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Publications (10 of 32) Show all publications
Guldevall, K., Brandt, L., Forslund, E., Olofsson, K., Frisk, T. W., Olofsson, P. E., . . . Önfelt, B. (2016). Microchip screening Platform for single cell assessment of NK cell cytotoxicity. Frontiers in Immunology, 7, Article ID 119.
Open this publication in new window or tab >>Microchip screening Platform for single cell assessment of NK cell cytotoxicity
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2016 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 7, article id 119Article in journal (Refereed) Published
Abstract [en]

Here, we report a screening platform for assessment of the cytotoxic potential of individual natural killer (NK) cells within larger populations. Human primary NK cells were distributed across a silicon-glass microchip containing 32,400 individual microwells loaded with target cells. Through fluorescence screening and automated image analysis, the numbers of NK and live or dead target cells in each well could be assessed at different time points after initial mixing. Cytotoxicity was also studied by time-lapse live-cell imaging in microwells quantifying the killing potential of individual NK cells. Although most resting NK cells (approximate to 75%) were non-cytotoxic against the leukemia cell line K562, some NK cells were able to kill several (>= 3) target cells within the 12-h long experiment. In addition, the screening approach was adapted to increase the chance to find and evaluate serial killing NK cells. Even if the cytotoxic potential varied between donors, it was evident that a small fraction of highly cytotoxic NK cells were responsible for a substantial portion of the killing. We demonstrate multiple assays where our platform can be used to enumerate and characterize cytotoxic cells, such as NK or T cells. This approach could find use in clinical applications, e.g., in the selection of donors for stem cell transplantation or generation of highly specific and cytotoxic cells for adoptive immunotherapy.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2016
Keywords
NK cells, cytotoxicity, single cell analysis, microchip, screening, microscopy, fluorescence, immune synapse
National Category
Immunology
Identifiers
urn:nbn:se:kth:diva-185604 (URN)10.3389/fimmu.2016.00119 (DOI)000373340600001 ()2-s2.0-84966702164 (Scopus ID)
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Swedish Childhood Cancer FoundationSwedish Cancer Society
Note

QC 20160428

Available from: 2016-04-28 Created: 2016-04-25 Last updated: 2017-11-30Bibliographically approved
Xu, H., Li, L., Manneberg, O., Russom, A., Gylfason, K. B., Brismar, H. & Fu, Y. (2013). Modulated fluorescence of colloidal quantum dots embedded in a porous alumina membrane. Journal of Physical Chemistry B, 177(45), 14151-14156
Open this publication in new window or tab >>Modulated fluorescence of colloidal quantum dots embedded in a porous alumina membrane
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2013 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 177, no 45, p. 14151-14156Article in journal (Refereed) Published
Abstract [en]

The fluorescence spectrum of CdSe core-CdS/ZnS shell colloidal quantum dots (QDs) embedded in porous alumina membrane was studied. Small peaks, superimposed on the principal QD fluorescence spectrum, were observed. Finite-difference time-domain simulation indicates that the QD point radiation emitting from within the membrane is strongly modulated by the photonic band structure introduced by the membrane pores, leading to the observed fine spectral features. Moreover, the principal QD fluorescence peak red-shifted when the optical excitation power was increased, which is attributed to QD material heating due to emitted phonons when the photoexcited electron and hole relax nonradiatively from high-energy states to the ground exciton state before fluorescence.

Keywords
Colloidal quantum dots, Finite difference time domain simulations, Fluorescence peak, Fluorescence spectra, Photoexcited electrons, Photonic band structures, Porous alumina membranes, Spectral feature
National Category
Physical Chemistry
Identifiers
urn:nbn:se:kth:diva-136255 (URN)10.1021/jp409132e (DOI)000327111200024 ()2-s2.0-84887899102 (Scopus ID)
Funder
Swedish Research Council, 621-2011-4381 B0460801Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20131217

