Abstract

Adaptive optics (AO) represents a powerful range of image correction technologies with proven benefits for many life-science microscopy methods. However, the complexity of adding a reflective wavefront modulator and in some cases a wavefront sensor into an already complicated microscope has made AO prohibitive for its widespread adaptation in microscopy systems. We present here the design and performance of a compact fluorescence microscope using a fully refractive optofluidic wavefront modulator, yielding imaging performance on par with that of conventional deformable mirrors, both in correction fidelity and articulation. We combine this device with a modal sensorless wavefront estimation algorithm that uses spatial frequency content of acquired images as a quality metric and thereby demonstrate a completely in-line adaptive optics microscope that can perform aberration correction up to 4th radial order of Zernike modes. This entirely new concept for adaptive optics microscopy may prove to extend the performance limits and widespread applicability of AO in life-science imaging.

© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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References

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2019 (3)

2018 (4)

K. Banerjee, P. Rajaeipour, Ç. Ataman, and H. Zappe, “Optofluidic adaptive optics,” Appl. Opt. 57(22), 6338–6344 (2018).
[Crossref]

J. M. Bueno, M. Skorsetz, S. Bonora, and P. Artal, “Wavefront correction in two-photon microscopy with a multi-actuator adaptive lens,” Opt. Express 26(11), 14278–14287 (2018).
[Crossref]

T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
[Crossref]

T. DuBose, D. Nankivil, F. LaRocca, G. Waterman, K. Hagan, J. Polans, B. Keller, D. Tran-Viet, L. Vajzovic, A. N. Kuo, C. A. Toth, J. A. Izatt, and S. Farsiu, “Handheld adaptive optics scanning laser ophthalmoscope,” Optica 5(9), 1027–1036 (2018).
[Crossref]

2017 (2)

2016 (1)

A. Tanabe, T. Hibi, S. Ipponjima, K. Matsumoto, M. Yokoyama, M. Kurihara, N. Hashimoto, and T. Nemoto, “Transmissive liquid-crystal device for correcting primary coma aberration and astigmatism in biospecimen in two-photon excitation laser scanning microscopy,” J. Biomed. Opt. 21(12), 121503 (2016).
[Crossref]

2015 (3)

2014 (3)

M. J. Booth, “Adaptive optical microscopy: the ongoing quest for a perfect image,” Light: Sci. Appl. 3(4), e165 (2014).
[Crossref]

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
[Crossref]

A. Negrean and H. D. Mansvelder, “Optimal lens design and use in laser-scanning microscopy,” Biomed. Opt. Express 5(5), 1588–1609 (2014).
[Crossref]

2012 (1)

2011 (2)

2010 (1)

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7(2), 141–147 (2010).
[Crossref]

2007 (1)

2006 (1)

2004 (1)

2002 (2)

M. J. Booth, M. A. Neil, R. Juškaitis, and T. Wilson, “Adaptive aberration correction in a confocal microscope,” Proc. Natl. Acad. Sci. 99(9), 5788–5792 (2002).
[Crossref]

L. N. Thibos, R. A. Applegate, J. T. Schwiegerling, and R. Webb, “Standards for reporting the optical aberrations of eyes,” J. Refractive Surgery 18, S652–S660 (2002).

Applegate, R. A.

L. N. Thibos, R. A. Applegate, J. T. Schwiegerling, and R. Webb, “Standards for reporting the optical aberrations of eyes,” J. Refractive Surgery 18, S652–S660 (2002).

Artal, P.

Ataman, Ç.

P. Rajaeipour, K. Banerjee, H. Zappe, and Ç. Ataman, “Optimization-based real-time open-loop control of an optofluidic refractive phase modulator,” Appl. Opt. 58(4), 1064–1072 (2019).
[Crossref]

K. Banerjee, P. Rajaeipour, Ç. Ataman, and H. Zappe, “Optofluidic adaptive optics,” Appl. Opt. 57(22), 6338–6344 (2018).
[Crossref]

K. Banerjee, P. Rajaeipour, H. Zappe, and Ç. Ataman, “Refractive opto-fluidic wavefront modulator with electrostatic push-pull actuation,” in Adaptive Optics and Wavefront Control for Biological Systems V, vol. 10886 (International Society for Optics and Photonics, 2019), p. 108860D.

