Abstract

Optical rotation (OR) polarimeters measure only the OR of a linearly polarized wave vector caused by the optical activity of the measured material. Such polarimeters are used to detect optically active materials and measure their concentration. Here we describe a novel type of high-resolution OR polarimeter. The new polarimeter is a compact device, based on a combination of two novel mechanisms: a referencing mechanism and an optical signal-gain mechanism. The patented referencing mechanism allows accurate measurements of small ORs in the presence of considerable polarization noise. The current limit of detection of the polarimeter is 20 micro-degrees, which we believe can be lowered further. The polarimeter is intended to serve as an add-on detector for existing high-pressure liquid chromatography (HPLC) systems in the pharmaceutical industry. The need for such a polarimeter, its optical setup, analysis of its performance, and experimental results are hereby given and discussed.

© 2014 Optical Society of America

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  1. W. Rehman, L. M. Arfons, and H. M. Lazarus, “The rise, fall and subsequent triumph of thalidomide: lessons learned in drug development,” Ther. Adv. Hematol. 2, 291–308 (2011).
    [CrossRef]
  2. W. H. De Camp, “The FDA perspective on the development of stereoisomers,” Chirality 1, 2–6 (1989).
    [CrossRef]
  3. FDA, “FDA’s policy statement for the development of new stereoisomeric drugs,” Chirality 4, 338–340 (1992).
    [CrossRef]
  4. S. W. Smith, “Chiral toxicology: it’s the same thing…only different,” Toxicol. Sci. 110, 4–30 (2009).
    [CrossRef]
  5. A. De Palma, “Drug development through the looking glass,” in PharmaManufacturing.com (PharmaManufacturing, 2006).
  6. D. J. Bornhop and S. Dotson, “Micro-scale polarimetry,” in Chiral Analysis, K. W. Busch and M. A. Busch, eds. (Elsevier, 2006), pp. 343–360.
  7. K. W. Busch, M. A. Busch, and C. Calleja-Amador, “Instrumental aspects of chiroptical detection,” in Chiral Analysis, K. W. Busch and M. A. Busch, eds. (Elsevier, 2006), pp. 299–341.
  8. S. Lan and E. Samad, “Low-birefringence lens design for polarization sensitive optical systems,” in Geometrical Optics and Lens Design, M. S. Jose and G. T. Mary, eds. (SPIE, 2006), p. 62890H.
  9. M. Sakhnovskii and B. Timochko, “Compensation for phase and amplitude distortions introduced by a quarter-wave plate in stokes-polarimetric measurements with magneto-optical modulation,” J. Appl. Spectrosc. 65, 844–847 (1998).
    [CrossRef]
  10. E. J. Gillham, “A high-precision photoelectric polarimeter,” J. Sci. Instrum. 34, 435–439 (1957).
    [CrossRef]
  11. E. S. Yeung, L. E. Steenhoek, S. D. Woodruff, and J. C. Kuo, “Detector based on optical activity for high performance liquid chromatographic detection of trace organics,” Anal. Chem. 52, 1399–1402 (1980).
    [CrossRef]
  12. Y. Zhang, D. R. Wu, D. B. Wang-Iverson, and A. A. Tymiak, “Enantioselective chromatography in drug discovery,” Drug Discov. Today 10(8), 571–577 (2005).
    [CrossRef]
  13. J. C. Giddings, “Part I principles and theory,” in Dynamics of Chromatography, J. C. Giddings and R. H. Knox, eds. (Marcel Dekker, 1965).
  14. L. Kott, W. B. Holzheuer, M. M. Wong, and G. K. Webster, “An evaluation of four commercial HPLC chiral detectors: a comparison of three polarimeters and a circular dichroism detector,” J. Pharm. Biomed. Anal. 43, 57–65 (2007).
    [CrossRef]
  15. R. Däppen, P. Voigt, F. Maystre, and A. E. Bruno, “Aspects of quantitative determinations with polarimetric detectors in liquid chromatography,” Anal. Chim. Acta 282, 47–54 (1993).
    [CrossRef]
  16. F. G. Sanchez, A. N. Diaz, and I. M. Lama, “Polarimetric detection in liquid chromatography: an approach to correct refractive index artefacts,” J. Liq. Chromatogr. Relat. Technol. 31, 3115–3131 (2008).
    [CrossRef]
  17. H.-J. King, C. Chou, H. Chang, and Y.-C. Huang, “Concentration measurements in chiral media using optical heterodyne polarimeter,” Opt. Commun. 110, 259–262 (1994).
    [CrossRef]
  18. T. Mitsui and K. Sakurai, “Precise measurement of the refractive index and optical rotatory power of a suspension by a delayed optical heterodyne technique,” Appl. Opt. 35, 2253–2258 (1996).
    [CrossRef]
  19. T. Mitsui and K. Sakurai, “Microdegree azimuth polarimeter using optical heterodyne detection,” Jpn. J. Appl. Phys. 35, 4844–4847 (1996).
    [CrossRef]
  20. C. Chou, “A phase sensitive optical rotation measurement in a scattered chiral medium using a Zeeman laser,” Opt. Commun. 230, 259–266 (2004).
    [CrossRef]
  21. J.-F. Lin, C.-C. Chang, C.-D. Syu, Y.-L. Lo, and S.-Y. Lee, “A new electro-optic modulated circular heterodyne interferometer for measuring the rotation angle in a chiral medium,” Opt. Lasers Eng. 47, 39–44 (2009).
    [CrossRef]
  22. C. Chou, K.-H. Chiang, K.-Y. Liao, Y.-F. Chang, and C.-E. Lin, “Polarized photon-pairs heterodyne polarimetry for ultrasensitive optical activity detection of a chiral medium,” J. Phys. Chem. B 111, 9919–9922 (2007).
    [CrossRef]
  23. J.-Y. Lee and D.-C. Su, “Improved common-path optical heterodyne interferometer for measuring small optical rotation angle of chiral medium,” Opt. Commun. 256, 337–341 (2005).
    [CrossRef]
  24. D. Goldberg and Z. Weissman, “Heterodyne polarimeter with a background subtraction system,” Application No. 20110176132 (2009).