Available from: 2013-12-04 Created: 2013-12-04 Last updated: 2017-12-06Bibliographically approved
Grondin, Y., Cotanche, D. A., Manneberg, O., Molina, R., Treviño-Villarreal, J. H., Sepulveda, R., . . . Rogers, R. A. (2013). Pulmonary delivery of d-methionine is associated with an increase in ALCAR and glutathione in cochlear fluids.. Hearing Research, 298, 93-103
Open this publication in new window or tab >>Pulmonary delivery of d-methionine is associated with an increase in ALCAR and glutathione in cochlear fluids.
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2013 (English)In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 298, p. 93-103Article in journal (Refereed) Published
Abstract [en]

In animals, hearing loss resulting from cochlear mechanosensory cell damage can be mitigated by antioxidants such as d-methionine (d-met) and acetyl-l-carnitine (ALCAR). The systemic routes of administration of these compounds, that must of necessity transit trough the cochlear fluids, may affect the antioxidant levels in the cochlea and the resulting oto-protective effect. In this study, we analyzed the pharmacokinetics of [C]d-met in the cochlea and four other tissues after intratracheal (IT), intranasal (IN), and oral by gavage (OG) administration and compared it to intravenous administration (IV). We then analyzed the effect of these four routes on the antioxidant content of the cochlear fluids after d-met or ALCAR administration, by liquid chromatography/mass spectrometry. Our results showed that the concentration of methionine and ALCAR in cochlear fluids significantly increased after their respective systemic administration. Interestingly, d-met administration also contributed to an increase of ALCAR. Our results also showed that the delivery routes differently affected the bioavailability of administered [C]d-met as well as the concentrations of methionine, ALCAR and the ratio of oxidized to reduced glutathione. Overall, pulmonary delivery via IT administration achieved high concentrations of methionine, ALCAR, and oxidative-related metabolites in cochlear fluids, in some cases surpassing IV administration, while IN route appeared to be the least efficacious. To our knowledge, this is the first report of the direct measurements of antioxidant levels in cochlear fluids after their systemic administration. This report also demonstrates the validity of the pulmonary administration of antioxidants and highlights the different contributions of d-met and ALCAR allowing to further investigate their impact on oxidative stress in the cochlear microenvironment.

National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:kth:diva-119785 (URN)10.1016/j.heares.2012.12.011 (DOI)000317159100010 ()23296212 (PubMedID)
Note

QC 20130603

Available from: 2013-03-22 Created: 2013-03-22 Last updated: 2018-01-11Bibliographically approved
Treviño-Villareal, J. H., Cotanche, D. A., Sepúlveda, R., Bortoni, M. E., Manneberg, O., Udagawa, T. & Rogers, R. A. (2011). Host-derived pericytes and Sca-1+ cells predominate in the MART-1− stroma fraction of experimentally induced melanoma. Journal of Histochemistry and Cytochemistry, 59, 1060-1075
Open this publication in new window or tab >>Host-derived pericytes and Sca-1+ cells predominate in the MART-1 stroma fraction of experimentally induced melanoma
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2011 (English)In: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 59, p. 1060-1075Article in journal (Refereed) Published
Abstract [en]

Identification of cell types in tumor-associated stroma that are involved in the development of melanoma is hampered by their heterogeneity. The authors used flow cytometry and immunohistochemistry to demonstrate that anti-MART-1 antibodies can discriminate between melanoma and stroma cells. They investigated the cellular composition of the MART-1-, non-hematopoietic melanoma-associated stroma, finding it consisted mainly of Sca-1+ and CD146+ cells. These cell types were also observed in the skin and muscle adjacent to developing melanomas. The Sca-1+ cell population was observed distributed in the epidermis, hair follicle bulges, and tumor capsule. The CD146+ population was found distributed within the tumor, mainly associated with blood vessels in a perivascular location. In addition to a perivascular distribution, CD146+ cells expressed α-smooth muscle actin, lacked expression of endothelial markers CD31 and CD34, and were therefore identified as pericytes. Pericytes were found to be associated with CD31+ endothelial cells; however, some pericytes were also observed associated with CD31-, MART-1+ B16 melanoma cells that appeared to form blood vessel structures. Furthermore, the authors observed extensive nuclear expression of HIF-1α in melanoma and stroma cells, suggesting hypoxia is an important factor associated with the melanoma microenvironment and vascularization. The results suggest that pericytes and Sca-1+ stroma cells are important contributors to melanoma development.

