Publications by authors named "Jussi Hiltunen"

18 Publications

  • Page 1 of 1

Characterization of nucleic acids from extracellular vesicle-enriched human sweat.

BMC Genomics 2021 Jun 9;22(1):425. Epub 2021 Jun 9.

Faculty of Biochemistry and Molecular Medicine, Disease Networks Research Unit, Laboratory of Developmental Biology, Kvantum Institute, Infotech Oulu, University of Oulu, 90014 University of Oulu, Oulu, Finland.

Background: The human sweat is a mixture of secretions from three types of glands: eccrine, apocrine, and sebaceous. Eccrine glands open directly on the skin surface and produce high amounts of water-based fluid in response to heat, emotion, and physical activity, whereas the other glands produce oily fluids and waxy sebum. While most body fluids have been shown to contain nucleic acids, both as ribonucleoprotein complexes and associated with extracellular vesicles (EVs), these have not been investigated in sweat. In this study we aimed to explore and characterize the nucleic acids associated with sweat particles.

Results: We used next generation sequencing (NGS) to characterize DNA and RNA in pooled and individual samples of EV-enriched sweat collected from volunteers performing rigorous exercise. In all sequenced samples, we identified DNA originating from all human chromosomes, but only the mitochondrial chromosome was highly represented with 100% coverage. Most of the DNA mapped to unannotated regions of the human genome with some regions highly represented in all samples. Approximately 5 % of the reads were found to map to other genomes: including bacteria (83%), archaea (3%), and virus (13%), identified bacteria species were consistent with those commonly colonizing the human upper body and arm skin. Small RNA-seq from EV-enriched pooled sweat RNA resulted in 74% of the trimmed reads mapped to the human genome, with 29% corresponding to unannotated regions. Over 70% of the RNA reads mapping to an annotated region were tRNA, while misc. RNA (18,5%), protein coding RNA (5%) and miRNA (1,85%) were much less represented. RNA-seq from individually processed EV-enriched sweat collection generally resulted in fewer percentage of reads mapping to the human genome (7-45%), with 50-60% of those reads mapping to unannotated region of the genome and 30-55% being tRNAs, and lower percentage of reads being rRNA, LincRNA, misc. RNA, and protein coding RNA.

Conclusions: Our data demonstrates that sweat, as all other body fluids, contains a wealth of nucleic acids, including DNA and RNA of human and microbial origin, opening a possibility to investigate sweat as a source for biomarkers for specific health parameters.
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http://dx.doi.org/10.1186/s12864-021-07733-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188706PMC
June 2021

Inkjet-Deposited Single-Wall Carbon Nanotube Micropatterns on Stretchable PDMS-Ag Substrate-Electrode Structures for Piezoresistive Strain Sensing.

ACS Appl Mater Interfaces 2021 Jun 2;13(23):27284-27294. Epub 2021 Jun 2.

Microelectronics Research Unit, University of Oulu, Erkki Koiso-Kanttilan Katu 3, FIN-90570 Oulu, Finland.

Printed piezoresistive strain sensors based on stretchable roll-to-roll screen-printed silver electrodes on polydimethylsiloxane substrates and inkjet-deposited single-wall carbon nanotube micropatterns are demonstrated in this work. With the optimization of surface wetting and inkjet printing parameters, well-defined microscopic line patterns of the nanotubes with a sheet resistance of <100 Ω/□ could be deposited between stretchable Ag electrodes on the plasma-treated substrate. The developed stretchable devices are highly sensitive to tensile strain with a gauge factor of up to 400 and a pressure sensitivity of ∼0.09 Pa, respond to bending down to a radius of 1.5 mm, and are suitable for mounting on the skin to monitor and resolve various movements of the human body such as cardiac cycle, breathing, and finger flexing. This study indicates that inkjet deposition of nanomaterials can complement well other printing technologies to produce flexible and stretchable devices in a versatile manner.
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http://dx.doi.org/10.1021/acsami.1c04397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289179PMC
June 2021

"Plug-n-Play" Polymer Substrates: Surface Patterning with Reactive-Group-Appended Poly-l-lysine for Biomolecule Adhesion.

ACS Appl Polym Mater 2019 Nov 1;1(11):3165-3173. Epub 2019 Oct 1.

Molecular Nanofabrication Group, MESA+ Institute for Nanotechnology, Department of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.