2011 (1)

W. Rehman, L. M. Arfons, and H. M. Lazarus, “The rise, fall and subsequent triumph of thalidomide: lessons learned in drug development,” Ther. Adv. Hematol. 2, 291–308 (2011).
[CrossRef]

2009 (2)

S. W. Smith, “Chiral toxicology: it’s the same thing…only different,” Toxicol. Sci. 110, 4–30 (2009).
[CrossRef]

J.-F. Lin, C.-C. Chang, C.-D. Syu, Y.-L. Lo, and S.-Y. Lee, “A new electro-optic modulated circular heterodyne interferometer for measuring the rotation angle in a chiral medium,” Opt. Lasers Eng. 47, 39–44 (2009).
[CrossRef]

2008 (1)

F. G. Sanchez, A. N. Diaz, and I. M. Lama, “Polarimetric detection in liquid chromatography: an approach to correct refractive index artefacts,” J. Liq. Chromatogr. Relat. Technol. 31, 3115–3131 (2008).
[CrossRef]

2007 (2)

C. Chou, K.-H. Chiang, K.-Y. Liao, Y.-F. Chang, and C.-E. Lin, “Polarized photon-pairs heterodyne polarimetry for ultrasensitive optical activity detection of a chiral medium,” J. Phys. Chem. B 111, 9919–9922 (2007).
[CrossRef]

L. Kott, W. B. Holzheuer, M. M. Wong, and G. K. Webster, “An evaluation of four commercial HPLC chiral detectors: a comparison of three polarimeters and a circular dichroism detector,” J. Pharm. Biomed. Anal. 43, 57–65 (2007).
[CrossRef]

2005 (2)

J.-Y. Lee and D.-C. Su, “Improved common-path optical heterodyne interferometer for measuring small optical rotation angle of chiral medium,” Opt. Commun. 256, 337–341 (2005).
[CrossRef]

Y. Zhang, D. R. Wu, D. B. Wang-Iverson, and A. A. Tymiak, “Enantioselective chromatography in drug discovery,” Drug Discov. Today 10(8), 571–577 (2005).
[CrossRef]

2004 (1)

C. Chou, “A phase sensitive optical rotation measurement in a scattered chiral medium using a Zeeman laser,” Opt. Commun. 230, 259–266 (2004).
[CrossRef]

1998 (1)

