Lab-on-a-chip

Lab-on-a-chip

Biophotonic sensor platform for diagnostics

Project overview

Project lead: Astrid Aksnes
Institution: NTNU
Partners: Department of Electronic Systems NTNU (host), Department of Cancer Research and Molecular Medicine NTNU, Department of Physics NTNU, Microsystems and Nanotechnology SINTEF Digital, og Centre of Molecular Inflammation Research (CEMIR) at NTNU/S
Funding: NOK 22.8 mill.
Duration: 2016–11/1/2021

Publications

  • Yadav, Mukesh & Aksnes, Astrid (2022). Multiplexed Mach-Zehnder interferometer assisted ring resonator sensor. Optics Express. ISSN 1094-4087. 30, p. 1388–1396. doi: 10.1364/OE.448023. Full text in Research Archive
  • Sønstevold, Linda; Yadav, Mukesh; Arnfinnsdottir, Nina Bjørk; Herbjørnrød, Aina Kristin; Jensen, Geir Uri & Aksnes, Astrid [Show all 7 contributors for this article] (2022). Biocompatible bonding of a rigid off-stoichiometry thiol-ene-epoxy polymer microfluidic cartridge to a biofunctionalized silicon biosensor. Journal of Micromechanics and Microengineering (JMM). ISSN 0960-1317. 32(7). doi: 10.1088/1361-6439/ac6ebf. Full text in Research Archive
  • Yadav, Mukesh; Noh, Jong Wook; Hjelme, Dag Roar & Aksnes, Astrid (2021). Spectral shaping of ring resonator transmission response. Optics Express. ISSN 1094-4087. 29(3), p. 3764–3771. doi: 10.1364/OE.415683. Full text in Research Archive
  • Høvik, Jens; Yadav, Mukesh; Noh, Jong Wook & Aksnes, Astrid (2020). Waveguide asymmetric long-period grating couplers as refractive index sensors. Optics Express. ISSN 1094-4087. 28(16), p. 23936–23949. doi: 10.1364/OE.397561. Full text in Research Archive
  • Arnfinnsdottir, Nina Bjørk; Chapman, Cole A; Bailey, Ryan C; Aksnes, Astrid & Stokke, Bjørn Torger (2020). Impact of Silanization Parameters and Antibody Immobilization Strategy on Binding Capacity of Photonic Ring Resonators. Sensors. ISSN 1424-8220. 20(11). doi: 10.3390/s20113163. Full text in Research Archive
  • Saadat, Amir; Huyke, Diego A.; Oyarzun, Diego I.; Escobar, Paulina V.; Øvreeide, Ingrid Haga & Shaqfeh, Eric S.G. [Show all 7 contributors for this article] (2020). A system for the high-throughput measurement of the shear modulus distribution of human red blood cells. Lab on a Chip. ISSN 1473-0197. 20(16), p. 2927–2936. doi: 10.1039/D0LC00283F.
  • Yadav, Mukesh; Høvik, Jens; Hjelme, Dag Roar & Aksnes, Astrid (2018). Sensitivity enhanced biophotonic sensor utilizing sub-wavelength gratings. Proceedings of SPIE, the International Society for Optical Engineering. ISSN 0277-786X. 10729. doi: 10.1117/12.2321165.