P. Rajaeipour, K. Banerjee, H. Zappe, and Ç. Ataman, “Optimization-based open-loop control of phase modulators for adaptive optics,” in Adaptive Optics and Wavefront Control for Biological Systems V, vol. 10886 (International Society for Optics and Photonics, 2019), p. 108861A.

Azucena, O.

Bagwell, B. E.

B. E. Bagwell, D. V. Wick, R. Batchko, J. D. Mansell, T. Martinez, S. R. Restaino, D. M. Payne, J. Harriman, S. Serati, and G. Sharp, “Liquid crystal based active optics,” in Novel optical systems design and optimization IX, vol. 6289 (International Society for Optics and Photonics, 2006), p. 628908.

Banerjee, K.

P. Rajaeipour, K. Banerjee, H. Zappe, and Ç. Ataman, “Optimization-based real-time open-loop control of an optofluidic refractive phase modulator,” Appl. Opt. 58(4), 1064–1072 (2019).
[Crossref]

K. Banerjee, P. Rajaeipour, Ç. Ataman, and H. Zappe, “Optofluidic adaptive optics,” Appl. Opt. 57(22), 6338–6344 (2018).
[Crossref]

K. Banerjee, P. Rajaeipour, H. Zappe, and Ç. Ataman, “Refractive opto-fluidic wavefront modulator with electrostatic push-pull actuation,” in Adaptive Optics and Wavefront Control for Biological Systems V, vol. 10886 (International Society for Optics and Photonics, 2019), p. 108860D.

P. Rajaeipour, K. Banerjee, H. Zappe, and Ç. Ataman, “Optimization-based open-loop control of phase modulators for adaptive optics,” in Adaptive Optics and Wavefront Control for Biological Systems V, vol. 10886 (International Society for Optics and Photonics, 2019), p. 108861A.

Batchko, R.

B. E. Bagwell, D. V. Wick, R. Batchko, J. D. Mansell, T. Martinez, S. R. Restaino, D. M. Payne, J. Harriman, S. Serati, and G. Sharp, “Liquid crystal based active optics,” in Novel optical systems design and optimization IX, vol. 6289 (International Society for Optics and Photonics, 2006), p. 628908.

Beaurepaire, E.

Betzig, E.

T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
[Crossref]

K. Wang, W. Sun, C. T. Richie, B. K. Harvey, E. Betzig, and N. Ji, “Direct wavefront sensing for high-resolution in vivo imaging in scattering tissue,” Nat. Commun. 6(1), 7276 (2015).
[Crossref]

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
[Crossref]

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7(2), 141–147 (2010).
[Crossref]

Bonora, S.

Booth, M. J.

Boreman, G. D.

G. D. Boreman, Modulation transfer function in optical and electro-optical systems, vol. 21 (SPIEBellingham, WA, 2001).

Bronner, M. E.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
[Crossref]

Bueno, J. M.

Collins, Z. M.

T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
[Crossref]

Crest, J.

Cunniff, B.

T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
[Crossref]

Czarske, J. W.

K. Philipp, F. Lemke, S. Scholz, U. Wallrabe, M. C. Wapler, N. Koukourakis, and J. W. Czarske, “Diffraction-limited axial scanning in thick biological tissue with an aberration-correcting adaptive lens,” Sci. Rep. 9(1), 9532 (2019).
[Crossref]

Dambournet, D.

T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
[Crossref]

Davis, I.

Débarre, D.

Dobbie, I. M.

Drubin, D. G.

T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
[Crossref]

DuBose, T.

Engerer, P.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
[Crossref]

Facomprez, A.

Farsiu, S.

Forster, R.

T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
[Crossref]

Gavel, D.

Göhler, A.

Hagan, K.

Harriman, J.

