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Publications (10 of 34) Show all publications
Prager, I., Liesche, C., van Ooijen, H., Urlaub, D., Verron, Q., Sandström, N., . . . Watzl, C. (2019). NK cells switch from granzyme B to death receptor–mediated cytotoxicity during serial killing. Journal of Experimental Medicine, 7(9), 2113-2127
Open this publication in new window or tab >>NK cells switch from granzyme B to death receptor–mediated cytotoxicity during serial killing
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2019 (English)In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 7, no 9, p. 2113-2127Article in journal (Refereed) Published
Abstract [en]

NK cells eliminate virus-infected and tumor cells by releasing cytotoxic granules containing granzyme B (GrzB) or by engaging death receptors that initiate caspase cascades. The orchestrated interplay between both cell death pathways remains poorly defined. Here we simultaneously measure the activities of GrzB and caspase-8 in tumor cells upon contact with human NK cells. We observed that NK cells switch from inducing a fast GrzB-mediated cell death in their first killing events to a slow death receptor–mediated killing during subsequent tumor cell encounters. Target cell contact reduced intracellular GrzB and perforin and increased surface-CD95L in NK cells over time, showing how the switch in cytotoxicity pathways is controlled. Without perforin, NK cells were unable to perform GrzB-mediated serial killing and only killed once via death receptors. In contrast, the absence of CD95 on tumor targets did not impair GrzB-mediated serial killing. This demonstrates that GrzB and death receptor–mediated cytotoxicity are differentially regulated during NK cell serial killing.

National Category
Immunology in the medical area
Identifiers
urn:nbn:se:kth:diva-256334 (URN)10.1084/jem.20181454 (DOI)000484027100013 ()31270246 (PubMedID)2-s2.0-85071782240 (Scopus ID)
Note

QC 20190822

Available from: 2019-08-22 Created: 2019-08-22 Last updated: 2019-10-28Bibliographically approved
da Silva Granja, C., Sandström, N., Efimov, I., Ostanin, V., van der Wijngaart, W., Klenerman, D. & Ghosh, S. (2018). Characterisation of particle-surface interactions via anharmonic acoustic transduction. Sensors and actuators. B, Chemical, 272, 175-184
Open this publication in new window or tab >>Characterisation of particle-surface interactions via anharmonic acoustic transduction
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2018 (English)In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 272, p. 175-184Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Nano Technology
Identifiers
urn:nbn:se:kth:diva-235182 (URN)10.1016/j.snb.2018.05.016 (DOI)000439715000023 ()2-s2.0-85048499666 (Scopus ID)
Projects
Norosensor
Note

QC 20181003

Available from: 2018-09-17 Created: 2018-09-17 Last updated: 2019-04-12Bibliographically approved
Guha, A., Sandström, N., Ostanin, V., van der Wijngaart, W., Klenerman, D. & Ghosh, S. (2018). Simple and ultrafast resonance frequency and dissipation shift measurements using a fixed frequency drive. Sensors and actuators. B, Chemical, 281, 960-970
Open this publication in new window or tab >>Simple and ultrafast resonance frequency and dissipation shift measurements using a fixed frequency drive
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2018 (English)In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 281, p. 960-970Article in journal (Refereed) Published
Abstract [en]

A new method for determination of resonance frequency and dissipation of a mechanical oscillator is presented. Analytical expressions derived using the Butterworth-Van Dyke equivalent electrical circuit allow the determination of resonance frequency and dissipation directly from each impedance datapoint acquired at a fixed amplitude and frequency of drive, with no need for numerical fitting or measurement dead time unlike the conventional impedance or ring-down analysis methods. This enables an ultrahigh time resolution and superior noise performance with relatively simple instrumentation. Quantitative validations were carried out successfully against the impedance analysis method for inertial and viscous loading experiments on a 14.3 MHz quartz crystal resonator (QCR). Resonance frequency shifts associated with the transient processes of quick needle touches on a thiol self-assembled-monolayer functionalised QCR in liquid were measured with a time resolution of 112 μs, which is nearly two orders of magnitude better than the fastest reported quartz crystal microbalance. This simple and fast fixed frequency drive (FFD) based method for determination of resonance frequency and dissipation is potentially more easily multiplexable and implementable on a single silicon chip delivering economies of scale.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
QCM NOROSENSOR
National Category
Engineering and Technology
Identifiers
urn:nbn:se:kth:diva-239430 (URN)10.1016/j.snb.2018.11.052 (DOI)000455021500118 ()2-s2.0-85056834731 (Scopus ID)
Note

