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Micromachined Microwave Sensors for Non-Invasive Skin Cancer Diagnostics
KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.ORCID iD: 0000-0002-1934-5856
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Malignant melanoma is one of the cancers with the highest incident rates. It is also the most dangerous skin cancer type and an early diagnosis is crucial for the successful treatment of malignant melanoma patients. If it is diagnosed and treated at an early stage, the survival rate for patients is 99%, however, this is reduced to only 25% if diagnosed at a later stage. The work in this thesis combines microsystem technology, microwave engineering and biomedical engineering to develop a sensing tool for early-stage malignant melanoma diagnostics. Such a tool could not only increase the clinical accuracy of malignant melanoma diagnosis, but also reduce the time needed for examination, and lower the number of unnecessary biopsies. Furthermore, a reliable and easy-to-use tool can enable non-specialist healthcare personnel, including primary care physicians or nurses, to perform a prescreening for malignant melanoma with a high sensitivity. Consequently, a large number of patients could receive a timely examination despite the shortage of dermatologists, which exists in many healthcare systems. The dielectric properties of tumor tissue differ from healthy tissue, which is mainly accounted to a difference in the water content. This difference can be measured by a microwave-based sensing technique called microwave reflectometry. Previously reported microwave-based skin measurements largely relied on standard open-ended waveguide probes that are not suitable for early-stage skin tumor diagnosis. Thus, alternative near-field probe designs based on micromachined dielectric-rod waveguides are presented here. The thesis focuses on a broadband microwave probe that operates in the W-band (75 to 110 GHz), with a sensing depth and resolution tailored to small and shallow skin tumors, allowing a high sensitivity to early-stage malignant melanoma. Prototypes of the probe were fabricated by micromachining and characterized. For the characterization, a novel type of silicon-based heterogeneous sample with tailor-made permittivity was introduced. Furthermore, the performance of the probe was evaluated in vivo. First, through measurements on human volunteers, it was shown that the probe is sensitive to artificially induced changes of the skin hydration. Then, measurements on murine skin melanoma models were performed and small early-stage skin tumors were successfully distinguished from healthy skin. Additionally, a resonant probe for microwave skin sensing was designed and micromachined protoypes were tested on phantom materials. However, the resonant probe was found less suitable than the broadband probe for the measurements on skin. The broadband probe presented in this thesis is the first microwave nearfield probe specifically designed for early-stage malignant melanoma diagnostics and successfully evaluated in vivo.

Abstract [sv]

Malignt melanom är en av våra vanligaste cancertyper och samtidigt den farligaste typen av hudcancer. Tidig diagnosticering är avgörande för en framgångsrik behandling: 99% överlever om den upptäcks tidigt men endast 25% överlever om den upptäcks i sent skede. Denna avhandling kombinerar mikrosystemteknik, mikrovågsteknik, och biomedicinsk forskning för att ta fram ett sensor-verktyg som hjälpmedel för tidig diagnostisering av malignt melanom. I händerna på hudläkare skulle ett sådant verktyg öka noggrannheten på diagnostiseringen, minska undersökningstiden samt antalet onödiga biopsier. Ett pålitligt och lättanvänt verktyg skulle dessutom kunna användas av icke-specialisthälsopersonal t.ex. primärvårdspersonal eller sjuksköterskor. Eftersom många sjukvårdssystem har brist på hudläkare skulle detta möjliggöra att fler patienter får tillgång till tidig undersökning. De dielektriska egenskaperna hos tumörvävnad skiljer sig från hälsosam vävnad vilket huvudsakligen beror på skillnad i vattenhalten. Denna skillnad kan mätas med en mikrovågsbaserad sensorteknik som kallas mikrovågsreflektometri. Tidigare mikrovågsbaserade hudmätningar har i huvudsak förlitat sig på vanliga öppna vågledarprober som inte är lämpliga för att upptäcka hudtumörer i tidigt stadium. I denna avhandling presenteras därför alternativa designer av s.k. närfälts-prober, baserade på mikrotillverkade dielektriska stångvågledare. Avhandlingen fokuserar på en bredbandsprob som arbetar i W-bandet, dvs. 75 till 110 GHz. Dess sensordjup och upplösning är skräddarsydda för små och grunda hudtumörer för att uppnå en hög känslighet för malignt melanom i tidigt stadium. Prototyper av proben framställdes genom mikrotillverkning och karakteriserades med vävnadsliknande material. Det vävnadsliknande materialet specialutvecklades för ändamålet och baseras på en ny typ av kiselbaserade heterogena material med skräddarsydd permittivitet. Sondens prestanda utvärderades dessutom in vivo. Genom mätningar på frivilliga personer bevisades att sonden är känslig för artificiellt inducerad förändring av vattenhalten i huden. Därefter utfördes mätningar på hudcancer i tidigt skede hos möss, där tumörerna framgångsrikt särskildes från frisk hudvävnad. Dessutom konstruerades, tillverkades och testades en s.k. resonans-prob på liknande sätt som tidigare prober. Resonans-proben visade sig dock redan i tester på vävnadsliknande material vara mindre lämplig för hudmätningar. Bredbandsproben som presenteras i denna avhandling är den första närfältsprob som framgångsrikt utvärderats in vivo för diagnosticering av malignt melanom i tidigt stadium.

