Dual-Beam Laser Traps, Optical Stretcher, Optical Cell Rotator

fig1_os-principle
Figure 1: Schematic of the serial trapping and stretching of cells in the OS. a) Cells (yellow) are delivered to the trapping region by means of a microfluidic channel. Low-intensity Gaussian laser beams (red) emanating from two opposing optical fibers initially capture the cell by subjecting it to scattering and gradient forces directed towards the center of the optical trap. b) Once the cell is stably trapped, the laser intensity is increased so that the resulting optical surface forces are strong enough to deform the cell.

Optical trapping employs forces generated by light to spatially immobilize suspended objects in a contact-free manner. Arthur Ashkin was the first to demonstrate that microscopic objects can be trapped and manipulated with light. He went on to create a stable trap using two counter-propagating laser beams – the first dual-beam laser trap (DBLT) [1]. 16 years later, he also introduced optical tweezers, which utilize the forces of a single, focused laser beam [2]. In 1993, based on Ashkin’s early dual-beam work, Mara Prentiss and co-workers created the first DBLT employing two opposing optical fibers [3]. As the trapping optics of the fiber-based DBLT are completely separated from the microscope optics, DBLTs then became an extremely versatile tool for the micro-manipulation of biological samples. They are also easily combined with microfluidic lab-on-chip systems for efficient delivery of trapping objects.

Previous work in our lab [4] demonstrated that the optical forces in a dual-beam laser traps can be used to deform and measure soft materials in a controlled manner. When used for this purpose, DBLTs have come to be known as an optical stretcher (OS). An illustration of the trapping and deformation of a cell in the OS is shown in Figure 1. We have used the OS extensively to measure the viscoelastic properties of various cell types and have established cell deformability as a marker of cell function [5, 6, 7, 8, 9, 10, 11, 12]. Along the way we had improved the throughput of the OS to hundreds of cells per hour by combining it with microfluidic assemblies [13, 14]. With the advent of real-time deformability cytometry (RT-DC), with its 10,000x higher throughput, the OS has increasingly been repurposed for the high-content study of rare or sensitive objects, such as phospholipid vesicles [15] or isolated cell nuclei [16]. Previously, it had also been used to test the axial light transmission through individual cells, e.g. by gently trapping and aligning living Muller cells along their optical axis without any mechanical contact [17].

fig2_rotor
Figure 2: Schematic of the optical cell rotator. The rotational orientation of the cell is acquired by changing the orientation of the double-lobed mode profile prior to coupling it to the few-mode fiber.

In current studies, we use DBLTs for the controlled rotation of single cells in an optical cell rotator (OCR) [18]. In the OCR, the output of one of the fibers, which is a few-mode fiber, is controlled by a spatial light modulator to achieve a rotating double-lobed mode profile (Figure 2). The optical forces induced by the rotating mode result in a rotation of the trapped cell. Rotating single cells about an axis perpendicular to the optical axis of a microscope allows the acquisition of tomographic data sets of individual cells. Besides the all-optical rotation in the OCR we also employ a combination of optical trapping in a DBLT with drag forces induced by flow in a microfluidic channel for a contact free optofluidic rotation of individual cells, as proposed by Kolb et al. [19]. We use these techniques together with QPI and ODT to determine 3D refractive index maps of individual cells [20].
All these examples showcase the versatility of DBLTs and propose it as a high-content tool for single cell studies.

  1. A. Ashkin, “Acceleration and trapping of particles by radiation pressure,” Physical Review Letters, vol. 24, pp. 156-159, 1970. doi:10.1103/PhysRevLett.24.156
    [BibTeX] [Download PDF]

    @Article{Ashkin1970,
    Title = {Acceleration and Trapping of Particles by Radiation Pressure},
    Author = {Ashkin, A.},
    Journal = {{Physical Review Letters}},
    Year = {1970},
    Month = {Jan},
    Pages = {156--159},
    Volume = {24},
    Doi = {10.1103/PhysRevLett.24.156},
    Issue = {4},
    Numpages = {0},
    Publisher = {American Physical Society},
    Url = {http://link.aps.org/doi/10.1103/PhysRevLett.24.156}
    }