QC 20181129

Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2019-04-12Bibliographically approved
Guha, A., Sandström, N., Ostanin, V., van der Wijngaart, W., Klenerman, D. & Ghosh, S. (2017). Measurement of protein binding with vastly improved time resolution using a quartz crystal microbalance driven at a fixed frequency. In: : . Paper presented at 5th International conference on Bio-Sensing Technology, 7 - 10 May 2017, Riva Del Garda, Italy.
Open this publication in new window or tab >>Measurement of protein binding with vastly improved time resolution using a quartz crystal microbalance driven at a fixed frequency
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2017 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

Introduction: Quartz crystal microbalance (QCM) is commonly used to study biomolecular binding by measuring shifts in resonance frequency of a quartz-crystal-oscillator. However, the currently used methods like impedance analysis or QCM-D, which require repeated sweeps or ringing, are limited in time resolution (~1 second) due to the need for averaging. This restricts our ability to study transient biomolecular processes, which occur in sub-millisecond time scale. A novel technique has been reported here that allows quantification of resonance frequency of a quartz-crystal-oscillator with significantly improved time resolution by driving and measuring continuously at a constant frequency within the resonance bandwidth. 

Method: The reactive component of the experimentally obtained impedance is utilized for the estimation of resonance frequency from the Butterworth Van-dyke (BVD) model of a quartz-crystal-oscillator, assuming that changes in motional inductance and capacitance around resonance are negligible. Triplicate sets of experiments involving the binding of streptavidin with a biotin functionalized 14.3 MHz quartz oscillator surface were performed. Intermittent frequency sweeps and fixed frequency drives, both of 0.1 second duration and around 14.3 MHz, were taken at intervals of 2 minutes under the flow of phosphate-buffer-saline (PBS buffer) before and after injection of streptavidin. 

Results: The average shift in resonance frequency from the baseline (measurements before streptavidin injection) due to streptavidin-biotin binding, calculated from the fixed frequency drive or FFD (148 Hz) was within 1% of that estimated from the frequency sweep method by fitting the experimentally recorded impedance employing the BVD model (149 Hz). 

Discussion: The agreement of the FFD with conventional frequency sweep method suggests that protein binding can be quantified with reasonable accuracy from each impedance data point, which with our set-up is recorded at 30 kHz sampling rate. This gives a time resolution of 0.03 millisecond, which is about 4 orders of magnitude improvement over the state-of-the-art.

National Category
Medical Engineering
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-249535 (URN)
Conference
5th International conference on Bio-Sensing Technology, 7 - 10 May 2017, Riva Del Garda, Italy
Note

QC 20190522

Available from: 2019-04-12 Created: 2019-04-12 Last updated: 2019-05-22Bibliographically approved
Pardon, G., Ladhani, L., Sandström, N., Ettori, M., Lobov, G. & van der Wijngaart, W. (2015). Aerosol sampling using an electrostatic precipitator integrated with a microfluidic interface. Sensors and actuators. B, Chemical, 212, 344-352
Open this publication in new window or tab >>Aerosol sampling using an electrostatic precipitator integrated with a microfluidic interface
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2015 (English)In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 212, p. 344-352Article in journal (Refereed) Published
Abstract [en]

In this work, the development of a point-of-care (PoC) system to capture aerosol from litres of air directly onto a microfluidic lab-on-chip for subsequent analysis is addressed. The system involves an electrostatic precipitator that uses corona charging and electrophoretic transport to capture aerosol droplets onto a microfluidic air-to-liquid interface for downstream analysis. A theoretical study of the governing geometric and operational parameters for optimal electrostatic precipitation is presented. The fabrication of an electrostatic precipitator prototype and its experimental validation using a laboratory-generated aerosolized dye is described. Collection efficiencies were comparable to those of a state-of-the-art Biosampler impinger, with the significant advantage of providing samples that are at least 10 times more concentrated. Finally, we discuss the potential of such a system for breath-based diagnostics.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
breath analysis, poc, point-of-care, lab-on-chip, loc, microfluidics, aerosol, sampling, medical device, diagnostics, electrostatic precipitation, corona discharge
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering Other Medical Biotechnology
Research subject
Electrical Engineering
Identifiers
urn:nbn:se:kth:diva-144986 (URN)10.1016/j.snb.2015.02.008 (DOI)000351017700043 ()2-s2.0-84923763722 (Scopus ID)
Projects
Rappid
Note