Place, publisher, year, edition, pages
KTH Royal Institute of Technology, 2019. , p. 84
Series
TRITA-EECS-AVL ; 2019:55
Keywords [en]
microwave probe, microwave sensor, skin cancer diagnostics, malignant melanoma, microwave reflectometry, non-invasive diagnostics, micromachining, dielectric-rod waveguide
National Category
Medical Laboratory and Measurements Technologies Other Electrical Engineering, Electronic Engineering, Information Engineering
Research subject
Electrical Engineering
Identifiers
URN: urn:nbn:se:kth:diva-252543ISBN: 978-91-7873-236-4 (print)OAI: oai:DiVA.org:kth-252543DiVA, id: diva2:1319427
Public defence
2019-08-23, F3, Lindstedtsvägen 26, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20190603

Available from: 2019-06-03 Created: 2019-05-31 Last updated: 2019-06-03Bibliographically approved
List of papers
1. Millimeter-Wave Near-Field Probe Designed for High-Resolution Skin Cancer Diagnosis
Open this publication in new window or tab >>Millimeter-Wave Near-Field Probe Designed for High-Resolution Skin Cancer Diagnosis
2015 (English)In: IEEE transactions on microwave theory and techniques, ISSN 0018-9480, E-ISSN 1557-9670, Vol. 63, no 6, p. 2050-2059Article in journal (Refereed) Published
Abstract [en]

This paper presents a detailed technical characterization of a micromachined millimeter-wave near-field probe developed for skin cancer diagnosis. The broadband probe is optimized for frequencies from 90 to 104 GHz and consists of a dielectric- rod waveguide, which is metallized and tapered towards the tip to achieve high resolution by concentrating the electric field in a small sample area. Several probes with different tip sizes were fabricated from high-resistivity silicon by micromachining and were successfully characterized using silicon test samples with geometry- defined tailor-made permittivity. The probes show a high responsivity for samples with permittivities in the range of healthy and cancerous skin tissue at 100 GHz (from 3.2 - j2.3 to 7.2 - j8.0, loss tangent of approximately 1.26). The sensing depth was determined by simulations and measurements from 0.3 to 0.4 mm, which is adapted for detecting early-stage skin tumors before they metastasize. The lateral resolution was determined to 0.2 mm for a tip size of 0.6 x 0.3 mm, which allows for resolving small skin tumors and inhomogeneities within a tumor.

National Category
Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-170690 (URN)10.1109/TMTT.2015.2428243 (DOI)000355930300027 ()2-s2.0-84958103391 (Scopus ID)
Note

QC 20150707

Available from: 2015-07-07 Created: 2015-07-03 Last updated: 2019-05-31Bibliographically approved
2. Millimeter-Wave Tissue Diagnostics: The most promising fields for medical applications
Open this publication in new window or tab >>Millimeter-Wave Tissue Diagnostics: The most promising fields for medical applications
2015 (English)In: IEEE Microwave Magazine, ISSN 1527-3342, E-ISSN 1557-9581, Vol. 16, no 4, p. 97-113, article id 7072578Article in journal (Refereed) Published
Abstract [en]

At the end of the 19th century, researchers observed that biological substances have frequency-dependent electrical properties and that tissue behaves like a capacitor [1]. Consequently, in the first half of the 20th century, the permittivity of many types of cell suspensions and tissues was characterized up to frequencies of approximately 100 MHz. From the measurements, conclusions were drawn, in particular, about the electrical properties of the cell membranes, which are the main contributors to the tissue impedance at frequencies below 10 MHz [2]. In 1926, a study found a significant different permittivity for breast cancer tissue compared with healthy tissue at 20 kHz [3]. After World War II, new instrumentation enabled measurements up to 10 GHz, and a vast amount of data on the dielectric properties of different tissue types in the microwave range was published [4]-[6].