  2. A. Ashkin, J. M. Dziedzic, J. E. Bjorkholm, and S. Chu, “Observation of a single-beam gradient force optical trap for dielectric particles,” Optics Letters, vol. 11, iss. 5, pp. 288-290, 1986. doi:10.1364/OL.11.000288
    [BibTeX] [Abstract] [Download PDF]

    Optical trapping of dielectric particles by a single-beam gradient force trap was demonstrated for the first reported time. This confirms the concept of negative light pressure due to the gradient force. Trapping was observed over the entire range of particle size from 10 $\mu$m to ~25 nm in water. Use of the new trap extends the size range of macroscopic particles accessible to optical trapping and manipulation well into the Rayleigh size regime. Application of this trapping principle to atom trapping is considered.

    @Article{Ashkin1986,
    Title = {Observation of a single-beam gradient force optical trap for dielectric particles},
    Author = {A. Ashkin and J. M. Dziedzic and J. E. Bjorkholm and Steven Chu},
    Journal = {{Optics Letters}},
    Year = {1986},
    Month = {May},
    Number = {5},
    Pages = {288--290},
    Volume = {11},
    Abstract = {Optical trapping of dielectric particles by a single-beam gradient force trap was demonstrated for the first reported time. This confirms the concept of negative light pressure due to the gradient force. Trapping was observed over the entire range of particle size from 10 $\mu$m to ~25 nm in water. Use of the new trap extends the size range of macroscopic particles accessible to optical trapping and manipulation well into the Rayleigh size regime. Application of this trapping principle to atom trapping is considered.},
    Doi = {10.1364/OL.11.000288},
    Publisher = {OSA},
    Url = {http://ol.osa.org/abstract.cfm?URI=ol-11-5-288}
    }

  3. A. Constable, J. Kim, J. Mervis, F. Zarinetchi, and M. Prentiss, “Demonstration of a fiber-optical light-force trap,” Optics Letters, vol. 18, iss. 21, pp. 1867-1869, 1993. doi:10.1364/OL.18.001867
    [BibTeX] [Abstract] [Download PDF]

    We demonstrate a fiber-optical version of a stable three-dimensional light-force trap, which we have used to hold and manipulate small dielectric spheres and living yeast. We show that the trap can be constructed by use of infrared diode lasers with fiber pigtails, without any external optics.

    @Article{Constable1993,
    Title = {Demonstration of a fiber-optical light-force trap},
    Author = {A. Constable and Jinha Kim and J. Mervis and F. Zarinetchi and M. Prentiss},
    Journal = {{Optics Letters}},
    Year = {1993},
    Month = {Nov},
    Number = {21},
    Pages = {1867--1869},
    Volume = {18},
    Abstract = {We demonstrate a fiber-optical version of a stable three-dimensional light-force trap, which we have used to hold and manipulate small dielectric spheres and living yeast. We show that the trap can be constructed by use of infrared diode lasers with fiber pigtails, without any external optics.},
    Doi = {10.1364/OL.18.001867},
    Publisher = {OSA},
    Url = {http://ol.osa.org/abstract.cfm?URI=ol-18-21-1867}
    }

  4. J. Guck, R. Ananthakrishnan, T. J. Moon, C. C. Cunningham, and J. Käs, “Optical deformability of soft biological dielectrics,” Physical Review Letters, vol. 84, iss. 23, pp. 5451-5454, 2000. doi:10.1103/physrevlett.84.5451
    [BibTeX] [Download PDF]

    @Article{Guck2000,
    Title = {Optical Deformability of Soft Biological Dielectrics},
    Author = {J. Guck and R. Ananthakrishnan and T. J. Moon and C. C. Cunningham and J. Käs},
    Journal = {{Physical Review Letters}},
    Year = {2000},
    Month = {jun},
    Number = {23},
    Pages = {5451--5454},
    Volume = {84},
    Doi = {10.1103/physrevlett.84.5451},
    Publisher = {American Physical Society ({APS})},
    Url = {http://dx.doi.org/10.1103/physrevlett.84.5451}
    }

  5. J. Guck, R. Ananthakrishnan, H. Mahmood, T. J. Moon, C. C. Cunningham, and J. Käs, “The optical stretcher: a novel laser tool to micromanipulate cells,” Biophysical Journal, vol. 81, iss. 2, pp. 767-784, 2001. doi:10.1016/s0006-3495(01)75740-2
    [BibTeX] [Download PDF]