QC 20150223

Available from: 2014-05-05 Created: 2014-05-05 Last updated: 2018-04-29Bibliographically approved
Sandström, N. (2015). Integrating Biosensors for Air Monitoring and Breath-Based Diagnostics. (Doctoral dissertation). Stockholm: KTH Royal Institute of Technology
Open this publication in new window or tab >>Integrating Biosensors for Air Monitoring and Breath-Based Diagnostics
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The air we breathe is the concern of all of us but nevertheless we only know very little about airborne particles, and especially which biological microorganisms they contain. Today, we live in densely populated societies with a growing number of people, making us particularly vulnerable to air transmission of pathogens. With the recent appearance of highly pathogenic types of avian influenza in southeast Asia and the seasonal outbreaks of gastroenteritis caused by the extremely contagious norovirus, the need for portable, sensitive and rapid instruments for on-site detection and monitoring of airborne pathogens is apparent.

Unfortunately, the integration incompatibility between state-of-the-art air sampling techniques and laboratory based analysis methods makes instruments for in-the-field rapid detection of airborne particles an unresolved challenge.

This thesis aims at addressing this challenge by the development of novel manufacturing, integration and sampling techniques to enable the use of label-free biosensors for rapid and sensitive analysis of airborne particles at the point-of-care or in the field.

The first part of the thesis introduces a novel reaction injection molding technique for the fabrication of high quality microfluidic cartridges. In addition, electrically controlled liquid aspiration and dispensing is presented, based on the use of a thermally actuated polymer composite integrated with microfluidic cartridges.

The second part of the thesis demonstrates three different approaches of biosensor integration with microfluidic cartridges, with a focus on simplifying the design and integration to enable disposable use of the cartridges.

The third part to the thesis presents a novel air sampling technique based on electrophoretic transport of airborne particles directly to microfluidic cartridges. This technique is enabled by the development of a novel microstructured component for integrated air-liquid interfacing. In addition, a method for liquid sample mixing with magnetic microbeads prior to downstream biosensing is demonstrated.In the fourth part of the thesis, three different applications for airborne particle biosensing are introduced and preliminary experimental results are presented.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2015. p. xix, 85
Series
TRITA-EE, ISSN 1653-5146 ; 2015:020
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:kth:diva-165454 (URN)978-91-7595-560-5 (ISBN)
Public defence
2015-05-22, Q2, Osquldas väg 10, KTH, Stockholm, 10:00 (English)
Opponent
Supervisors
Projects
RPARappidNorosensor
Funder
EU, FP7, Seventh Framework ProgrammeVINNOVASwedish Research CouncilSwedish Foundation for Strategic Research
Note

QC 20150429

Available from: 2015-04-29 Created: 2015-04-28 Last updated: 2015-04-29Bibliographically approved
Gylfason, K. B., Errando-Herranz, C., Sandström, N., Shafagh, R. Z., Wijngaart, W. v. & Haraldsson, T. (2015). Integration of polymer based microfluidics with silicon photonics for biosensing applications. In: : . Paper presented at The 2015 E-MRS Fall Meeting and Exhibit, Warsaw, Poland..
Open this publication in new window or tab >>Integration of polymer based microfluidics with silicon photonics for biosensing applications
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2015 (English)Conference paper, Oral presentation only (Other academic)
Abstract [en]

We present a novel integration method for packaging silicon photonic sensors with polymer microfluidics, designed to be suitable for wafer-level production. The method addresses the previously unmet manufacturing challenges of matching the microfluidic footprint area to that of the photonics, and of robust bonding of microfluidic layers to biofunctionalized surfaces. We demonstrate the fabrication, in a single step, of a microfluidic layer in the recently introduced OSTE polymer, and the subsequent unassisted dry bonding of the microfluidic layer to a grating coupled silicon photonic ring resonator sensor chip. The microfluidic layer features photopatterned through holes (vias) for optical fiber probing and fluid connections, as well as molded microchannels and tube connectors, and is manufactured and subsequently bonded to a silicon sensor chip in less than 10 minutes. Combining this new microfluidic packaging method with photonic waveguide surface gratings for light couplin g allows matching the size scale of microfluidics to that of current silicon photonic biosensors.