The immobilization of biomolecules onto polymeric surfaces employed in the fabrication of biomedical and biosensing devices is generally a challenging issue, as the absence of functional groups in such materials does not allow the use of common surface chemistries. Here we report the use of modified poly-l-lysine (PLL) as an effective method for the selective modification of polymeric materials with biomolecules. Cyclic olefin polymer (COP), Ormostamp, and polydimethylsiloxane (PDMS) surfaces were patterned with modified PLLs displaying either biotin or maleimide functional groups. Different patterning techniques were found to provide faithful microscale pattern formation, including micromolding in capillaries (MIMIC) and a hydrogel-based stamping device with micropores. The surface modification and pattern stability were tested with fluorescence microscopy, contact angle and X-ray photoelectron spectroscopy (XPS), showing an effective functionalization of substrates stable for over 20 days. By exploiting the strong biotin-streptavidin interaction or the thiol-maleimide coupling, DNA and PNA probes were displayed successfully on the surface of the materials, and these probes maintained the capability to specifically recognize complementary DNA sequences from solution. The printing of three different PNA-thiol probe molecules in a microarray fashion allowed selective DNA detection from a mixture of DNA analytes, demonstrating that the modified PLL methodology can potentially be used for multiplexed detection of DNA sequences.
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http://dx.doi.org/10.1021/acsapm.9b00814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493307PMC
November 2019

Roll-to-Roll Manufacturing of Integrated Immunodetection Sensors.

ACS Sens 2020 07 21;5(7):2010-2017. Epub 2020 Jun 21.

VTT Technical Research Centre of Finland Ltd., Kaitoväylä 1, 90570 Oulu, Finland.

Lack of functional integration and high manufacturing costs have been identified as major challenges in commercialization of point-of-care devices. In this study, roll-to-roll (R2R) fabrication process was developed for large-scale manufacturing of disposable microfluidic devices. The integrated, user-friendly device included a plasma separation membrane for simple blood filtration, immobilized antibodies for specific immunodetection, microfluidics for plasma transport and reagent mixing, and a blister for actuation and waste storage. These functionalities were designed to be compatible with R2R processing, which was demonstrated using pilot-scale printing lines producing 60 devices in an hour. The produced sensors enabled rapid (10 min) and sensitive (2 μg/mL) fluorescence-based immunodetection of C-reactive protein from 20 μL of whole blood.
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http://dx.doi.org/10.1021/acssensors.0c00404DOI Listing
July 2020

Regional and correlative sweat analysis using high-throughput microfluidic sensing patches toward decoding sweat.

Sci Adv 2019 08 16;5(8):eaaw9906. Epub 2019 Aug 16.

Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA.

Recent technological advancements in wearable sensors have made it easier to detect sweat components, but our limited understanding of sweat restricts its application. A critical bottleneck for temporal and regional sweat analysis is achieving uniform, high-throughput fabrication of sweat sensor components, including microfluidic chip and sensing electrodes. To overcome this challenge, we introduce microfluidic sensing patches mass fabricated via roll-to-roll (R2R) processes. The patch allows sweat capture within a spiral microfluidic for real-time measurement of sweat parameters including [Na], [K], [glucose], and sweat rate in exercise and chemically induced sweat. The patch is demonstrated for investigating regional sweat composition, predicting whole-body fluid/electrolyte loss during exercise, uncovering relationships between sweat metrics, and tracking glucose dynamics to explore sweat-to-blood correlations in healthy and diabetic individuals. By enabling a comprehensive sweat analysis, the presented device is a crucial tool for advancing sweat testing beyond the research stage for point-of-care medical and athletic applications.
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http://dx.doi.org/10.1126/sciadv.aaw9906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697435PMC
August 2019

Roll-to-roll fabrication of integrated PDMS-paper microfluidics for nucleic acid amplification.

Lab Chip 2018 05;18(11):1552-1559

VTT-Technical Research Centre of Finland, Kaitoväylä 1, FIN-90590 Oulu, Finland.