M. Sakhnovskii and B. Timochko, “Compensation for phase and amplitude distortions introduced by a quarter-wave plate in stokes-polarimetric measurements with magneto-optical modulation,” J. Appl. Spectrosc. 65, 844–847 (1998).
[CrossRef]

1996 (2)

T. Mitsui and K. Sakurai, “Microdegree azimuth polarimeter using optical heterodyne detection,” Jpn. J. Appl. Phys. 35, 4844–4847 (1996).
[CrossRef]

T. Mitsui and K. Sakurai, “Precise measurement of the refractive index and optical rotatory power of a suspension by a delayed optical heterodyne technique,” Appl. Opt. 35, 2253–2258 (1996).
[CrossRef]

1994 (1)

H.-J. King, C. Chou, H. Chang, and Y.-C. Huang, “Concentration measurements in chiral media using optical heterodyne polarimeter,” Opt. Commun. 110, 259–262 (1994).
[CrossRef]

1993 (1)

R. Däppen, P. Voigt, F. Maystre, and A. E. Bruno, “Aspects of quantitative determinations with polarimetric detectors in liquid chromatography,” Anal. Chim. Acta 282, 47–54 (1993).
[CrossRef]

1992 (1)

FDA, “FDA’s policy statement for the development of new stereoisomeric drugs,” Chirality 4, 338–340 (1992).
[CrossRef]

1989 (1)

W. H. De Camp, “The FDA perspective on the development of stereoisomers,” Chirality 1, 2–6 (1989).
[CrossRef]

1980 (1)

E. S. Yeung, L. E. Steenhoek, S. D. Woodruff, and J. C. Kuo, “Detector based on optical activity for high performance liquid chromatographic detection of trace organics,” Anal. Chem. 52, 1399–1402 (1980).
[CrossRef]

1957 (1)

E. J. Gillham, “A high-precision photoelectric polarimeter,” J. Sci. Instrum. 34, 435–439 (1957).
[CrossRef]

Arfons, L. M.

W. Rehman, L. M. Arfons, and H. M. Lazarus, “The rise, fall and subsequent triumph of thalidomide: lessons learned in drug development,” Ther. Adv. Hematol. 2, 291–308 (2011).
[CrossRef]

Bornhop, D. J.

D. J. Bornhop and S. Dotson, “Micro-scale polarimetry,” in Chiral Analysis, K. W. Busch and M. A. Busch, eds. (Elsevier, 2006), pp. 343–360.

Bruno, A. E.

R. Däppen, P. Voigt, F. Maystre, and A. E. Bruno, “Aspects of quantitative determinations with polarimetric detectors in liquid chromatography,” Anal. Chim. Acta 282, 47–54 (1993).
[CrossRef]

Busch, K. W.

K. W. Busch, M. A. Busch, and C. Calleja-Amador, “Instrumental aspects of chiroptical detection,” in Chiral Analysis, K. W. Busch and M. A. Busch, eds. (Elsevier, 2006), pp. 299–341.

Busch, M. A.

K. W. Busch, M. A. Busch, and C. Calleja-Amador, “Instrumental aspects of chiroptical detection,” in Chiral Analysis, K. W. Busch and M. A. Busch, eds. (Elsevier, 2006), pp. 299–341.

Calleja-Amador, C.

K. W. Busch, M. A. Busch, and C. Calleja-Amador, “Instrumental aspects of chiroptical detection,” in Chiral Analysis, K. W. Busch and M. A. Busch, eds. (Elsevier, 2006), pp. 299–341.

Chang, C.-C.

J.-F. Lin, C.-C. Chang, C.-D. Syu, Y.-L. Lo, and S.-Y. Lee, “A new electro-optic modulated circular heterodyne interferometer for measuring the rotation angle in a chiral medium,” Opt. Lasers Eng. 47, 39–44 (2009).
[CrossRef]

Chang, H.

H.-J. King, C. Chou, H. Chang, and Y.-C. Huang, “Concentration measurements in chiral media using optical heterodyne polarimeter,” Opt. Commun. 110, 259–262 (1994).
[CrossRef]

Chang, Y.-F.

C. Chou, K.-H. Chiang, K.-Y. Liao, Y.-F. Chang, and C.-E. Lin, “Polarized photon-pairs heterodyne polarimetry for ultrasensitive optical activity detection of a chiral medium,” J. Phys. Chem. B 111, 9919–9922 (2007).
[CrossRef]

Chiang, K.-H.

