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Optical devices and methods for distributed lab-on-a-chip analyses
Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lab-on-a-chip (LOC) technologies entail the miniaturization of analytical systems, and the reduction of required sample and reagent volumes. LOC devices offer compact alternatives to classical instrumentation while delivering comparable performance and disposable formats. These aspects make disposable LOC a clear candidate to support distributed chemical sensing applications; however, the need of accessory services and readout obstructs the materialization of pervasively distributed LOC solutions.

In this thesis methods and devices to solve this problem are investigated. A distinctive aspect of this work is the pursuit of solutions based on disposable LOC elements specifically conceived to exploit ubiquitous infrastructure for readout and evaluation.

Consumer electronic devices, such as cell phones are ubiquitous platforms with residual capabilities that can be used for chemical sensing, if properly interfaced. This work investigates elements and tools needed to empower cell phones as readers of disposable LOC devices and commercial disposable tests.

Access to flexible fabrication of LOC devices at low cost is an important requisite for testing ideas and implementing customized solutions. A first contribution in this thesis is the development of a platform for mask less fabrication of 3D microstructures, which coexists on a routine fluorescence microscope. This microscope projection lithography system (MPLS) is capable of controlled 3D micro structuring, including cavities and cantilever geometries, and the sealing of monolithic micro cavities to glass substrates as well as the connection to large scale service areas. This fabrication platform and other fabrication methods were used along this thesis to provide disposable optical and fluidic components.

Besides custom-made LOC solutions there are well-established commercial disposable devices, which are essentially compatible with decentralized diagnosis, except for the use of specialized readers that confine them to medical centers. The implementation of high dynamic range (HDR) imaging with standard cell phones, using the phone screen to control exposure, shows that sensitivity and resolution can be boosted to permit robust evaluation of this type of disposable tests, in decentralized scenarios.

Solutions employing commercial tests, which have not been designed for cell phone evaluation, are typically suboptimal and the investigation of customized LOC components occupies a central role in this thesis. Accordingly, one important aspect to evaluate LOC devices in compact configurations is to be able to image the LOC at a close distance from the phone camera, a condition for which phones cameras are not able to focus.

In addition, different phone brands and models have different optical specifications, and a practical refocusing solution should adapt to all of them. In this work an adaptive lens concept, complemented by phone time-lapse acquisition, which can be integrated in disposable LOCs, is demonstrated.

The implementation of sensitive detection methods, such as surface plasmon resonance (SPR), which is compatible with label free protocols that simplify sample conditioning, is central to the materialization of ubiquitous LOCs readable with cell phones. In this thesis a disposable optical coupler, conditioning illumination taken from the phone screen, is used to create an angle resolved SPR signal from a LOC, which is read with the phone front camera. Tested performance is comparable with commercial compact SPR modules and detection of β2 microglobulin, which is an established marker for cancer, inflammatory disorders, and kidney disease, is within the diagnostics range for blood and urine.

Finally, fluorescence detection within classical LOC devices is tailored to be detectable with consumer cameras. In this case a disposable optical coupler and fluidics is designed to condition laser illumination into total internal reflection excitation, while DSLR and phone cameras capture optically separated fluorescence. The system configuration supports a broad dynamic range and HDR imaging enables localized resolution boost at selected detection ranges. Detection of free fucose, a diagnostic marker for liver cirrhosis and several cancer forms, is shown feasible with a HDR implementation, as one last example of practical LOC detection schemes for decentralized scenarios.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. , 54 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1492
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:liu:diva-86183ISBN: 978-91-7519-732-6 (print)OAI: oai:DiVA.org:liu-86183DiVA: diva2:575458
Public defence
2013-02-08, Plank, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 10:15 (English)
Opponent
Supervisors
Available from: 2012-12-10 Created: 2012-12-10 Last updated: 2012-12-10Bibliographically approved
List of papers
1. Fabrication of monolithic 3D micro-systems
Open this publication in new window or tab >>Fabrication of monolithic 3D micro-systems
2011 (English)In: LAB ON A CHIP, ISSN 1473-0197, Vol. 11, no 2, 288-295 p.Article in journal (Refereed) Published
Abstract [en]

This article describes a method and platform for fast prototyping of monolithic 3D microstructures, capable of producing arbitrary positive, negative and suspended 3D geometries, as well as sealed spaces and aligned 3D geometries using standard photoresists and few fabrication steps. Here a microfabrication method employing a mask-less micro-projection lithography platform, which co-exists on a routine fluorescence microscope, has been refined to produce a variety of 3D microstructures with up to 5 mm spatial resolutions and 10 : 1 aspect ratios, as well as its integration within macroscopic areas of several millimetres with up to 30 mu m spatial resolutions.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2011
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-65715 (URN)10.1039/c0lc00331j (DOI)000285514700014 ()
Available from: 2011-02-18 Created: 2011-02-18 Last updated: 2015-06-01
2. HDR imaging evaluation of a NT-proBNP test with a mobile phone.
Open this publication in new window or tab >>HDR imaging evaluation of a NT-proBNP test with a mobile phone.
2011 (English)In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 26, no 5, 2107-2113 p.Article in journal (Refereed) Published
Abstract [en]