Keywords
MART-1, Sca-1, CD146, pericytes, melanoma, tumor-associated stroma
National Category
Cell and Molecular Biology Cancer and Oncology
Identifiers
urn:nbn:se:kth:diva-179191 (URN)10.1369/0022155411428078 (DOI)000297649800002 ()3283083 (PubMedID)2-s2.0-84856012298 (Scopus ID)
Note

QC 20160226

Available from: 2015-12-11 Created: 2015-12-11 Last updated: 2018-01-10Bibliographically approved
Guldevall, K., Frisk, T., Vanherberghen, B., Khorsidi, M. A., Manneberg, O., Christakou, A., . . . Önfelt, B. (2010). Imaging immune surveillance by individual Natural Killer cells isolated in arrays of nanoliter wells. Paper presented at 12th Meeting of the Society for Natural Immunity, NK2010. Cavtat-Dubrovnik, Croatia. April 20-24, 2010.
Open this publication in new window or tab >>Imaging immune surveillance by individual Natural Killer cells isolated in arrays of nanoliter wells
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2010 (English)Conference paper, Published paper (Refereed)
National Category
Cell Biology Immunology
Identifiers
urn:nbn:se:kth:diva-90431 (URN)
Conference
12th Meeting of the Society for Natural Immunity, NK2010. Cavtat-Dubrovnik, Croatia. April 20-24, 2010
Note
QC 20120418Available from: 2012-02-23 Created: 2012-02-23 Last updated: 2012-04-18Bibliographically approved
Vanherberghen, B., Manneberg, O., Christakou, A., Frisk, T., Ohlin, M., Hertz, H. M., . . . Wiklund, M. (2010). Ultrasound-controlled cell aggregation in a multi-well chip. Lab on a Chip, 10(20), 2727-2732
Open this publication in new window or tab >>Ultrasound-controlled cell aggregation in a multi-well chip
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2010 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 10, no 20, p. 2727-2732Article in journal (Refereed) Published
Abstract [en]

We demonstrate a microplate platform for parallelized manipulation of particles or cells by frequency-modulated ultrasound. The device, consisting of a silicon-glass microchip and a single ultrasonic transducer, enables aggregation, positioning and high-resolution microscopy of cells distributed in an array of 100 microwells centered on the microchip. We characterize the system in terms of temperature control, aggregation and positioning efficiency, and cell viability. We use time-lapse imaging to show that cells continuously exposed to ultrasound are able to divide and remain viable for at least 12 hours inside the device. Thus, the device can be used to induce and maintain aggregation in a parallelized fashion, facilitating long-term microscopy studies of, e.g., cell-cell interactions.

Keywords
article, cell interaction, cell viability, device, human, human cell, microchip analysis, microscopy, priority journal, thermoregulation, ultrasound, ultrasound transducer
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-26656 (URN)10.1039/c004707d (DOI)000282314200012 ()2-s2.0-77957655329 (Scopus ID)
Note
QC 20101203Available from: 2010-12-03 Created: 2010-11-26 Last updated: 2018-01-12Bibliographically approved
Ohlin, M., Manneberg, O. & Wiklund, M. (2009). Characterization of acoustic streaming in an ultrasonic cage. Paper presented at 7th USWNet Meeting: Unidirectional motion produced by vibrating fields for cell/particle and fluid control. Stockholm, Sweden. Nov. 30th - Dec. 1st, 2009.
Open this publication in new window or tab >>Characterization of acoustic streaming in an ultrasonic cage
2009 (English)Conference paper, Poster (with or without abstract) (Other academic)
National Category
Other Physics Topics
Identifiers
urn:nbn:se:kth:diva-90430 (URN)
Conference
7th USWNet Meeting: Unidirectional motion produced by vibrating fields for cell/particle and fluid control. Stockholm, Sweden. Nov. 30th - Dec. 1st, 2009
Note
QC 20120426Available from: 2012-02-23 Created: 2012-02-23 Last updated: 2012-04-26Bibliographically approved
Manneberg, O., Vanherberghen, B., Önfelt, B. & Wiklund, M. (2009). Flow-free transport of cells in microchannels by frequency-modulated ultrasound. Lab on a Chip, 9, 833-837
Open this publication in new window or tab >>Flow-free transport of cells in microchannels by frequency-modulated ultrasound
2009 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 9, p. 833-837Article in journal (Refereed) Published
Abstract [en]