C. Chou, K.-H. Chiang, K.-Y. Liao, Y.-F. Chang, and C.-E. Lin, “Polarized photon-pairs heterodyne polarimetry for ultrasensitive optical activity detection of a chiral medium,” J. Phys. Chem. B 111, 9919–9922 (2007).
[CrossRef]

Chou, C.

C. Chou, K.-H. Chiang, K.-Y. Liao, Y.-F. Chang, and C.-E. Lin, “Polarized photon-pairs heterodyne polarimetry for ultrasensitive optical activity detection of a chiral medium,” J. Phys. Chem. B 111, 9919–9922 (2007).
[CrossRef]

C. Chou, “A phase sensitive optical rotation measurement in a scattered chiral medium using a Zeeman laser,” Opt. Commun. 230, 259–266 (2004).
[CrossRef]

H.-J. King, C. Chou, H. Chang, and Y.-C. Huang, “Concentration measurements in chiral media using optical heterodyne polarimeter,” Opt. Commun. 110, 259–262 (1994).
[CrossRef]

Däppen, R.

R. Däppen, P. Voigt, F. Maystre, and A. E. Bruno, “Aspects of quantitative determinations with polarimetric detectors in liquid chromatography,” Anal. Chim. Acta 282, 47–54 (1993).
[CrossRef]

De Camp, W. H.

W. H. De Camp, “The FDA perspective on the development of stereoisomers,” Chirality 1, 2–6 (1989).
[CrossRef]

De Palma, A.

A. De Palma, “Drug development through the looking glass,” in PharmaManufacturing.com (PharmaManufacturing, 2006).

Diaz, A. N.

F. G. Sanchez, A. N. Diaz, and I. M. Lama, “Polarimetric detection in liquid chromatography: an approach to correct refractive index artefacts,” J. Liq. Chromatogr. Relat. Technol. 31, 3115–3131 (2008).
[CrossRef]

Dotson, S.

D. J. Bornhop and S. Dotson, “Micro-scale polarimetry,” in Chiral Analysis, K. W. Busch and M. A. Busch, eds. (Elsevier, 2006), pp. 343–360.

Giddings, J. C.

J. C. Giddings, “Part I principles and theory,” in Dynamics of Chromatography, J. C. Giddings and R. H. Knox, eds. (Marcel Dekker, 1965).

Gillham, E. J.

E. J. Gillham, “A high-precision photoelectric polarimeter,” J. Sci. Instrum. 34, 435–439 (1957).
[CrossRef]

Goldberg, D.

D. Goldberg and Z. Weissman, “Heterodyne polarimeter with a background subtraction system,” Application No. 20110176132 (2009).

Holzheuer, W. B.

L. Kott, W. B. Holzheuer, M. M. Wong, and G. K. Webster, “An evaluation of four commercial HPLC chiral detectors: a comparison of three polarimeters and a circular dichroism detector,” J. Pharm. Biomed. Anal. 43, 57–65 (2007).
[CrossRef]

Huang, Y.-C.

H.-J. King, C. Chou, H. Chang, and Y.-C. Huang, “Concentration measurements in chiral media using optical heterodyne polarimeter,” Opt. Commun. 110, 259–262 (1994).
[CrossRef]

King, H.-J.

H.-J. King, C. Chou, H. Chang, and Y.-C. Huang, “Concentration measurements in chiral media using optical heterodyne polarimeter,” Opt. Commun. 110, 259–262 (1994).
[CrossRef]

Kott, L.

L. Kott, W. B. Holzheuer, M. M. Wong, and G. K. Webster, “An evaluation of four commercial HPLC chiral detectors: a comparison of three polarimeters and a circular dichroism detector,” J. Pharm. Biomed. Anal. 43, 57–65 (2007).
[CrossRef]

Kuo, J. C.

E. S. Yeung, L. E. Steenhoek, S. D. Woodruff, and J. C. Kuo, “Detector based on optical activity for high performance liquid chromatographic detection of trace organics,” Anal. Chem. 52, 1399–1402 (1980).
[CrossRef]

Lama, I. M.

F. G. Sanchez, A. N. Diaz, and I. M. Lama, “Polarimetric detection in liquid chromatography: an approach to correct refractive index artefacts,” J. Liq. Chromatogr. Relat. Technol. 31, 3115–3131 (2008).
[CrossRef]

Lan, S.