B. E. Bagwell, D. V. Wick, R. Batchko, J. D. Mansell, T. Martinez, S. R. Restaino, D. M. Payne, J. Harriman, S. Serati, and G. Sharp, “Liquid crystal based active optics,” in Novel optical systems design and optimization IX, vol. 6289 (International Society for Optics and Photonics, 2006), p. 628908.

Harvey, B. K.

K. Wang, W. Sun, C. T. Richie, B. K. Harvey, E. Betzig, and N. Ji, “Direct wavefront sensing for high-resolution in vivo imaging in scattering tissue,” Nat. Commun. 6(1), 7276 (2015).
[Crossref]

Hashimoto, N.

A. Tanabe, T. Hibi, S. Ipponjima, K. Matsumoto, M. Yokoyama, M. Kurihara, N. Hashimoto, and T. Nemoto, “Transmissive liquid-crystal device for correcting primary coma aberration and astigmatism in biospecimen in two-photon excitation laser scanning microscopy,” J. Biomed. Opt. 21(12), 121503 (2016).
[Crossref]

Hibi, T.

A. Tanabe, T. Hibi, S. Ipponjima, K. Matsumoto, M. Yokoyama, M. Kurihara, N. Hashimoto, and T. Nemoto, “Transmissive liquid-crystal device for correcting primary coma aberration and astigmatism in biospecimen in two-photon excitation laser scanning microscopy,” J. Biomed. Opt. 21(12), 121503 (2016).
[Crossref]

Hiscock, T. W.

T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
[Crossref]

Hockemeyer, D.

T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
[Crossref]

Ipponjima, S.

A. Tanabe, T. Hibi, S. Ipponjima, K. Matsumoto, M. Yokoyama, M. Kurihara, N. Hashimoto, and T. Nemoto, “Transmissive liquid-crystal device for correcting primary coma aberration and astigmatism in biospecimen in two-photon excitation laser scanning microscopy,” J. Biomed. Opt. 21(12), 121503 (2016).
[Crossref]

Izatt, J. A.

Ji, N.

N. Ji, “Adaptive optical fluorescence microscopy,” Nat. Methods 14(4), 374–380 (2017).
[Crossref]

K. Wang, W. Sun, C. T. Richie, B. K. Harvey, E. Betzig, and N. Ji, “Direct wavefront sensing for high-resolution in vivo imaging in scattering tissue,” Nat. Commun. 6(1), 7276 (2015).
[Crossref]

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7(2), 141–147 (2010).
[Crossref]

Jian, Y.

Juškaitis, R.

M. J. Booth, M. A. Neil, R. Juškaitis, and T. Wilson, “Adaptive aberration correction in a confocal microscope,” Proc. Natl. Acad. Sci. 99(9), 5788–5792 (2002).
[Crossref]

Kazasidis, O.

O. Kazasidis, S. Verpoort, and U. Wittrock, “Algorithm design for image-based wavefront control without wavefront sensing,” in Optical Instrument Science, Technology, and Applications, vol. 10695 (International Society for Optics and Photonics, 2018), p. 1069502.

Keller, B.

Kirchhausen, T.

T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
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Martin, B. L.

T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
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K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
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T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
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Mumm, J.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
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K. Philipp, F. Lemke, S. Scholz, U. Wallrabe, M. C. Wapler, N. Koukourakis, and J. W. Czarske, “Diffraction-limited axial scanning in thick biological tissue with an aberration-correcting adaptive lens,” Sci. Rep. 9(1), 9532 (2019).
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Reinig, M.

Restaino, S. R.

B. E. Bagwell, D. V. Wick, R. Batchko, J. D. Mansell, T. Martinez, S. R. Restaino, D. M. Payne, J. Harriman, S. Serati, and G. Sharp, “Liquid crystal based active optics,” in Novel optical systems design and optimization IX, vol. 6289 (International Society for Optics and Photonics, 2006), p. 628908.

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Saxena, A.

