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Biomolecular Recognition Based on Field Induced Magnetic Bead Dynamics
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this thesis, three different read-out techniques for biomolecular recognition have been studied. All three techniques rely on the change in dynamic behaviour of probe functionalised magnetic beads after binding to a biomolecular target complementary to the probe.

In the first technique presented, the sample is exposed to an AC magnetic field while the response to this field is probed using a laser source and a photodetector positioned at opposite sides of the sample. Beads bound to the target entity will experience an increase in their hydrodynamic volume, and will not be able to respond as rapidly to an alternating field as free beads. Here, the target entity is either DNA coils formed by rolling circle amplification or biotinylated bovine serum albumin (bBSA). The change in dynamic behaviour is measured as a frequency dependent modulation of transmitted light. Limit of detections (LODs) of 5 pM DNA coils originating from a V. cholerae target and 100 pM of bBSA have been achieved.

In the second technique presented, the beads are magnetically transported across a probe functionalised detection area on a microchip. Beads bound to a target will be blocked from interaction with the detection area probes, whereas in the absence of a target, beads will be immobilised on the detection area. The LOD of biotin for this system proved to be in the range of 20 to 50 ng/ml.

In the third technique presented, the sample is microfluidically transported to a detection area on a microchip. The read-out is performed using a planar Hall effect bridge sensor. A sinusoidal current is applied to the bridge in one direction and the sensor output voltage is measured across the sensor in the perpendicular direction. The AC current induced bead magnetisation contributing to the sensor output will appear different for free beads compared to beads bound to a target. LODs of 500 B. globigii spores and 2 pM of V. cholerae DNA coils were achieved.

From a lab-on-a-chip point of view, all three techniques considered in this thesis show promising results with regards to sensitivity and integrability.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. , 94 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1193
Keyword [en]
Magnetic biosensor, magnetic nanoparticle, DNA detection
National Category
Nano Technology Biochemistry and Molecular Biology Condensed Matter Physics
Research subject
Engineering Science
Identifiers
URN: urn:nbn:se:uu:diva-234302ISBN: 978-91-554-9077-5 (print)OAI: oai:DiVA.org:uu-234302DiVA: diva2:756051
Public defence
2014-12-12, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:15 (English)
Opponent
Supervisors
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council
Available from: 2014-11-21 Created: 2014-10-15 Last updated: 2015-02-03
List of papers
1. Novel readout method for molecular diagnostic assays based on optical measurements of magnetic nanobead dynamics
Open this publication in new window or tab >>Novel readout method for molecular diagnostic assays based on optical measurements of magnetic nanobead dynamics
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2015 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 87, no 3, 1622-1629 p.Article in journal (Refereed) Published
Abstract [en]

We demonstrate detection of DNA coils formed from a Vibrio cholerae DNA target at picomolar concentrations using a novel optomagnetic approach exploiting the dynamic behavior and optical anisotropy of magnetic nanobead (MNB) assemblies. We establish that the complex second harmonic optical transmission spectra of MNB suspensions measured upon application of a weak uniaxial AC magnetic field correlate well with the rotation dynamics of the individual MNBs. Adding a target analyte to the solution leads to the formation of permanent MNB clusters, namely, to the suppression of the dynamic MNB behavior. We prove that the optical transmission spectra are highly sensitive to the formation of permanent MNB clusters and, thereby to the target analyte concentration. As a specific clinically relevant diagnostic case, we detect DNA coils formed via padlock probe recognition and isothermal rolling circle amplification and benchmark against a commercial equipment. The results demonstrate the fast optomagnetic readout of rolling circle products from bacterial DNA utilizing the dynamic properties of MNBs in a miniaturized and low-cost platform requiring only a transparent window in the chip.