S. Lan and E. Samad, “Low-birefringence lens design for polarization sensitive optical systems,” in Geometrical Optics and Lens Design, M. S. Jose and G. T. Mary, eds. (SPIE, 2006), p. 62890H.

Lazarus, H. M.

W. Rehman, L. M. Arfons, and H. M. Lazarus, “The rise, fall and subsequent triumph of thalidomide: lessons learned in drug development,” Ther. Adv. Hematol. 2, 291–308 (2011).
[CrossRef]

Lee, J.-Y.

J.-Y. Lee and D.-C. Su, “Improved common-path optical heterodyne interferometer for measuring small optical rotation angle of chiral medium,” Opt. Commun. 256, 337–341 (2005).
[CrossRef]

Lee, S.-Y.

J.-F. Lin, C.-C. Chang, C.-D. Syu, Y.-L. Lo, and S.-Y. Lee, “A new electro-optic modulated circular heterodyne interferometer for measuring the rotation angle in a chiral medium,” Opt. Lasers Eng. 47, 39–44 (2009).
[CrossRef]

Liao, K.-Y.

C. Chou, K.-H. Chiang, K.-Y. Liao, Y.-F. Chang, and C.-E. Lin, “Polarized photon-pairs heterodyne polarimetry for ultrasensitive optical activity detection of a chiral medium,” J. Phys. Chem. B 111, 9919–9922 (2007).
[CrossRef]

Lin, C.-E.

C. Chou, K.-H. Chiang, K.-Y. Liao, Y.-F. Chang, and C.-E. Lin, “Polarized photon-pairs heterodyne polarimetry for ultrasensitive optical activity detection of a chiral medium,” J. Phys. Chem. B 111, 9919–9922 (2007).
[CrossRef]

Lin, J.-F.

J.-F. Lin, C.-C. Chang, C.-D. Syu, Y.-L. Lo, and S.-Y. Lee, “A new electro-optic modulated circular heterodyne interferometer for measuring the rotation angle in a chiral medium,” Opt. Lasers Eng. 47, 39–44 (2009).
[CrossRef]

Lo, Y.-L.

J.-F. Lin, C.-C. Chang, C.-D. Syu, Y.-L. Lo, and S.-Y. Lee, “A new electro-optic modulated circular heterodyne interferometer for measuring the rotation angle in a chiral medium,” Opt. Lasers Eng. 47, 39–44 (2009).
[CrossRef]

Maystre, F.

R. Däppen, P. Voigt, F. Maystre, and A. E. Bruno, “Aspects of quantitative determinations with polarimetric detectors in liquid chromatography,” Anal. Chim. Acta 282, 47–54 (1993).
[CrossRef]

Mitsui, T.

T. Mitsui and K. Sakurai, “Precise measurement of the refractive index and optical rotatory power of a suspension by a delayed optical heterodyne technique,” Appl. Opt. 35, 2253–2258 (1996).
[CrossRef]

T. Mitsui and K. Sakurai, “Microdegree azimuth polarimeter using optical heterodyne detection,” Jpn. J. Appl. Phys. 35, 4844–4847 (1996).
[CrossRef]

Rehman, W.

W. Rehman, L. M. Arfons, and H. M. Lazarus, “The rise, fall and subsequent triumph of thalidomide: lessons learned in drug development,” Ther. Adv. Hematol. 2, 291–308 (2011).
[CrossRef]

Sakhnovskii, M.

M. Sakhnovskii and B. Timochko, “Compensation for phase and amplitude distortions introduced by a quarter-wave plate in stokes-polarimetric measurements with magneto-optical modulation,” J. Appl. Spectrosc. 65, 844–847 (1998).
[CrossRef]

Sakurai, K.

T. Mitsui and K. Sakurai, “Precise measurement of the refractive index and optical rotatory power of a suspension by a delayed optical heterodyne technique,” Appl. Opt. 35, 2253–2258 (1996).
[CrossRef]

T. Mitsui and K. Sakurai, “Microdegree azimuth polarimeter using optical heterodyne detection,” Jpn. J. Appl. Phys. 35, 4844–4847 (1996).
[CrossRef]

Samad, E.