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11(6), 625–628 (2014).
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T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
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K. Philipp, F. Lemke, S. Scholz, U. Wallrabe, M. C. Wapler, N. Koukourakis, and J. W. Czarske, “Diffraction-limited axial scanning in thick biological tissue with an aberration-correcting adaptive lens,” Sci. Rep. 9(1), 9532 (2019).
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B. E. Bagwell, D. V. Wick, R. Batchko, J. D. Mansell, T. Martinez, S. R. Restaino, D. M. Payne, J. Harriman, S. Serati, and G. Sharp, “Liquid crystal based active optics,” in Novel optical systems design and optimization IX, vol. 6289 (International Society for Optics and Photonics, 2006), p. 628908.

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B. E. Bagwell, D. V. Wick, R. Batchko, J. D. Mansell, T. Martinez, S. R. Restaino, D. M. Payne, J. Harriman, S. Serati, and G. Sharp, “Liquid crystal based active optics,” in Novel optical systems design and optimization IX, vol. 6289 (International Society for Optics and Photonics, 2006), p. 628908.

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T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
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T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
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T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
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K. Philipp, F. Lemke, S. Scholz, U. Wallrabe, M. C. Wapler, N. Koukourakis, and J. W. Czarske, “Diffraction-limited axial scanning in thick biological tissue with an aberration-correcting adaptive lens,” Sci. Rep. 9(1), 9532 (2019).
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T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
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K. Wang, W. Sun, C. T. Richie, B. K. Harvey, E. Betzig, and N. Ji, “Direct wavefront sensing for high-resolution in vivo imaging in scattering tissue,” Nat. Commun. 6(1), 7276 (2015).
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K. Philipp, F. Lemke, S. Scholz, U. Wallrabe, M. C. Wapler, N. Koukourakis, and J. W. Czarske, “Diffraction-limited axial scanning in thick biological tissue with an aberration-correcting adaptive lens,” Sci. Rep. 9(1), 9532 (2019).
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B. E. Bagwell, D. V. Wick, R. Batchko, J. D. Mansell, T. Martinez, S. R. Restaino, D. M. Payne, J. Harriman, S. Serati, and G. Sharp, “Liquid crystal based active optics,” in Novel optical systems design and optimization IX, vol. 6289 (International Society for Optics and Photonics, 2006), p. 628908.

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Wittrock, U.

O. Kazasidis, S. Verpoort, and U. Wittrock, “Algorithm design for image-based wavefront control without wavefront sensing,” in Optical Instrument Science, Technology, and Applications, vol. 10695 (International Society for Optics and Photonics, 2018), p. 1069502.

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T.-L. Liu, S. Upadhyayula, D. E. Milkie, V. Singh, K. Wang, I. A. Swinburne, K. R. Mosaliganti, Z. M. Collins, T. W. Hiscock, J. Shea, A. Q. Kohrman, T. N. Medwig, D. Dambournet, R. Forster, B. Cunniff, Y. Ruan, H. Yashiro, S. Scholpp, E. M. Meyerowitz, D. Hockemeyer, D. G. Drubin, B. L. Martin, D. Q. Matus, M. Koyama, S. G. Megason, T. Kirchhausen, and E. Betzig, “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms,” Science 360(6386), eaaq1392 (2018).
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Zappe, H.

P. Rajaeipour, K. Banerjee, H. Zappe, and Ç. Ataman, “Optimization-based real-time open-loop control of an optofluidic refractive phase modulator,” Appl. Opt. 58(4), 1064–1072 (2019).
[Crossref]

K. Banerjee, P. Rajaeipour, Ç. Ataman, and H. Zappe, “Optofluidic adaptive optics,” Appl. Opt. 57(22), 6338–6344 (2018).
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Figures (9)