Keywords
Basal-Cell Carcinoma, Microwave Dielectric-Properties, Breast-Cancer Detection, Near-Field Microwave, Ended Coaxial Probe, Free-Water Content, Human-Skin, Biological Tissues, In-Vivo, Micromachined Probe
National Category
Telecommunications Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-166316 (URN)10.1109/MMM.2015.2394020 (DOI)000352622500011 ()2-s2.0-84926649905 (Scopus ID)
Note

QC 20150512

Available from: 2015-05-12 Created: 2015-05-07 Last updated: 2019-05-31Bibliographically approved
3. Long-Term Monitoring of Skin Recovery by Micromachined Microwave Near-Field Probe
Open this publication in new window or tab >>Long-Term Monitoring of Skin Recovery by Micromachined Microwave Near-Field Probe
2017 (English)In: IEEE Microwave and Wireless Components Letters, ISSN 1531-1309, E-ISSN 1558-1764, Vol. 27, no 6, p. 605-607Article in journal (Refereed) Published
Abstract [en]

The water content in the epidermis correlates with different pathologic states of the skin; thus its assessment can aid the diagnosis and monitoring of conditions such as inflammation, edema, burns, and skin cancer. A micromachined microwave near-field probe, operating from 90 to 106 GHz, which, in contrast to earlier used microwave probes, has a minimized sensing area of 0.6 mm x 0.5 mm and an optimized sensing depth of 400 mu m in tissue, has been developed and technically characterized by the authors earlier. This letter reports on the long-term monitoring of sodium lauryl sulfate (SLS)-induced skin irritations with the micromachined microwave probe. Aqueous solutions with 1%, 2%, 5%, and 10% SLS were applied to the forearm of a volunteer for 24 h and microwave reflection measurements were taken before and during 11 days after the SLS application. For all SLS-treated spots the microwave absorption reached the highest levels of 4 to 7 days after SLS application and afterward converged toward baseline levels again. The observed biphasic progression of the microwave reflection signal agrees well with trends from the literature for capacitance measurements and for epidermal thickness and signal attenuation in optical coherence tomography after SLS exposure. The measurements indicate that the microwave probe is very suitable to determine changes in the water content in the epidermis and can aid in the diagnosis of pathologic conditions including skin cancer.

Place, publisher, year, edition, pages
Institute of Electrical and Electronics Engineers (IEEE), 2017
Keywords
Medical application, micromachining, monitoring, near-field probe, skin cancer, sodium lauryl sulfate (SLS)
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:kth:diva-210427 (URN)10.1109/LMWC.2017.2701336 (DOI)000403292100025 ()2-s2.0-85020079085 (Scopus ID)
Funder
VINNOVA
Note

QC 20170630

Available from: 2017-06-30 Created: 2017-06-30 Last updated: 2019-05-31Bibliographically approved
4. In Vivo Evaluation of Microwave Probe for Early-Stage Malignant Melanoma Diagnostics: Measurements on Murine Tumor Model
Open this publication in new window or tab >>In Vivo Evaluation of Microwave Probe for Early-Stage Malignant Melanoma Diagnostics: Measurements on Murine Tumor Model
(English)Manuscript (preprint) (Other academic)
National Category
Medical Engineering Other Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-252546 (URN)
Note

QC 20190603

Available from: 2019-05-31 Created: 2019-05-31 Last updated: 2019-06-03Bibliographically approved
5. Millimeter wave silicon micromachined waveguide probe as an aid for skin diagnosis - results of measurements on phantom material with varied water content
Open this publication in new window or tab >>Millimeter wave silicon micromachined waveguide probe as an aid for skin diagnosis - results of measurements on phantom material with varied water content
Show others...
2014 (English)In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 20, no 1, p. 116-123Article in journal (Refereed) Published
Abstract [en]