    @Article{Guck2001,
    Title = {The Optical Stretcher: A Novel Laser Tool to Micromanipulate Cells},
    Author = {Jochen Guck and Revathi Ananthakrishnan and Hamid Mahmood and Tess J. Moon and C. Casey Cunningham and Josef Käs},
    Journal = {{Biophysical Journal}},
    Year = {2001},
    Month = {aug},
    Number = {2},
    Pages = {767--784},
    Volume = {81},
    Doi = {10.1016/s0006-3495(01)75740-2},
    Publisher = {Elsevier {BV}},
    Url = {http://dx.doi.org/10.1016/s0006-3495(01)75740-2}
    }

  6. J. Guck, S. Schinkinger, B. Lincoln, F. Wottawah, S. Ebert, M. Romeyke, D. Lenz, H. M. Erickson, R. Ananthakrishnan, D. Mitchell, J. Käs, S. Ulvick, and C. Bilby, “Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence,” Biophysical Journal, vol. 88, iss. 5, pp. 3689-3698, 2005. doi:10.1529/biophysj.104.045476
    [BibTeX] [Download PDF]

    @Article{Guck2005,
    Title = {Optical Deformability as an Inherent Cell Marker for Testing Malignant Transformation and Metastatic Competence},
    Author = {Jochen Guck and Stefan Schinkinger and Bryan Lincoln and Falk Wottawah and Susanne Ebert and Maren Romeyke and Dominik Lenz and Harold M. Erickson and Revathi Ananthakrishnan and Daniel Mitchell and Josef Käs and Sydney Ulvick and Curt Bilby},
    Journal = {{Biophysical Journal}},
    Year = {2005},
    Month = {may},
    Number = {5},
    Pages = {3689--3698},
    Volume = {88},
    Doi = {10.1529/biophysj.104.045476},
    Publisher = {Elsevier {BV}},
    Url = {https://doi.org/10.1529%2Fbiophysj.104.045476}
    }

  7. T. W. Remmerbach, F. Wottawah, J. Dietrich, B. Lincoln, C. Wittekind, and J. Guck, “Oral cancer diagnosis by mechanical phenotyping,” Cancer Research, vol. 69, iss. 5, pp. 1728-1732, 2009. doi:10.1158/0008-5472.CAN-08-4073
    [BibTeX] [Download PDF]

    @Article{Remmerbach2009,
    Title = {Oral cancer diagnosis by mechanical phenotyping},
    Author = {Remmerbach, Torsten W and Wottawah, Falk and Dietrich, Julia and Lincoln, Bryan and Wittekind, Christian and Guck, Jochen},
    Journal = {{Cancer Research}},
    Year = {2009},
    Number = {5},
    Pages = {1728--1732},
    Volume = {69},
    Doi = {10.1158/0008-5472.CAN-08-4073},
    Publisher = {{American Association for Cancer Research}},
    Url = {http://cancerres.aacrjournals.org/content/69/5/1728.full-text.pdf}
    }

  8. F. Lautenschläger, S. Paschke, S. Schinkinger, A. Bruel, M. Beil, and J. Guck, “The regulatory role of cell mechanics for migration of differentiating myeloid cells,” Proceedings of the National Academy of Sciences, vol. 106, iss. 37, pp. 15696-15701, 2009. doi:10.1073/pnas.0811261106
    [BibTeX]

    @Article{Lautenschlager2009,
    Title = {The regulatory role of cell mechanics for migration of differentiating myeloid cells},
    Author = {Lautenschl{\"a}ger, Franziska and Paschke, Stephan and Schinkinger, Stefan and Bruel, Arlette and Beil, Michael and Guck, Jochen},
    Journal = {{Proceedings of the National Academy of Sciences}},
    Year = {2009},
    Number = {37},
    Pages = {15696--15701},
    Volume = {106},
    Doi = {10.1073/pnas.0811261106},
    Publisher = {National Acad Sciences}
    }