National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-173865 (URN)
Conference
The 2015 E-MRS Fall Meeting and Exhibit, Warsaw, Poland.
Projects
CellRingVR-HETXMEMS
Funder
Swedish Research Council, B0460801EU, European Research Council, 267528Swedish Research Council, 621-2012-5364
Note

QC 20150928

Available from: 2015-09-21 Created: 2015-09-21 Last updated: 2015-09-28Bibliographically approved
Sandström, N., Zandi Shafagh, R., Vastesson, A., Carlborg, F., van der Wijngaart, W. & Haraldsson, T. (2015). Reaction injection molding and direct covalent bonding of OSTE+ polymer microfluidic devices. Journal of Micromechanics and Microengineering, 25(7)
Open this publication in new window or tab >>Reaction injection molding and direct covalent bonding of OSTE+ polymer microfluidic devices
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2015 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 25, no 7Article in journal (Refereed) Published
Abstract [en]

In this article, we present OSTE+RIM, a novel reaction injection molding (RIM) process that combines the merits of off-stoichiometric thiol–ene epoxy (OSTE+) thermosetting polymers with the fabrication of high quality microstructured parts. The process relies on the dual polymerization reactions of OSTE+ polymers, where the first curing step is used in OSTE+RIM for molding intermediately polymerized parts with well-defined shapes and reactive surface chemistries. In the facile back-end processing, the replicated parts are directly and covalently bonded and become fully polymerized using the second curing step, generating complete microfluidic devices. To achieve unprecedented rapid processing, high replication fidelity and low residual stress, OSTE+RIM uniquely incorporates temperature stabilization and shrinkage compensation of the OSTE+ polymerization during molding. Two different OSTE+ formulations were characterized and used for the OSTE+RIM fabrication of optically transparent, warp-free and natively hydrophilic microscopy glass slide format microfluidic demonstrator devices, featuring a storage modulus of 2.3 GPa and tolerating pressures of at least 4 bars. 

Place, publisher, year, edition, pages
Institute of Physics (IOP), 2015
Keywords
off-stoichiometric thiol–ene, epoxy, OSTE+, reaction injection molding, device fabrication, polymers, microfluidics
National Category
Nano Technology
Identifiers
urn:nbn:se:kth:diva-165616 (URN)10.1088/0960-1317/25/7/075002 (DOI)000356896100013 ()2-s2.0-84937422492 (Scopus ID)
Note

QC 201500618

Available from: 2015-04-29 Created: 2015-04-29 Last updated: 2019-09-20Bibliographically approved
Zhou, X., Carlborg, C. F., Sandström, N., Vastesson, A., Saharil, F., van der Wijngaart, W. & Haraldsson, T. (2014). OSTE+ microfluidic devices with lithographically defined hydrophobic/ hydrophilic patterns and biocompatible chip sealing: OSTEmer Allows Easy Fabrication of Microfluidic Chips. In: DIATECH 2014: . Paper presented at DIATECH 2014, Leuven, Belgium (pp. 26-27).
Open this publication in new window or tab >>OSTE+ microfluidic devices with lithographically defined hydrophobic/ hydrophilic patterns and biocompatible chip sealing: OSTEmer Allows Easy Fabrication of Microfluidic Chips
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2014 (English)In: DIATECH 2014, 2014, p. 26-27Conference paper, Oral presentation with published abstract (Refereed)
Keywords
OSTE+, surface modification, microfabrication, microfluidics, theracage
National Category
Engineering and Technology Medical and Health Sciences
Identifiers
urn:nbn:se:kth:diva-155514 (URN)
Conference
DIATECH 2014, Leuven, Belgium
Projects
Theracage
Note

QC 20150302

Available from: 2014-11-06 Created: 2014-11-06 Last updated: 2017-11-22Bibliographically approved
Leirs, K., Sandström, N., Ladhani, L., Spasic, D., Ostanin, V., Klenerman, D., . . . Ghosh, S. (2014). Rapid ultra-sensitive detection of influenza A nucleoproteins using a microfluidic nonlinear acoustic sensor. In: : . Paper presented at Biosensors 2014; Melbourne, Australia, 27–30 May 2014. Elsevier
Open this publication in new window or tab >>Rapid ultra-sensitive detection of influenza A nucleoproteins using a microfluidic nonlinear acoustic sensor
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2014 (English)Conference paper, Poster (with or without abstract) (Refereed)
Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
biosensor, lab-on-chip, point-of-care, microfluidics, adt, Rappid
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:kth:diva-159310 (URN)
Conference
Biosensors 2014; Melbourne, Australia, 27–30 May 2014
Projects
Rappid
Note

QC 20150401. QC 20160212

Available from: 2015-01-29 Created: 2015-01-29 Last updated: 2016-02-12Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-6443-878X

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