S. Lan and E. Samad, “Low-birefringence lens design for polarization sensitive optical systems,” in Geometrical Optics and Lens Design, M. S. Jose and G. T. Mary, eds. (SPIE, 2006), p. 62890H.

Sanchez, F. G.

F. G. Sanchez, A. N. Diaz, and I. M. Lama, “Polarimetric detection in liquid chromatography: an approach to correct refractive index artefacts,” J. Liq. Chromatogr. Relat. Technol. 31, 3115–3131 (2008).
[CrossRef]

Smith, S. W.

S. W. Smith, “Chiral toxicology: it’s the same thing…only different,” Toxicol. Sci. 110, 4–30 (2009).
[CrossRef]

Steenhoek, L. E.

E. S. Yeung, L. E. Steenhoek, S. D. Woodruff, and J. C. Kuo, “Detector based on optical activity for high performance liquid chromatographic detection of trace organics,” Anal. Chem. 52, 1399–1402 (1980).
[CrossRef]

Su, D.-C.

J.-Y. Lee and D.-C. Su, “Improved common-path optical heterodyne interferometer for measuring small optical rotation angle of chiral medium,” Opt. Commun. 256, 337–341 (2005).
[CrossRef]

Syu, C.-D.

J.-F. Lin, C.-C. Chang, C.-D. Syu, Y.-L. Lo, and S.-Y. Lee, “A new electro-optic modulated circular heterodyne interferometer for measuring the rotation angle in a chiral medium,” Opt. Lasers Eng. 47, 39–44 (2009).
[CrossRef]

Timochko, B.

M. Sakhnovskii and B. Timochko, “Compensation for phase and amplitude distortions introduced by a quarter-wave plate in stokes-polarimetric measurements with magneto-optical modulation,” J. Appl. Spectrosc. 65, 844–847 (1998).
[CrossRef]

Tymiak, A. A.

Y. Zhang, D. R. Wu, D. B. Wang-Iverson, and A. A. Tymiak, “Enantioselective chromatography in drug discovery,” Drug Discov. Today 10(8), 571–577 (2005).
[CrossRef]

Voigt, P.

R. Däppen, P. Voigt, F. Maystre, and A. E. Bruno, “Aspects of quantitative determinations with polarimetric detectors in liquid chromatography,” Anal. Chim. Acta 282, 47–54 (1993).
[CrossRef]

Wang-Iverson, D. B.

Y. Zhang, D. R. Wu, D. B. Wang-Iverson, and A. A. Tymiak, “Enantioselective chromatography in drug discovery,” Drug Discov. Today 10(8), 571–577 (2005).
[CrossRef]

Webster, G. K.

L. Kott, W. B. Holzheuer, M. M. Wong, and G. K. Webster, “An evaluation of four commercial HPLC chiral detectors: a comparison of three polarimeters and a circular dichroism detector,” J. Pharm. Biomed. Anal. 43, 57–65 (2007).
[CrossRef]

Weissman, Z.

D. Goldberg and Z. Weissman, “Heterodyne polarimeter with a background subtraction system,” Application No. 20110176132 (2009).

Wong, M. M.

L. Kott, W. B. Holzheuer, M. M. Wong, and G. K. Webster, “An evaluation of four commercial HPLC chiral detectors: a comparison of three polarimeters and a circular dichroism detector,” J. Pharm. Biomed. Anal. 43, 57–65 (2007).
[CrossRef]

Woodruff, S. D.

E. S. Yeung, L. E. Steenhoek, S. D. Woodruff, and J. C. Kuo, “Detector based on optical activity for high performance liquid chromatographic detection of trace organics,” Anal. Chem. 52, 1399–1402 (1980).
[CrossRef]

Wu, D. R.

Y. Zhang, D. R. Wu, D. B. Wang-Iverson, and A. A. Tymiak, “Enantioselective chromatography in drug discovery,” Drug Discov. Today 10(8), 571–577 (2005).
[CrossRef]

Yeung, E. S.

E. S. Yeung, L. E. Steenhoek, S. D. Woodruff, and J. C. Kuo, “Detector based on optical activity for high performance liquid chromatographic detection of trace organics,” Anal. Chem. 52, 1399–1402 (1980).
[CrossRef]

Zhang, Y.