  9. A. E. Ekpenyong, G. Whyte, K. Chalut, S. Pagliara, F. Lautenschläger, C. Fiddler, S. Paschke, U. F. Keyser, E. R. Chilvers, and J. Guck, “Viscoelastic properties of differentiating blood cells are fate-and function-dependent,” PLoS One, vol. 7, iss. 9, p. e45237, 2012. doi:10.1371/journal.pone.0045237
    [BibTeX] [Download PDF]

    @Article{Ekpenyong2012,
    Title = {Viscoelastic properties of differentiating blood cells are fate-and function-dependent},
    Author = {Ekpenyong, Andrew E and Whyte, Graeme and Chalut, Kevin and Pagliara, Stefano and Lautenschl{\"a}ger, Franziska and Fiddler, Christine and Paschke, Stephan and Keyser, Ulrich F and Chilvers, Edwin R and Guck, Jochen},
    Journal = {{PLoS One}},
    Year = {2012},
    Number = {9},
    Pages = {e45237},
    Volume = {7},
    Doi = {10.1371/journal.pone.0045237},
    Owner = {paul},
    Publisher = {Public Library of Science},
    Timestamp = {2017.04.24},
    Url = {http://journals.plos.org/plosone/article/asset?id=10.1371/journal.pone.0045237.PDF}
    }

  10. H. K. Matthews, U. Delabre, J. L. Rohn, J. Guck, P. Kunda, and B. Baum, “Changes in ect2 localization couple actomyosin-dependent cell shape changes to mitotic progression,” Developmental cell, vol. 23, iss. 2, pp. 371-383, 2012. doi:10.1016/j.devcel.2012.06.003
    [BibTeX] [Download PDF]

    @Article{Matthews2012,
    Title = {Changes in Ect2 localization couple actomyosin-dependent cell shape changes to mitotic progression},
    Author = {Matthews, Helen K and Delabre, Ulysse and Rohn, Jennifer L and Guck, Jochen and Kunda, Patricia and Baum, Buzz},
    Journal = {Developmental Cell},
    Year = {2012},
    Number = {2},
    Pages = {371--383},
    Volume = {23},
    Doi = {10.1016/j.devcel.2012.06.003},
    Publisher = {{Cell Press}},
    Url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763371/pdf/main.pdf}
    }

  11. S. M. Man, A. Ekpenyong, P. Tourlomousis, S. Achouri, E. Cammarota, K. Hughes, A. Rizzo, G. Ng, J. A. Wright, P. Cicuta, J. R. Guck, and C. E. Bryant, “Actin polymerization as a key innate immune effector mechanism to controlSalmonellainfection,” Proceedings of the National Academy of Sciences, vol. 111, iss. 49, pp. 17588-17593, 2014. doi:10.1073/pnas.1419925111
    [BibTeX]

    @Article{Man2014,
    Title = {Actin polymerization as a key innate immune effector mechanism to {controlSalmonellainfection}},
    Author = {Si Ming Man and Andrew Ekpenyong and Panagiotis Tourlomousis and Sarra Achouri and Eugenia Cammarota and Katherine Hughes and Alessandro Rizzo and Gilbert Ng and John A. Wright and Pietro Cicuta and Jochen R. Guck and Clare E. Bryant},
    Journal = {{Proceedings of the National Academy of Sciences}},
    Year = {2014},
    Month = {nov},
    Number = {49},
    Pages = {17588--17593},
    Volume = {111},
    Doi = {10.1073/pnas.1419925111},
    Owner = {paul},
    Publisher = {{Proceedings of the National Academy of Sciences}},
    Timestamp = {2017.04.24}
    }

  12. C. J. Chan, A. E. Ekpenyong, S. Golfier, W. Li, K. J. Chalut, O. Otto, J. Elgeti, J. Guck, and F. Lautenschläger, “Myosin ii activity softens cells in suspension,” Biophysical journal, vol. 108, iss. 8, pp. 1856-1869, 2015. doi:10.1016/j.bpj.2015.03.009
    [BibTeX] [Download PDF]

    @Article{Chan2015,
    Title = {Myosin II Activity Softens Cells in Suspension},
    Author = {Chan, Chii J and Ekpenyong, Andrew E and Golfier, Stefan and Li, Wenhong and Chalut, Kevin J and Otto, Oliver and Elgeti, Jens and Guck, Jochen and Lautenschl{\"a}ger, Franziska},
    Journal = {Biophysical Journal},
    Year = {2015},
    Number = {8},
    Pages = {1856--1869},
    Volume = {108},
    Doi = {10.1016/j.bpj.2015.03.009},
    Publisher = {{Cell Press}},
    Url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407259/pdf/main.pdf}
    }