Microfluidic-based integrated molecular diagnostic systems, which are automated, sensitive, specific, user-friendly, robust, rapid, easy-to-use, and portable, can revolutionize future medicine. Current research and development largely relies on polydimethylsiloxane (PDMS) to fabricate microfluidic devices. Since the transition from the proof-of-principle phase to clinical studies requires a vast number of integrated microfluidic devices, there is a need for a high-volume manufacturing method of silicone-based microfluidics. Here we present the first roll-to-roll (R2R) thermal imprinting method to fabricate integrated PDMS-paper microfluidics for molecular diagnostics, which allows production of tens of thousands of replicates in an hour. In order to validate the replicated molecular diagnostic platforms, on-chip amplification of viral ribonucleic acid (RNA) with loop-mediated isothermal amplification (LAMP) was demonstrated. These low-cost, rapid and accurate molecular diagnostic platforms will generate a wide range of applications in preventive personalized medicine, global healthcare, agriculture, food, environment, water monitoring, and global biosecurity.
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http://dx.doi.org/10.1039/c8lc00269jDOI Listing
May 2018

Bare laser-synthesized Au-based nanoparticles as nondisturbing surface-enhanced Raman scattering probes for bacteria identification.

J Biophotonics 2018 07 10;11(7):e201700225. Epub 2018 Apr 10.

Aix-Marseille Univ, CNRS, Marseille, France.

The ability of noble metal-based nanoparticles (NPs) (Au, Ag) to drastically enhance Raman scattering from molecules placed near metal surface, termed as surface-enhanced Raman scattering (SERS), is widely used for identification of trace amounts of biological materials in biomedical, food safety and security applications. However, conventional NPs synthesized by colloidal chemistry are typically contaminated by nonbiocompatible by-products (surfactants, anions), which can have negative impacts on many live objects under examination (cells, bacteria) and thus decrease the precision of bioidentification. In this article, we explore novel ultrapure laser-synthesized Au-based nanomaterials, including Au NPs and AuSi hybrid nanostructures, as mobile SERS probes in tasks of bacteria detection. We show that these Au-based nanomaterials can efficiently enhance Raman signals from model R6G molecules, while the enhancement factor depends on the content of Au in NP composition. Profiting from the observed enhancement and purity of laser-synthesized nanomaterials, we demonstrate successful identification of 2 types of bacteria (Listeria innocua and Escherichia coli). The obtained results promise less disturbing studies of biological systems based on good biocompatibility of contamination-free laser-synthesized nanomaterials.
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http://dx.doi.org/10.1002/jbio.201700225DOI Listing
July 2018

Influence of an AlO surface coating on the response of polymeric waveguide sensors.

Opt Express 2017 Oct;25(21):25102-25112

The responses of a polymer ridge waveguide Young interferometer with and without a bilayer of AlO/TiO, fabricated by atomic layer deposition, are studied and compared when applied as an aqueous chemical sensor. The phase shift of the guided mode, as a result of the change in refractive index of the cover medium, is monitored. The results indicate that the over-coating affects the linearity of the sensor response. The effect of concentration on the linearity of the sensor response is investigated by applying different concentrations of water-ethanol solution. Although the performance of the sensor is improved by the additional layers, the study reveals a non-monotonic behavior of the device. We show that it comes mainly from the adsorption of ethanol molecules on the surface of the films. Such an understanding of the platform is crucial for sensing of analytes involving polar molecules.
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http://dx.doi.org/10.1364/OE.25.025102DOI Listing
October 2017

Atmospheric oxidation and carbon contamination of silver and its effect on surface-enhanced Raman spectroscopy (SERS).

Sci Rep 2016 11 16;6:37192. Epub 2016 Nov 16.

Institute of Photonics, University of Eastern Finland, Joensuu, Finland.

Surface-enhanced Raman spectroscopy (SERS) is considered a highly promising technology for different analytical purposes. The applications of SERS are still quite limited due its relatively poor quantitative repeatability and the fact that SERS is very sensitive to oxidation, which is a challenge especially with silver based SERS substrates. Here, the link between these phenomena is investigated by exposing silver SERS substrates to ambient laboratory air. We show that SERS intensity decreases exponentially after the exposure, which consequently leads to an increasing standard deviation (σ) in intensity. Within a five-hour measurement window, the SERS intensity already drops by 60%, while σ triples from 7% to 21%. The SERS results are supplemented by elemental analysis, which shows that oxidation and atmospheric carbon contamination coincide with the rapid SERS intensity decrease. The results emphasize how sensitive SERS is towards atmospheric contamination and how it can also reduce the measurement repeatability - even if the substrates are exposed to air just for a very short period of time.
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http://dx.doi.org/10.1038/srep37192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111099PMC
November 2016

Hybrid layered polymer slot waveguide Young interferometer.