We demonstrate flow-free transport of cells and particles by the use of frequency-modulated ultrasonic actuation of a microfluidic chip. Two different modulation schemes are combined: A rapid (1 kHz) linear frequency sweep around similar to 6.9 MHz is used for two-dimensional spatial stabilization of the force field over a 5 mm long inlet channel of constant cross section, and a slow (0.2-0.7 Hz) linear frequency sweep around similar to 2.6 MHz is used for flow-free ultrasonic transport and positioning of cells or particles. The method is used for controlling the motion and position of cells monitored with high-resolution optical microscopy, but can also be used more generally for improving the robustness and performance of ultrasonic manipulation micro-devices.

Keywords
manipulation; particles; chip; separation; channels
National Category
Condensed Matter Physics
Identifiers
urn:nbn:se:kth:diva-10918 (URN)10.1039/B816675G (DOI)000263847000012 ()2-s2.0-61849133822 (Scopus ID)
Note
QC 20100730Available from: 2009-08-18 Created: 2009-08-18 Last updated: 2017-12-13Bibliographically approved
Vanherberghen, B., Manneberg, O., Christakou, A., Frisk, T., Önfelt, B. & Wiklund, M. (2009). Highly parallelized cell aggregation by ultrasound for studies of immune cell interaction. Paper presented at 7th USWNet Meeting: Unidirectional motion produced by vibrating fields for cell/particle and fluid control. Stockholm, Sweden. Nov. 30th - Dec. 1st, 2009.
Open this publication in new window or tab >>Highly parallelized cell aggregation by ultrasound for studies of immune cell interaction
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2009 (English)Conference paper, Published paper (Other academic)
National Category
Other Physics Topics
Identifiers
urn:nbn:se:kth:diva-90428 (URN)
Conference
7th USWNet Meeting: Unidirectional motion produced by vibrating fields for cell/particle and fluid control. Stockholm, Sweden. Nov. 30th - Dec. 1st, 2009
Note
QC 20120417Available from: 2012-02-23 Created: 2012-02-23 Last updated: 2012-04-17Bibliographically approved
Manneberg, O. (2009). Multidimensional Ultrasonic Standing Wave Manipulation in Microfluidic Chips. (Doctoral dissertation). Stockholm: KTH
Open this publication in new window or tab >>Multidimensional Ultrasonic Standing Wave Manipulation in Microfluidic Chips
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The use of ultrasonic standing waves for contactless manipulation of microparticles in microfluidic systems is a field with potential to become a new standard tool in lab-on-chip systems. Compared to other contactless manipulation methods ultrasonic standing wave manipulation shows promises of gentle cell handling, low cost, and precise temperature control. The technology can be used both for batch handling, such as sorting and aggregation, and handling of single particles.

This doctoral Thesis presents multi-dimensional ultrasonic manipulation, i.e., manipulation in both two and three spatial dimensions as well as time-dependent manipulation of living cells and microbeads in microfluidic systems. The lab-on-chip structures used allow for high-quality optical microscopy, which is central to many bio-applications. It is demonstrated how the ultrasonic force fields can be spatially confined to predefined regions in the system, enabling sequential manipulation functions. Furthermore, it is shown how frequency-modulated signals can be used both for spatial stabilization of the force fields as well as for flow-free transport of particles in a microchannel. Design parameters of the chip-transducer systems employed are investigated experimentally as well as by numerical simulations. It is shown that three-dimensional resonances in the solid structure of the chip strongly influences the resonance shaping in the channel.

Place, publisher, year, edition, pages
Stockholm: KTH, 2009. p. ix, 83
Series
Trita-FYS, ISSN 0280-316X ; 2009:44
National Category
Condensed Matter Physics
Identifiers
urn:nbn:se:kth:diva-10919 (URN)978-91-7415-398-9 (ISBN)
Public defence
2009-09-11, FD5, Roslagstullsbacken 21, Stockholm, 14:00 (English)
Opponent
Supervisors
Note
QC 20100730Available from: 2009-09-01 Created: 2009-08-18 Last updated: 2010-07-30Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-4720-2756

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