  13. B. Lincoln, H. M. Erickson, S. Schinkinger, F. Wottawah, D. Mitchell, S. Ulvick, C. Bilby, and J. Guck, “Deformability-based flow cytometry,” Cytometry Part A, vol. 59A, iss. 2, pp. 203-209, 2004. doi:10.1002/cyto.a.20050
    [BibTeX] [Download PDF]

    @Article{Lincoln2004,
    Title = {Deformability-based flow cytometry},
    Author = {Lincoln, Bryan and Erickson, Harold M. and Schinkinger, Stefan and Wottawah, Falk and Mitchell, Daniel and Ulvick, Sydney and Bilby, Curt and Guck, Jochen},
    Journal = {{Cytometry Part A}},
    Year = {2004},
    Number = {2},
    Pages = {203--209},
    Volume = {59A},
    Doi = {10.1002/cyto.a.20050},
    ISSN = {1552-4930},
    Keywords = {optical stretcher, cell marker, diagnosis, microfluidics, breast cancer, metastasis, stem cells, RBC, PMN, optical deformability},
    Publisher = {Wiley Subscription Services, Inc., A Wiley Company},
    Url = {http://dx.doi.org/10.1002/cyto.a.20050}
    }

  14. C. Faigle, F. Lautenschläger, G. Whyte, P. Homewood, E. Martín-Badosa, and J. Guck, “A monolithic glass chip for active single-cell sorting based on mechanical phenotyping,” Lab on a Chip, vol. 15, iss. 5, pp. 1267-1275, 2015. doi:10.1039/c4lc01196a
    [BibTeX] [Download PDF]

    @Article{Faigle2015,
    Title = {A monolithic glass chip for active single-cell sorting based on mechanical phenotyping},
    Author = {Christoph Faigle and Franziska Lautenschläger and Graeme Whyte and Philip Homewood and Estela Mart{\'{\i}}n-Badosa and Jochen Guck},
    Journal = {{Lab on a Chip}},
    Year = {2015},
    Number = {5},
    Pages = {1267--1275},
    Volume = {15},
    Doi = {10.1039/c4lc01196a},
    Publisher = {Royal Society of Chemistry ({RSC})},
    Url = {https://doi.org/10.1039%2Fc4lc01196a}
    }

  15. U. Delabre, K. Feld, E. Crespo, G. Whyte, C. Sykes, U. Seifert, and J. Guck, “Deformation of phospholipid vesicles in an optical stretcher,” Soft matter, vol. 11, iss. 30, pp. 6075-6088, 2015. doi:10.1039/C5SM00562K
    [BibTeX]

    @Article{Delabre2015,
    Title = {Deformation of phospholipid vesicles in an optical stretcher},
    Author = {Delabre, Ulysse and Feld, Kasper and Crespo, Eleonore and Whyte, Graeme and Sykes, Cecile and Seifert, Udo and Guck, Jochen},
    Journal = {Soft Matter},
    Year = {2015},
    Number = {30},
    Pages = {6075--6088},
    Volume = {11},
    Doi = {10.1039/C5SM00562K},
    Publisher = {{Royal Society of Chemistry}}
    }

  16. C. J. Chan, W. Li, G. Cojoc, and J. Guck, “Volume transitions of isolated cell nuclei induced by rapid temperature increase,” Biophysical Journal, vol. 112, iss. 6, pp. 1063-1076, 2017. doi:/10.1016/j.bpj.2017.01.022
    [BibTeX]

    @Article{Chan2017,
    Title = {Volume Transitions of Isolated Cell Nuclei Induced by Rapid Temperature Increase},
    Author = {Chan, Chii J and Li, Wenhong and Cojoc, Gheorghe and Guck, Jochen},
    Journal = {{Biophysical Journal}},
    Year = {2017},
    Number = {6},
    Pages = {1063--1076},
    Volume = {112},
    Doi = {/10.1016/j.bpj.2017.01.022},
    Publisher = {Elsevier}
    }

