. Jin, J. Zhang, L. Hou, and Y. Yao, “Hollow core photonic crystal fiber surface-enhanced Raman probe,” Appl. Phys. Lett. 89(20), 204101 (2006). [CrossRef]
• Y. Huang, Y. Xu, and A. Yariv, “Fabrication of functional microstructured optical fibers through a selective-filling technique,” Appl. Phys. Lett. 85(22), 5182–5184 (2004). [CrossRef]

Artif. Organs

• Y. Nosé, “Hemodialysis patients’ deaths in the USA by contaminant suspected heparin originating from China,” Artif. Organs 32(6), 425–426 (2008). [CrossRef] [PubMed]

IEEE Sensors

• V. S. Tiwari, A. Khetani, M. Naji, and H. Anis, “Study of Surface Enhanced Raman Scattering (SERS) within Hollow Core Photonic Crystal Fiber,” IEEE Sensors 5404, 367–370 (2009). [CrossRef]

J. Colloid Interface Sci.

• K. Gaus and E. A. H. Hall, “Evaluation of Surface Plasmon Resonance (SPR) for Heparin Assay,” J. Colloid Interface Sci. 194(2), 364–372 (1997). [CrossRef] [PubMed]

J. Mater. Chem.

• A. Khetani, M. Laferrière, H. Anis, and J. C. Scaiano, “Laser flash photolysis with nanoliter samples: photonic crystal fibers as ultrasmall smart test tubes,” J. Mater. Chem. 18(40), 4769–4774 (2008). [CrossRef]

J. Opt. A, Pure Appl. Opt.

• K. Nielsen, D. Noordegraaf, T. Sørensen, A. Bjarklev, and T. P. Hansen, “Selective filling of Photonic Crystal Fibres,” J. Opt. A, Pure Appl. Opt. 7(8), L13–L20 (2005). [CrossRef]

J. Pharm. Sci.

• D. H. Atha, A. K. Gaigalas, and V. Reipa, “Structural analysis of heparin by raman spectroscopy,” J. Pharm. Sci. 85(1), 52–56 (1996). [CrossRef] [PubMed]

Opt. Express

• G. Antonopoulos, F. Benabid, T. A. Birks, D. M. Bird, J. C. Knight, and P. St. J. Russell, “Experimental demonstration of the frequency shift of bandgaps in photonic crystal fibers due to refractive index scaling,” Opt. Express 14(7), 3000–3006 (2006). [CrossRef] [PubMed]

Opt. Lett.

• J. B. Jensen, L. H. Pedersen, P. E. Hoiby, L. B. Nielsen, T. P. Hansen, J. R. Folkenberg, J. Riishede, D. Noordegraaf, K. Nielsen, A. Carlsen, and A. Bjarklev, “Photonic crystal fiber based evanescent-wave sensor for detection of biomolecules in aqueous solutions,” Opt. Lett. 29(17), 1974–1976 (2004). [CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A.

• N. M. Milovic, J. R. Behr, M. Godin, C. S. Hou, K. R. Payer, A. Chandrasekaran, P. R. Russo, R. Sasisekharan, and S. R. Manalis, “Monitoring of heparin and its low-molecular-weight analogs by silicon field effect,” Proc. Natl. Acad. Sci. U.S.A. 103(36), 13374–13379 (2006). [CrossRef] [PubMed]
• N. M. Milović, J. R. Behr, M. Godin, C. S. Hou, K. R. Payer, A. Chandrasekaran, P. R. Russo, R. Sasisekharan, and S. R. Manalis, “Monitoring of heparin and its low-molecular-weight analogs by silicon field effect,” Proc. Natl. Acad. Sci. U.S.A. 103(36), 13374–13379 (2006). [CrossRef] [PubMed]

Proc. SPIE

• C. Herrmann, C. Vrancic, A. Fomichova, N. Gretz, S. Hoecker, A. Pucci, and W. Petrich, “In vitro characteristics of a mid-infrared continuous glucose sensor,” Proc. SPIE 7560, 75600E, 75600E-6 (2010). [CrossRef]
• M. Naji, A. Khetani, N. Lagali, R. Munger, and H. Anis, “A novel method of using hollow-core photonic crystal fiber as a Raman biosensor,” Proc. SPIE 6865, 68650E (2008). [CrossRef]

Thromb. Haemost.

• H. Szelke, J. Harenberg, and R. Krämer, “Detection and neutralisation of heparin by a fluorescent ruthenium compound,” Thromb. Haemost. 102(5), 859–864 (2009). [PubMed]

Other

• A. Khetani, M. Naji, N. Lagali, R. Munger, and H. Anis, “A method for using Photonic Crystal Fiber as a Raman biosensor”, US Patent 2010/0014077 (2010).

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