Fig. 1.
Fig. 1. Evolution of the conventional AO microscopy setups from: (a) requiring at least 2 telescopes and folded paths due to having a Deformable Mirror (DM) and a Wavefront Sensor (WS) to (b) the proposed configuration in this study which employs a Deformable Phase Plate (DPP) and requires only one telescope.
Fig. 2.
Fig. 2. Compact and all-in-line fluorescence microscope with sensorless AO aberration correction. (a) Schematics of the system design and the employed refractive wavefront modulator (DPP). (b) A fabricated DPP and The realized AO microscope. PP: phase plate, OL: objective lens, F: filter, L1-L4: telescope lenses, TL: tube lens.
Fig. 3.
Fig. 3. (a) Sample implementation of the $2N+1$ algorithm for estimating an aberration mode with 2 iterations (in this case $N=1$). Data points are calculated by applying an additional bias aberration in the form of the analysed mode using the wavefront modulator and scoring the captured images. Asterisks depict the scores of the captured images by sweeping the amplitude of the applied oblique astigmatism. The quality metric spatial frequency range is shown on the PSD plots as an annular ring. (b) Summarized flowchart of the modal decomposition-based aberration estimation algorithm.
Fig. 4.
Fig. 4. (a) Knife-edge method for MTF measurement of the microscope thorough calculation of Edge Spread Function (ESF). (b) Image-space MTF of the developed AO microscope at different positions of the FoV before installing the DPP (red), after installing it while it is all off (green) and after performing AO correction by sensorless estimation of the initial system aberrations (blue). (c) Zernike decomposition of the estimated initial aberrations at 3 different positions of the FoV. (d) Image of a single fluorescent bead with a nominal diameter of 1 µm at different positions of the FoV before and after correcting for the estimated initial wavefront error of the fluorescence microscope. The line plots are calculated by averaging 4 equally-spaced cross-sections of the image of beads and transforming the distance to object space.
Fig. 5.
Fig. 5. Examples of correcting for known aberrations. (a) The line plot depicts the residual wavefront RMSE with respect to the applied aberrations after compensating for the system initial aberrations. (b) The bar plots show the applied and estimated aberrations. The first row of the figures show the frames that are aberrated by the wavefront errors shown in the bar plots. The bottom row frames show the corrected frames of each corresponding top aberrated frame.
Fig. 6.
Fig. 6. Illustration of the progressive improvement in the image quality after each iteration of the aberration estimation algorithm. (a) The bar plots show the evolution of estimated wavefront towards the actual applied error. The residual RMSE after each iteration is depicted below the plots. (b) The captured frames and their normalized PSD with corresponding score starting from the unaberrated condition towards the corrected frame after 5 iterations. The considered spatial frequency range for the image quality metric is depicted on the PSD plots in form of an annular ring.
Fig. 7.
Fig. 7. Results of voltage hold and voltage cycling for stability test of the DPP. (a) Interferometric measurement of the peak to valley of replicating a random wavefront by holding the applied voltages to the DPP electrodes for an extended period of time. Profile of the measured wavefront at $t=0$ min is depicted on the plot. (b) Aberrated and (c) corrected images of 4$^{th}$ to 6$^{th}$ line elements of group 7 of a 1951 USAF target sample before the voltage cycling test. (d) Aberrated and (e) corrected images of the same line elements after switching the driving voltage on all electrodes of the modulator for 200 cycles over 60 seconds. (e) Obtained by applying the voltage signals calculated before the cycling process. (f) Cross-sections of the 6$^{th}$ line elements of group 7 in the 4 stated conditions.
Fig. 8.
Fig. 8. (a) Aberrated image of a 1951 USAF target due to placing a custom phase plate on top of the target. (b) By estimating the aberrations and performing AO correction the image quality is retrieved and the PSD of the image includes higher spatial frequency content compared to the PSD of the aberrated image. Line elements at the right and top-left of the image correspond to groups 6 and 7 of the target. The annular rings on the normalized PSD plots depict the spatial frequencies between 1% to 35% of the cut-off frequency, considered for the image quality metric. (c) Intensity profiles at 3 marked regions of the target before (circles) and after (asterisks) AO correction. (d) Zernike decomposition of the applied correction.
Fig. 9.
Fig. 9. Human cheek cells imaged behind an aberrating phase plate by the developed AO-microscope. (a) Unaberrated images of the cells after correcting for the aberrations induced by the initial wavefront modulator flatness error and potential spherical aberration due to the 170 $\mu m$ thick cover slip. (b) Aberrated images which are distorted by placing an aberrating phase plate on top of the cover slip. (c) The corrected images which retrieve the resolvability of the cheek cell details and (d) the Zernike decomposition of the applied corrections.