  17. K. Franze, J. Grosche, S. N. Skatchkov, S. Schinkinger, C. Foja, D. Schild, O. Uckermann, K. Travis, A. Reichenbach, and J. Guck, “Müller cells are living optical fibers in the vertebrate retina,” Proceedings of the National Academy of Sciences, vol. 104, iss. 20, pp. 8287-8292, 2007. doi:10.1073/pnas.0611180104
    [BibTeX] [Abstract] [Download PDF]

    Although biological cells are mostly transparent, they are phase objects that differ in shape and refractive index. Any image that is projected through layers of randomly oriented cells will normally be distorted by refraction, reflection, and scattering. Counterintuitively, the retina of the vertebrate eye is inverted with respect to its optical function and light must pass through several tissue layers before reaching the light-detecting photoreceptor cells. Here we report on the specific optical properties of glial cells present in the retina, which might contribute to optimize this apparently unfavorable situation. We investigated intact retinal tissue and individual M�ller cells, which are radial glial cells spanning the entire retinal thickness. M�ller cells have an extended funnel shape, a higher refractive index than their surrounding tissue, and are oriented along the direction of light propagation. Transmission and reflection confocal microscopy of retinal tissue in vitro and in vivo showed that these cells provide a low-scattering passage for light from the retinal surface to the photoreceptor cells. Using a modified dual-beam laser trap we could also demonstrate that individual M�ller cells act as optical fibers. Furthermore, their parallel array in the retina is reminiscent of fiberoptic plates used for low-distortion image transfer. Thus, M�ller cells seem to mediate the image transfer through the vertebrate retina with minimal distortion and low loss. This finding elucidates a fundamental feature of the inverted retina as an optical system and ascribes a new function to glial cells.

    @Article{Franze2007,
    Title = {Müller cells are living optical fibers in the vertebrate retina},
    Author = {Franze, Kristian and Grosche, Jens and Skatchkov, Serguei N. and Schinkinger, Stefan and Foja, Christian and Schild, Detlev and Uckermann, Ortrud and Travis, Kort and Reichenbach, Andreas and Guck, Jochen},
    Journal = {{Proceedings of the National Academy of Sciences}},
    Year = {2007},
    Number = {20},
    Pages = {8287-8292},
    Volume = {104},
    Abstract = {Although biological cells are mostly transparent, they are phase objects that differ in shape and refractive index. Any image that is projected through layers of randomly oriented cells will normally be distorted by refraction, reflection, and scattering. Counterintuitively, the retina of the vertebrate eye is inverted with respect to its optical function and light must pass through several tissue layers before reaching the light-detecting photoreceptor cells. Here we report on the specific optical properties of glial cells present in the retina, which might contribute to optimize this apparently unfavorable situation. We investigated intact retinal tissue and individual M�ller cells, which are radial glial cells spanning the entire retinal thickness. M�ller cells have an extended funnel shape, a higher refractive index than their surrounding tissue, and are oriented along the direction of light propagation. Transmission and reflection confocal microscopy of retinal tissue in vitro and in vivo showed that these cells provide a low-scattering passage for light from the retinal surface to the photoreceptor cells. Using a modified dual-beam laser trap we could also demonstrate that individual M�ller cells act as optical fibers. Furthermore, their parallel array in the retina is reminiscent of fiberoptic plates used for low-distortion image transfer. Thus, M�ller cells seem to mediate the image transfer through the vertebrate retina with minimal distortion and low loss. This finding elucidates a fundamental feature of the inverted retina as an optical system and ascribes a new function to glial cells.},
    Doi = {10.1073/pnas.0611180104},
    Eprint = {http://www.pnas.org/content/104/20/8287.full.pdf},
    Url = {http://www.pnas.org/content/104/20/8287.abstract}
    }

  18. M. Kreysing, D. Ott, M. J. Schmidberger, O. Otto, M. Sch�rmann, E. Martín-Badosa, G. Whyte, and J. Guck, “Dynamic operation of optical fibres beyond the single-mode regime facilitates the orientation of biological cells,” Nature Communications, vol. 5, p. 5481, 2014. doi:10.1038/ncomms6481
    [BibTeX] [Download PDF]