Background: More than 2 million cases of skin cancer are diagnosed annually in the United States, which makes it the most common form of cancer in that country. Early detection of cancer usually results in less extensive treatment and better outcome for the patient. Millimeter wave silicon micromachined waveguide probe is foreseen as an aid for skin diagnosis, which is currently based on visual inspection followed by biopsy, in cases where the macroscopical picture raises suspicion of malignancy. Aims: Demonstration of the discrimination potential of tissues of different water content using a novel micromachined silicon waveguide probe. Secondarily, the silicon probe miniaturization till an inspection area of 600 × 200 μm2, representing a drastic reduction by 96.3% of the probing area, in comparison with a conventional WR-10 waveguide. The high planar resolution is required for histology and early-state skin-cancer detection. Material and methods: To evaluate the probe three phantoms with different water contents, i.e. 50%, 75% and 95%, mimicking dielectric properties of human skin were characterized in the frequency range of 95-105 GHz. The complex permittivity values of the skin are obtained from the variation in frequency and amplitude of the reflection coefficient (S11), measured with a Vector Network Analyzer (VNA), by comparison with finite elements simulations of the measurement set-up, using the commercially available software, HFSS. The expected frequency variation is calculated with HFSS and is based on extrapolated complex permittivities, using one relaxation Debye model from permittivity measurements obtained using the Agilent probe. Results: Millimeter wave reflection measurements were performed using the probe in the frequency range of 95-105 GHz with three phantoms materials and air. Intermediate measurement results are in good agreement with HFSS simulations, based on the extrapolated complex permittivity. The resonance frequency lowers, from the idle situation when it is probing air, respectively by 0.7, 1.2 and 4.26 GHz when a phantom material of 50%, 75% and 95% water content is measured. Discussion: The results of the measurements in our laboratory set-up with three different phantoms indicate that the probe may be able to discriminate between normal and pathological skin tissue, improving the spatial resolution in histology and on skin measurements, due to the highly reduced area of probing. Conclusion: The probe has the potential to discriminate between normal and pathological skin tissue. Further, improved information, compared to the optical histological inspection can be obtained, i.e. the complex permittivity characterization is obtained with a high resolution, due to the highly reduced measurement area of the probe tip.

Keywords
skin cancer, phantom, dielectric constant, mm-wave
National Category
Engineering and Technology Medical and Health Sciences
Identifiers
urn:nbn:se:kth:diva-140655 (URN)10.1111/srt.12093 (DOI)000329500800018 ()2-s2.0-84892367978 (Scopus ID)
Funder
Vinnova
Note

QC 20140131

Available from: 2014-01-31 Created: 2014-01-30 Last updated: 2019-05-31Bibliographically approved
6. Optimization of Micromachined Millimeter-Wave Planar Silicon Lens Antennas with Concentricand Shifted Matching Regions
Open this publication in new window or tab >>Optimization of Micromachined Millimeter-Wave Planar Silicon Lens Antennas with Concentricand Shifted Matching Regions
Show others...
2017 (English)In: Progress In Electromagnetics Research C, ISSN 1937-8718, E-ISSN 1937-8718, Vol. 79, p. 17-29Article in journal (Refereed) Published
Abstract [en]

This paper presents a study of planar silicon lens antennas with up to three stepped-impedance matching regions. The effective permittivity of the matching regions is tailor-made byetching periodic holes in the silicon substrate. The optimal thickness and permittivity of the matchingregions were determined by numerical optimization to obtain the maximum wideband aperture efficiencyand smallest side-lobes. We introduce a new geometry for the matching regions, referred to as shiftedmatching regions. The simulation results indicate that using three shifted matching regions results intwice as large aperture efficiency as compared to using three conventional concentric matching regions.By increasing the number of matching regions from one to three, the band-averaged gain is increasedby 0.3 dB when using concentric matching regions, and by 3.7 dB when using shifted matching regions,which illustrates the advantage of the proposed shifted matching region design.

National Category
Electrical Engineering, Electronic Engineering, Information Engineering
Research subject
Electrical Engineering
Identifiers
urn:nbn:se:kth:diva-197335 (URN)
Note

QC 20161115

Available from: 2016-12-03 Created: 2016-12-03 Last updated: 2019-06-03Bibliographically approved

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