Opt Express 2016 May;24(10):10275-85

We demonstrate a polymer slot waveguide Young interferometer coated with a bilayer of Al2O3/TiO2. The approach enables relaxed dimensions of the polymer waveguide which simplifies the fabrication of the structure with a resolution of 50 nm. The layers were coated by an atomic layer deposition technique. The feasibility of the device was investigated by exploiting the interferometric structure as a bulk refractive index sensor operating at 975 nm wavelength for detection of an ethanol-water solution. A refractive index change of 1 × 10-6 RIU with a sensing length of only 800 µm was detected. The approach confirms the possibility of realizing a low cost device with a small footprint and enhanced sensitivity by employing the TiO2 rails in the sides of the slot waveguide.
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http://dx.doi.org/10.1364/OE.24.010275DOI Listing
May 2016

Disposable photonic integrated circuits for evanescent wave sensors by ultra-high volume roll-to-roll method.

Opt Express 2016 Feb;24(3):2527-41

Flexible photonic integrated circuit technology is an emerging field expanding the usage possibilities of photonics, particularly in sensor applications, by enabling the realization of conformable devices and introduction of new alternative production methods. Here, we demonstrate that disposable polymeric photonic integrated circuit devices can be produced in lengths of hundreds of meters by ultra-high volume roll-to-roll methods on a flexible carrier. Attenuation properties of hundreds of individual devices were measured confirming that waveguides with good and repeatable performance were fabricated. We also demonstrate the applicability of the devices for the evanescent wave sensing of ambient refractive index. The production of integrated photonic devices using ultra-high volume fabrication, in a similar manner as paper is produced, may inherently expand methods of manufacturing low-cost disposable photonic integrated circuits for a wide range of sensor applications.
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http://dx.doi.org/10.1364/OE.24.002527DOI Listing
February 2016

Compensation of drift by using a multichannel integrated Young interferometer.

Appl Opt 2015 May;54(15):4771-80

Polymer-based integrated Young interferometer (YI) sensor chips have proven to be sensitive and have potential to be mass-manufactured. The sensing method is however, disturbed by the mechanical drifts, thus requiring well stabilized and isolated measurement setups that limit its applicability to low-cost readers for rapid diagnostics. In this paper we derive a method for the compensation of mechanical drift by using a multichannel integrated YI chip having two reference channels. The compensation method was demonstrated by quantitative measurements with a three-channel integrated polymeric YI sensor chip using an undisturbed and a mechanically disturbed setup. By applying the compensation method, the intrinsic drift of the undisturbed setup was reduced up to 84%. With the mechanically disturbed setup, the sample-induced phase-change responses were separated up to a 161 times larger disturbed signal.
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http://dx.doi.org/10.1364/AO.54.004771DOI Listing
May 2015

Polymeric slot waveguide interferometer for sensor applications.

Opt Express 2014 Mar;22(6):7229-37

A refractive index sensor based on slot waveguide Young interferometer was developed in this work. The interferometer was fabricated on a polymer platform and operates at a visible wavelength of 633 nm. The phase shift of the interference pattern was measured with various concentrations of glucose-water solutions, utilizing both TE and TM polarization states. The sensor was experimentally observed to detect a refractive index difference of 6.4 × 10(-6) RIU. Furthermore, the slot Young interferometer was found to compensate for temperature variations. The results of this work demonstrate that high performance sensing capability can be obtained with a polymeric slot Young interferometer, which can be fabricated by a simple molding process.
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http://dx.doi.org/10.1364/OE.22.007229DOI Listing
March 2014

Polymeric slot waveguide at visible wavelength.

Opt Lett 2012 Nov;37(21):4449-51

VTT Technical Research Centre of Finland, Oulu, Finland.

Polymeric slot waveguide structure, which pushes the mode field toward the surrounding media, was designed and characterized. The slot waveguide was fabricated by using nanoimprint lithography, and the operation of the slot was demonstrated at 633 nm wavelength with an integrated Young interferometer. The experimental result shows that the nanolithography method provides possibilities to fabricate disposable slot waveguide sensors.
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http://dx.doi.org/10.1364/OL.37.004449DOI Listing
November 2012

Highly sensitive biosensor based on UV-imprinted layered polymeric-inorganic composite waveguides.

Opt Express 2012 Aug;20(18):20309-17

Optoelectronics and Measurement Techniques Laboratory, University of Oulu, PO Box 4500, 90014 Finland.