National Category
Engineering and Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials; Engineering Science with specialization in Solid State Physics
Identifiers
urn:nbn:se:uu:diva-210686 (URN)10.1021/ac503191v (DOI)000349059000031 ()25539065 (PubMedID)
Funder
Swedish Research Council Formas, 221-2012-444Swedish Research Council Formas, BioBridgesSwedish Research CouncilSwedish Foundation for Strategic Research Knut and Alice Wallenberg Foundation
Available from: 2013-11-13 Created: 2013-11-13 Last updated: 2017-12-06
2. Turn-on optomagnetic bacterial DNA sequence detection using volume-amplified magnetic nanobeads
Open this publication in new window or tab >>Turn-on optomagnetic bacterial DNA sequence detection using volume-amplified magnetic nanobeads
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2015 (English)In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 66, 405-411 p.Article in journal (Refereed) Published
National Category
Other Engineering and Technologies not elsewhere specified
Research subject
Engineering Science with specialization in Solid State Physics; Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-233911 (URN)10.1016/j.bios.2014.11.048 (DOI)000348619800060 ()
Funder
Swedish Research Council Formas, 221-2012-444Carl Tryggers foundation , CTS 12:554Swedish Research Council Formas, 2011-1692Swedish Foundation for Strategic Research
Available from: 2014-10-13 Created: 2014-10-13 Last updated: 2017-12-05Bibliographically approved
3. Optomagnetic bioassay for qualitative biplex detection of bacterial DNA sequences
Open this publication in new window or tab >>Optomagnetic bioassay for qualitative biplex detection of bacterial DNA sequences
2015 (English)In: Biotechnology Journal, ISSN 1860-6768, E-ISSN 1860-7314, Vol. 10, no 3, 469-472 p.Article in journal (Refereed) Published
Abstract [en]

There is an increasing need to develop novel bioassay methods for low-cost, rapid, and easy-to-use multiplex detection of pathogens in various fields ranging from human infectious disease diagnosis, drinking water quality control, to food safety applications. Due to their unique advantages, magnetic and optomagnetic bioassay principles are particularly promising for biodetection platforms that will be used in developing countries. In this paper, an optomagnetic method for rapid and cost-efficient qualitative biplex detection of bacterial DNA sequences is demonstrated. Within less than two hours, the assay gives an answer to whether none, both, or only one of the bacterial DNA sequences is present in the sample. The assay relies on hybridization of oligonucleotide-functionalized magnetic nanobeads of two different sizes to rolling circle amplification (RCA) products originating from two different bacterial targets. The different bead sizes are equipped with different oligonucleotide probes, complementary to only one of the RCA products, and the read-out is carried out in the same sample volume. In an optomagnetic setup, the frequency modulation of transmitted laser light in response to an applied AC magnetic field is measured. The presented methodology is potentially interesting for low-cost screening of pathogens relating to both human and veterinary medicine in resource-poor regions of the world.

National Category
Other Engineering and Technologies not elsewhere specified
Research subject
Engineering Science with specialization in Solid State Physics; Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-233915 (URN)10.1002/biot.201400615 (DOI)000351366600013 ()25512105 (PubMedID)
Funder
Swedish Research Council Formas, 221-2012-444Swedish Research Council Formas, 2011-1692Swedish Foundation for Strategic Research Carl Tryggers foundation , CTS 12:554
Available from: 2014-10-13 Created: 2014-10-13 Last updated: 2017-12-05Bibliographically approved
4. A magnetic transport method for rapid on-chip visual detection of biomolecules
Open this publication in new window or tab >>A magnetic transport method for rapid on-chip visual detection of biomolecules
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(English)Manuscript (preprint) (Other academic)
National Category
Nano Technology Other Physics Topics
Research subject
Engineering Science with specialization in Solid State Physics
Identifiers
urn:nbn:se:uu:diva-234286 (URN)
Available from: 2014-10-15 Created: 2014-10-15 Last updated: 2015-02-03
5. On-Chip Detection of Rolling Circle Amplified DNA Molecules from Bacillus Globigii Spores and Vibrio Cholerae
Open this publication in new window or tab >>On-Chip Detection of Rolling Circle Amplified DNA Molecules from Bacillus Globigii Spores and Vibrio Cholerae
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2014 (English)In: Small, ISSN 1613-6810, E-ISSN 1613-6829, Vol. 10, no 14, 2877-2882 p.Article in journal (Refereed) Published
Abstract [en]

For the first time DNA coils formed by rolling circle amplification are quantified on-chip by Brownian relaxation measurements on magnetic nanobeads using a magnetoresistive sensor. No external magnetic fields are required besides the magnetic field arising from the current through the sensor, which makes the setup very compact. Limits of detection down to 500 Bacillus globigii spores and 2 pM of Vibrio cholerae are demonstrated, which are on the same order of magnitude or lower than those achieved previously using a commercial macro-scale AC susceptometer. The chip-based readout is an important step towards the realization of field tests based on rolling circle amplification molecular analyses.