Y. Zhang, D. R. Wu, D. B. Wang-Iverson, and A. A. Tymiak, “Enantioselective chromatography in drug discovery,” Drug Discov. Today 10(8), 571–577 (2005).
[CrossRef]

Anal. Chem. (1)

E. S. Yeung, L. E. Steenhoek, S. D. Woodruff, and J. C. Kuo, “Detector based on optical activity for high performance liquid chromatographic detection of trace organics,” Anal. Chem. 52, 1399–1402 (1980).
[CrossRef]

Anal. Chim. Acta (1)

R. Däppen, P. Voigt, F. Maystre, and A. E. Bruno, “Aspects of quantitative determinations with polarimetric detectors in liquid chromatography,” Anal. Chim. Acta 282, 47–54 (1993).
[CrossRef]

Appl. Opt. (1)

Chirality (2)

W. H. De Camp, “The FDA perspective on the development of stereoisomers,” Chirality 1, 2–6 (1989).
[CrossRef]

FDA, “FDA’s policy statement for the development of new stereoisomeric drugs,” Chirality 4, 338–340 (1992).
[CrossRef]

Drug Discov. Today (1)

Y. Zhang, D. R. Wu, D. B. Wang-Iverson, and A. A. Tymiak, “Enantioselective chromatography in drug discovery,” Drug Discov. Today 10(8), 571–577 (2005).
[CrossRef]

J. Appl. Spectrosc. (1)

M. Sakhnovskii and B. Timochko, “Compensation for phase and amplitude distortions introduced by a quarter-wave plate in stokes-polarimetric measurements with magneto-optical modulation,” J. Appl. Spectrosc. 65, 844–847 (1998).
[CrossRef]

J. Liq. Chromatogr. Relat. Technol. (1)

F. G. Sanchez, A. N. Diaz, and I. M. Lama, “Polarimetric detection in liquid chromatography: an approach to correct refractive index artefacts,” J. Liq. Chromatogr. Relat. Technol. 31, 3115–3131 (2008).
[CrossRef]

J. Pharm. Biomed. Anal. (1)

L. Kott, W. B. Holzheuer, M. M. Wong, and G. K. Webster, “An evaluation of four commercial HPLC chiral detectors: a comparison of three polarimeters and a circular dichroism detector,” J. Pharm. Biomed. Anal. 43, 57–65 (2007).
[CrossRef]

J. Phys. Chem. B (1)

C. Chou, K.-H. Chiang, K.-Y. Liao, Y.-F. Chang, and C.-E. Lin, “Polarized photon-pairs heterodyne polarimetry for ultrasensitive optical activity detection of a chiral medium,” J. Phys. Chem. B 111, 9919–9922 (2007).
[CrossRef]

J. Sci. Instrum. (1)

E. J. Gillham, “A high-precision photoelectric polarimeter,” J. Sci. Instrum. 34, 435–439 (1957).
[CrossRef]

Jpn. J. Appl. Phys. (1)

T. Mitsui and K. Sakurai, “Microdegree azimuth polarimeter using optical heterodyne detection,” Jpn. J. Appl. Phys. 35, 4844–4847 (1996).
[CrossRef]

Opt. Commun. (3)

C. Chou, “A phase sensitive optical rotation measurement in a scattered chiral medium using a Zeeman laser,” Opt. Commun. 230, 259–266 (2004).
[CrossRef]

J.-Y. Lee and D.-C. Su, “Improved common-path optical heterodyne interferometer for measuring small optical rotation angle of chiral medium,” Opt. Commun. 256, 337–341 (2005).
[CrossRef]

H.-J. King, C. Chou, H. Chang, and Y.-C. Huang, “Concentration measurements in chiral media using optical heterodyne polarimeter,” Opt. Commun. 110, 259–262 (1994).
[CrossRef]

Opt. Lasers Eng. (1)

J.-F. Lin, C.-C. Chang, C.-D. Syu, Y.-L. Lo, and S.-Y. Lee, “A new electro-optic modulated circular heterodyne interferometer for measuring the rotation angle in a chiral medium,” Opt. Lasers Eng. 47, 39–44 (2009).
[CrossRef]

Ther. Adv. Hematol. (1)

W. Rehman, L. M. Arfons, and H. M. Lazarus, “The rise, fall and subsequent triumph of thalidomide: lessons learned in drug development,” Ther. Adv. Hematol. 2, 291–308 (2011).
[CrossRef]

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Figures (9)

Fig. 1.
Fig. 1.