    @Article{Kreysing2014,
    Title = {Dynamic operation of optical fibres beyond the single-mode regime facilitates the orientation of biological cells},
    Author = {Moritz Kreysing and Dino Ott and Michael J. Schmidberger and Oliver Otto and Mirjam Sch�rmann and Estela Mart{\'{\i}}n-Badosa and Graeme Whyte and Jochen Guck},
    Journal = {{Nature Communications}},
    Year = {2014},
    Month = {nov},
    Pages = {5481},
    Volume = {5},
    Doi = {10.1038/ncomms6481},
    Publisher = {Springer Nature},
    Url = {http://dx.doi.org/10.1038/ncomms6481}
    }

  19. T. Kolb, S. Albert, M. Haug, and G. Whyte, “Dynamically reconfigurable fibre optical spanner,” Lab on a Chip, vol. 14, iss. 6, pp. 1186-1190, 2014. doi:10.1039/c3lc51277k
    [BibTeX] [Download PDF]

    @Article{Kolb2014,
    Title = {Dynamically reconfigurable fibre optical spanner},
    Author = {Thorsten Kolb and Sahradha Albert and Michael Haug and Graeme Whyte},
    Journal = {{Lab on a Chip}},
    Year = {2014},
    Number = {6},
    Pages = {1186--1190},
    Volume = {14},
    Doi = {10.1039/c3lc51277k},
    Publisher = {Royal Society of Chemistry ({RSC})},
    Url = {https://doi.org/10.1039%2Fc3lc51277k}
    }

  20. P. Müller, M. Schürmann, C. J. Chan, and J. Guck, “Single-cell diffraction tomography with optofluidic rotation about a tilted axis,” Proc. SPIE, vol. 9548, p. 95480U-95480U-5, 2015. doi:10.1117/12.2191501
    [BibTeX] [Abstract] [Download PDF]

    Optical diffraction tomography (ODT) is a tomographic technique that can be used to measure the three-dimensional (3D) refractive index distribution within living cells without the requirement of any marker. In principle, ODT can be regarded as a generalization of optical projection tomography which is equivalent to computerized tomography (CT). Both optical tomographic techniques require projection-phase images of cells measured at multiple angles. However, the reconstruction of the 3D refractive index distribution post-measurement differs for the two techniques. It is known that ODT yields better results than projection tomography, because it takes into account diffraction of the imaging light due to the refractive index structure of the sample. Here, we apply ODT to biological cells in a microfluidic chip which combines optical trapping and microfluidic flow to achieve an optofluidic single-cell rotation. In particular, we address the problem that arises when the trapped cell is not rotating about an axis perpendicular to the imaging plane, but is instead arbitrarily tilted. In this paper we show that the 3D reconstruction can be improved by taking into account such a tilted rotational axis in the reconstruction process.

    @Article{Mueller2015,
    Title = {Single-cell diffraction tomography with optofluidic rotation about a tilted axis},
    Author = {Müller, Paul and Schürmann, Mirjam and Chan, Chii J. and Guck, Jochen},
    Journal = {{Proc. SPIE}},
    Year = {2015},
    Pages = {95480U-95480U-5},
    Volume = {9548},
    Abstract = {Optical diffraction tomography (ODT) is a tomographic technique that can be used to measure the three-dimensional (3D) refractive index distribution within living cells without the requirement of any marker. In principle, ODT can be regarded as a generalization of optical projection tomography which is equivalent to computerized tomography (CT). Both optical tomographic techniques require projection-phase images of cells measured at multiple angles. However, the reconstruction of the 3D refractive index distribution post-measurement differs for the two techniques. It is known that ODT yields better results than projection tomography, because it takes into account diffraction of the imaging light due to the refractive index structure of the sample. Here, we apply ODT to biological cells in a microfluidic chip which combines optical trapping and microfluidic flow to achieve an optofluidic single-cell rotation. In particular, we address the problem that arises when the trapped cell is not rotating about an axis perpendicular to the imaging plane, but is instead arbitrarily tilted. In this paper we show that the 3D reconstruction can be improved by taking into account such a tilted rotational axis in the reconstruction process.},
    Doi = {10.1117/12.2191501},
    Url = { http://dx.doi.org/10.1117/12.2191501}
    }