National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials; Engineering Science with specialization in Solid State Physics
Identifiers
urn:nbn:se:uu:diva-223848 (URN)10.1002/smll.201303325 (DOI)000340660900019 ()24616417 (PubMedID)
Available from: 2014-04-27 Created: 2014-04-27 Last updated: 2017-12-05Bibliographically approved
6. Low-frequency noise in planar Hall effect bridge sensors
Open this publication in new window or tab >>Low-frequency noise in planar Hall effect bridge sensors
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2011 (English)In: Sensors and Actuators A-Physical, ISSN 0924-4247, E-ISSN 1873-3069, Vol. 171, no 2, 212-218 p.Article in journal (Refereed) Published
Abstract [en]

The low-frequency characteristics of planar Hall effect bridge sensors are investigated as function of the sensor bias current and the applied magnetic field. The noise spectra reveal a Johnson-like spectrum at high frequencies, and a 1/f-like excess noise spectrum at lower frequencies, with a knee frequency of around 400 Hz. The 1/f-like excess noise can be described by the phenomenological Hooge equation with a Hooge parameter of γH = 0.016. The detectivity is shown to depend on the total length, width and thickness of the bridge branches. The detectivity is improved by the square root of the length increase. Moreover, the detectivity is shown to depend on the amplitude of the applied magnetic field, revealing a magnetic origin to part of the 1/f noise.

Place, publisher, year, edition, pages
Elsevier, 2011
Keyword
Magnetoresistance, Planar Hall effect, Low-frequency noise, Detectivity
National Category
Materials Engineering
Research subject
Engineering Science with specialization in Microsystems Technology; Engineering Science with specialization in Solid State Physics
Identifiers
urn:nbn:se:uu:diva-163740 (URN)10.1016/j.sna.2011.09.014 (DOI)000297454400022 ()
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council
Available from: 2011-12-19 Created: 2011-12-14 Last updated: 2017-12-08Bibliographically approved
7. Modelling and design of planar Hall effect bridge sensors for low-frequency applications
Open this publication in new window or tab >>Modelling and design of planar Hall effect bridge sensors for low-frequency applications
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2013 (English)In: Sensors and Actuators A-Physical, ISSN 0924-4247, E-ISSN 1873-3069, Vol. 189, 459-465 p.Article in journal (Refereed) Published
Abstract [en]

The applicability of miniaturized magnetic field sensors is being explored in several areas of magneticfield detection due to their integratability, low mass, and potentially low cost. In this respect, differentthin-film technologies, especially those employing magnetoresistance, show great potential, being compatible with batch micro- and nanofabrication techniques. For low-frequency magnetic field detection,sensors based on the planar Hall effect, especially planar Hall effect bridge (PHEB) sensors, show promising performance given their inherent low-field linearity, limited hysteresis and moderate noise figure. Inthis work, the applicability of such PHEB sensors to different areas is investigated. An analytical modelis constructed to estimate the performance of an arbitrary PHEB sensor geometry in terms of, e.g., sensitivity and detectivity. The model is valid for an ideal case, e.g., disregarding shape anisotropy effects, andalso incorporates some approximations. To validate the results, modelled data was compared to measurements on actual PHEBs and was found to predict the measured values within 13% for the investigatedgeometries. Subsequently, the model was used to establish a design process for optimizing a PHEB to aparticular set of requirements on the bandwidth, detectivity, compliance voltage and amplified signalto-noise ratio. By applying this design process, the size, sensitivity, resistance, bias current and powerconsumption of the PHEB can be estimated. The model indicates that PHEBs can be applicable to severaldifferent areas within science including satellite attitude determination and magnetic bead detection inlab-on-a-chip applications, where detectivities down towards 1 nT Hz−0.5at 1 Hz are required, andmaybeeven magnetic field measurements in scientific space missions and archaeological surveying, where thedetectivity has to be less than 100 pT Hz−0.5at 1 Hz.

Keyword
Magnetoresistance Planar Hall effect Low-frequency noise Detectivity
National Category
Other Engineering and Technologies not elsewhere specified
Research subject
Engineering Science with specialization in Solid State Physics; Engineering Science with specialization in Materials Science; Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-188200 (URN)10.1016/j.sna.2012.10.037 (DOI)000314622600055 ()
Available from: 2012-12-14 Created: 2012-12-13 Last updated: 2017-12-06Bibliographically approved

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  • modern-language-association-8th-edition
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