The determination of NT-proBNP levels is key for the monitoring of patients with diagnosed heart failure and it is a routine measurement typically performed at health care centers, which would benefit from decentralized alternatives. Here we investigate the quantitative evaluation of a well-established NT-proBNP test using a standard mobile phone (Nokia 6720) as measuring platform rather than a dedicated instrument. A Java ME software developed for this application controls the illumination and imaging of the proBNP test under defined time intervals, which enables the composition of multi-exposure sets that are processed as high dynamic range (HDR) images for contrast enhancement. The results show that HDR processing significantly increases the sensitivity and resolution of the technique achieving a performance within the diagnostics range. These results demonstrate the feasibility to exploit a ubiquitous device to decentralize the evaluation of a routine test and identify key processing alternatives to bring the performance of such systems within the diagnostics range.

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-63708 (URN)10.1016/j.bios.2010.09.015 (DOI)000286904400051 ()20926279 (PubMedID)
Available from: 2010-12-30 Created: 2010-12-30 Last updated: 2012-12-10Bibliographically approved
3. Embedded Adaptive Optics for Ubiquitous Lab-on-a-Chip Readout on Intact Cell Phones
Open this publication in new window or tab >>Embedded Adaptive Optics for Ubiquitous Lab-on-a-Chip Readout on Intact Cell Phones
2012 (English)In: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 12, no 7, 8586-8600 p.Article in journal (Refereed) Published
Abstract [en]

The evaluation of disposable lab-on-a-chip (LOC) devices on cell phones is an attractive alternative to migrate the analytical strength of LOC solutions to decentralized sensing applications. Imaging the micrometric detection areas of LOCs in contact with intact phone cameras is central to provide such capability. This work demonstrates a disposable and morphing liquid lens concept that can be integrated in LOC devices and refocuses micrometric features in the range necessary for LOC evaluation using diverse cell phone cameras. During natural evaporation, the lens focus varies adapting to different type of cameras. Standard software in the phone commands a time-lapse acquisition for best focal selection that is sufficient to capture and resolve, under ambient illumination, 50 mu m features in regions larger than 500 x 500 mu m(2). In this way, the present concept introduces a generic solution compatible with the use of diverse and unmodified cell phone cameras to evaluate disposable LOC devices.

Place, publisher, year, edition, pages
MDPI, 2012
Keyword
adaptive optics, lab-on-a-chip readout, optical chemical sensing, ubiquitous sensing, cell phones
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-81222 (URN)10.3390/s120708586 (DOI)000306796500010 ()
Note

Funding Agencies|Linkoping Centre for Life Science Technologies (LIST), Sweden||Thammasat University of Thailand for Pakorn Preechaburana||

Available from: 2012-09-10 Created: 2012-09-10 Last updated: 2017-12-07
4. Surface Plasmon Resonance Chemical Sensing on Cell Phones
Open this publication in new window or tab >>Surface Plasmon Resonance Chemical Sensing on Cell Phones
2012 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 51, no 46, 11585-11588 p.Article in journal (Refereed) Published
Abstract [en]

Chemosensing based on angle-resolved surface plasmon resonance is demonstrated on intact cell phones using a disposable optical coupler and software to configure illumination and acquisition. This coupler operates on different cell phones and is applied for classical affinity assays with commercial chips and custom-made tests with embedded calibration. Measured performance (2.14x10−6 refractive index units) is comparable with compact SPR systems.

Place, publisher, year, edition, pages
Wiley Online Library, 2012
Keyword
Analytical methods; cell phone; sensors; surface plasmon resonanced
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-86179 (URN)10.1002/anie.201206804 (DOI)000310875700032 ()
Available from: 2012-12-10 Created: 2012-12-10 Last updated: 2017-12-07Bibliographically approved
5. Disposable total internal reflection fluorescence lab-on-a-chip for medical diagnosis
Open this publication in new window or tab >>Disposable total internal reflection fluorescence lab-on-a-chip for medical diagnosis
Show others...
2012 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Lab-on-a-chip detection of fluorescence transduced chemical stimuli is demonstrated using fluidics and optical coupling disposable elements in a configuration compatible with distributed diagnosis.

Disposable optical elements are designed to separate excitation by total internal reflection using regular glass slides as optical light guide and fluidics support, while high dynamic range image acquisition with consumer cameras complement the platform to support a broad range of responses with a same configuration. Complementary tone mapping procedures are introduced to systematically double the sensitivity for selected range intervals.

Chemical sensitization to free fucose, a diagnostic marker for liver cirrhosis and several cancer forms, illustrates the platform capabilities for diagnosis targets.

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-86181 (URN)
Available from: 2012-12-10 Created: 2012-12-10 Last updated: 2015-06-01Bibliographically approved

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