Example of a pseudo-rotation artifact. Pseudo-rotation signals generated by an achiral molecule 2-phenylethanol. The two channels measure either a clockwise rotation (+) or a counterclockwise rotation (−). A strong signal is evident in both channels, mimicking the detection of two closely separated enantiomers. The effect was probably caused by variations in the refractive index as the analyte plug entered the flow cell. The polarimeter used was an FR model (taken from [15 with permission from Elsevier]).

Fig. 2.
Fig. 2.

Optical setup. (a) Basic scheme. The specifications of the various components can be found in the text. The angle β is the tilt angle of the analyzer. (b) Flow cell cross section. The analyte plug, which is shown entering the cell, is a solution of the analyte carried unmixed by the laminar flow of the solvent in the tube. It is usually made much longer than the cell to avoid a virtual dilution (25 mm in this case).

Fig. 3.
Fig. 3.

Direction of the electric field vector of the measurement (Em) and reference (Er) beams. represents the direction of propagation, perpendicular to the page. (a) Following the first passage through an optically active solution in the flow cell and prior to the first passage through the EO crystal. (b) Following the second passage through the EO crystal. (c) Following the second passage through the flow cell.

Fig. 4.
Fig. 4.

Processing of the raw polarimeter signal. (a) Raw square-wave signal. (b) Reference (black) and measurement (gray) after the separation and concatenation. (c) Both signals after filtration of high-frequency noise. (d) Equalization of the reference signal. (e) Net optical activity signal resulting from the subtraction of the reference signal from the measurement signal. The initial large dip is a strong pseudo-rotation signal, which is efficiently eliminated by the reference signal.

Fig. 5.
Fig. 5.

Comparing two optical amplification schemes. The OH polarimeter scheme (upper part) and the tilted analyzer gain mechanism (TAGM) scheme (lower part) used in the current paper. represents a polarization perpendicular to and “into” the page. Note that the OA angle φ is modulated by the EO crystal (not shown here, as it is not relevant to the current comparison).

Fig. 6.
Fig. 6.

Detection of a 10mg/dL D-glucose sample, on a pure water background, passing through the flow cell. The net signal shown in lower panel is the result of subtraction of the reference signal (upper right panel) from the measurement signal (upper-left panel). The rotation angle, given in the net signal panel, is estimated assuming specific rotation of 48°mL/dm×g. A pseudo-rotation signal is marked by a dashed ellipse on the measurement signal.

Fig. 7.
Fig. 7.

Detection of a 10mg/dL D-fructose sample passing through the flow cell on a background of pure water. The net signal shown in lower panel is the result of subtraction of reference signal (upper-right panel) from the measurement signal (upper left panel). The rotation angle, given in the net signal panel, is estimated assuming a specific rotation of 92.4°mL/dm×g. Pseudo-rotation signals are marked by dashed ellipses on the measurement signal.

Fig. 8.
Fig. 8.

Detection of a 1mg/dL D-glucose sample, against pure water background, passing through the flow cell. The net signal shown in the lower panel is the result of subtraction of the reference signal (upper-right panel) from the measurement signal (upper-left panel). The rotation angle given in the net signal part of the figure is estimated assuming specific rotation of 48°mL/dm×g. A pseudo-rotation signal is marked by a dashed ellipse on the measurement signal panel.

Fig. 9.
Fig. 9.

Linear relationship between the tilt angle β of the analyzer and the OA signal. The upper panel shows the net OA signal of a 100mg/dL D-glucose sample, for five angular values of the analyzer transmission axis (β). These angular tilt angles serve as a simple optical gain factor for the polarimeter signal. The goodness of fit is indicated by R2.

Equations (4)

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EAO=EAI×tA×cos(90(β+ϕ))=EAI×tA×sin(β+ϕ)EAI×tA×(β+ϕ),
IPD=EAI2×TA×(β2+2βϕ+ϕ2)EAI2×TA×(β2+2βϕ)=EAI2×TA×β2+EAI2×TA×2βϕ=Baseline+2EAI2TAβϕ,
dIPDdϕ=2EAI2TAβ.
φOA=48°mLdm×g×0.25dm×10mgdL=1200μdeg.

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