An evanescent field sensor utilizing layered polymeric-inorganic composite waveguide configuration was developed in this work. The composite waveguide structure consists of a UV-imprint patterned polymer inverted rib waveguide with a Ta2O5 thin film sputter-deposited on top of the low refractive index polymer layers. The results suggest that the polymer based sensor can achieve a detection limit of 3 × 10(-7) RIU for refractive index sensing and corresponding limit of about 100 fg/mm2 for molecular adsorption detection. Besides enhancing the sensitivity significantly, the inorganic coating on the polymer layer was found to block water absorption effectively into the waveguide resulting in a stabilized sensor operation. The ability to use the developed sensor in specific molecular detection was confirmed by investigating antibody - antigen binding reactions. The results of this work demonstrate that high performance sensing capability can be obtained with the developed composite waveguide sensor.
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http://dx.doi.org/10.1364/OE.20.020309DOI Listing
August 2012

Polymeric dual-slab waveguide interferometer for biochemical sensing applications.

Appl Opt 2012 Apr;51(12):1886-93

Optoelectronics and Measurement Techniques Laboratory, University of Oulu, Oulu, Finland.

A polymer based dual-slab waveguide Young's interferometer was demonstrated for biochemical sensing. Evanescent field is utilized for probing the binding events of biomolecules on the waveguide surface. Refractive index sensing in analyte and protein adsorption on the sensing surface were investigated with glucose de-ionized water solution and bovine serum albumin, immunoglobulin G solutions in phosphate buffered saline buffer. A detection limit of 10(-5) RIU and 4 pg/mm(2) was achieved for homogeneous and surface sensing, respectively. Also, the influence of water absorption inside the polymeric device on the measurement stability was evaluated. The results indicate that the waveguide polymer sensor fabricated with the spin coating technique can achieve a satisfactory sensitivity for homogeneous refractive index sensing and, as well, for monitoring molecular binding events on the surface.
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http://dx.doi.org/10.1364/AO.51.001886DOI Listing
April 2012

Nitrogen-doped anatase nanofibers decorated with noble metal nanoparticles for photocatalytic production of hydrogen.

ACS Nano 2011 Jun 24;5(6):5025-30. Epub 2011 May 24.

Microelectronics and Materials Physics Laboratories, Department of Electrical and Information Engineering, University of Oulu, P.O. Box 4500, Oulu FIN-90014, Finland.

We report the synthesis of N-doped TiO(2) nanofibers and high photocatalytic efficiency in generating hydrogen from ethanol-water mixtures under UV-A and UV-B irradiation. Titanate nanofibers synthesized by hydrothermal method are annealed in air and/or ammonia to achieve N-doped anatase fibers. Depending on the synthesis route, either interstitial N atoms or new N-Ti bonds appear in the lattice, resulting in slight lattice expansion as shown by XPS and HR-TEM analysis, respectively. These nanofibers were then used as support for Pd and Pt nanoparticles deposited with wet impregnation followed by calcination and reduction. In the hydrogen generation tests, the N-doped samples were clearly outperforming their undoped counterparts, showing remarkable efficiency not only under UV-B but also with UV-A illumination. When 100 mg of catalyst (N-doped TiO(2) nanofiber decorated with Pt nanoparticles) was applied to 1 L of water-ethanol mixture, the H(2) evolution rates were as high as 700 μmol/h (UV-A) and 2250 μmol/h (UV-B) corresponding to photo energy conversion percentages of ∼3.6 and ∼12.3%, respectively.
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http://dx.doi.org/10.1021/nn201111jDOI Listing
June 2011

Fabrication of optical waveguides by imprinting: usage of positive tone resist as a mould for UV-curable polymer.

Opt Express 2009 Dec;17(25):22813-22

VTT Technical Research Centre of Finland, Kaitovayla 1, Fin-90571 Oulu, Finland.

Optical ridge type waveguides based on UV-curable polymer were fabricated by imprinting method. Positive tone resist patterned on a silicon wafer was used as a mould. The characterization of waveguides was carried out by coupling TE-polarized light from a tapered fiber into a waveguide with 30 mm length and mapping the intensity distribution with another tapered fiber at the output facet of a waveguide. Proper single- or multimode operation was observed depending on the waveguide width being either 2 microm or 6 microm. Experimental observations on the mode profiles were also supported by the simulation results. Average power transmissions of 32% at 1530 nm wavelength and 45% at 1310 nm wavelength were characterized. The results suggest that the simple mould fabrication process might be a useful technique for device prototyping and that the performance of replicated waveguides can meet the requirements for certain applications.
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http://dx.doi.org/10.1364/OE.17.022813DOI Listing
December 2009
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