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  • Yadav, Mukesh; Noh, Jong Wook; Hjelme, Dag Roar & Aksnes, Astrid (2020). Hybrid ring resonator sensor with high quality factor and wide dynamic range.
  • Arnfinnsdottir, Nina Bjørk (2019). Biofunctionalization of a photonic ring resonator sensor .
  • Yadav, Mukesh; Høvik, Jens; Noh, Jong Wook; Hjelme, Dag Roar & Aksnes, Astrid (2019). Silicon photonic waveguide sensor.
  • Yadav, Mukesh; Noh, Jong Wook; Høvik, Jens & Aksnes, Astrid (2019). Fabrication and characterization of silicon photonic sensor.
  • Arnfinnsdottir, Nina Bjørk (2019). Seminar.
  • Aksnes, Astrid; Høvik, Jens; Yadav, Mukesh; Noh, Jong Wook; Hjelme, Dag Roar & Milenko, Karolina Barbara [Show all 9 contributors for this article] (2019). Photonics activities at IES: LOC biosensor project and Artificial intraperitoneal pancreas project.
  • Huyke, Diego A.; Oyarzun, Diego I.; Saadat, Amir; Øvreeide, Ingrid Haga; Escobar, Paulina V. & Shaqfeh, Eric S.G. [Show all 7 contributors for this article] (2019). High-throughput measurements of red blood cell deformation in microfluidic channels .
  • Arnfinnsdottir, Nina Bjørk; Høvik, Jens; Aksnes, Astrid & Stokke, Bjørn Torger (2018). Correlation of surface characteristics with photonic biosensor performance.
  • Høvik, Jens; Arnfinnsdottir, Nina Bjørk & Aksnes, Astrid (2018). A comparative study of photonic transducers for lab-on-a-chip biosensors.
  • Høvik, Jens & Aksnes, Astrid (2018). Loss reduction of electron-beam lithography fabricated strip wire waveguide bends.
  • Yadav, Mukesh & Aksnes, Astrid (2018). Phase-modulated Mach-Zehnder interferometer sensor.
  • Høvik, Jens & Aksnes, Astrid (2018). Experimental validation of a 2D approximation method for investigating photonic components: case study refractive index sensor.
  • Aksnes, Astrid (2018). Digital Life Board Meeting: Lab-on-a-chip biophotonic sensor project: status and plans .
  • Yadav, Mukesh; Høvik, Jens; Hjelme, Dag Roar & Aksnes, Astrid (2018). Sensitivity enhanced biophotonic sensor utilizing sub-wavelength gratings.
  • Yadav, Mukesh; Høvik, Jens & Aksnes, Astrid (2018). Highly sensitive lab-on-a-chip biosensor utilizing phase-modulated Mach-Zehnder interferometer.
  • Høvik, Jens; Arnfinnsdottir, Nina Bjørk; Yadav, Mukesh & Aksnes, Astrid (2018). Lab-on-a-chip photonic biosensor for detection of antigens.
  • Øvreeide, Ingrid Haga; Arnfinnsdottir, Nina Bjørk; Mielnik, Michal Marek & Stokke, Bjørn Torger (2018). Characterization of passive mixing structures in microfluidic channels.
  • Øvreeide, Ingrid Haga; Arnfinnsdottir, Nina Bjørk; Mielnik, Michal Marek & Stokke, Bjørn Torger (2018). Characterization of model biomarker mass transfer in microfluidic Y-channels.
  • Yadav, Mukesh; Noh, Jong Wook & Aksnes, Astrid (2018). Conformal high aspect ratio fill using RF sputtering.
  • Høvik, Jens & Aksnes, Astrid (2017). A study on the optical properties of amorphous silicon.
  • Yadav, Mukesh; Høvik, Jens & Aksnes, Astrid (2017). Optical Waveguides and Gratings.
  • Aksnes, Astrid (2017). Lab-on-a-chip Biophotonic Sensor Platform for Rapid Disease Diagnosis.
  • Aksnes, Astrid (2017). Utvikler laboratorium på én brikke. [Business/trade/industry journal]. Elektronikk 03/2017.
  • Arnfinnsdottir, Nina Bjørk; Øvreeide, Ingrid Haga; Aksnes, Astrid; Mielnik, Michal Marek; Stokke, Bjørn Torger & Halaas, Øyvind (2017). Lab-On-a-Chip Biophotonic Sensor Platform: Biofunctionalization and Microfluidic Design.
  • Hjelme, Dag Roar (2017). A Lower Bound on the Resolution Limit of Resonant Refractive Index Sensors.
  • Høvik, Jens & Aksnes, Astrid (2017). Lab-on-a-Chip Biophotonic Sensor Platform: Frequency separated multiplexed optical biosensing.
  • Høvik, Jens & Aksnes, Astrid (2017). Ring resonators as refractive index sensors.
  • Høvik, Jens & Aksnes, Astrid (2016). Fabrication of photonic components for integrated lab-on-a-chip biosensor.
  • Høvik, Jens & Aksnes, Astrid (2016). A study of approximations for accurate two-dimensional simulations of photonic SOI components.
  • Høvik, Jens & Aksnes, Astrid (2016). Photonic Crystal Resonators as Transduction Elements for Biosensing.

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Research group

Tests for many diseases simultaneously

Doctors can make accurate diagnoses much faster if they have access to a microlaboratory in their office that can analyze samples from a patient in minutes.
 Scientists from NTNU in Trondheim and SINTEF in Oslo are developing a lab-on-a-chip, which is only a few square centimeters. This tiny device will be able to reveal a number of different diseases from the same patient sample, whether it is blood, saliva or urine.

This microlaboratory, also called lab-on-a-chip (LOC), draws the patient sample through thin channels, only a few tens of micrometers thick. The microfluidic channels deliver the samples to the sensors, which are surface functionalized for attachment of different biomarkers. These biomarkers are specific for the diseases one wishes to check. The design of the LOC sensor platform enables a single chip to analyze many substances within tens of minutes. Today, samples are usually sent to a laboratory and it takes many hours or even several days until the doctor will get an answer.

Initially, the researchers will create a prototype that measures three biomarkers used in the analysis of blood samples. These biomarkers are inflammation markers that indicate different conditions, inflammation from bacteria or viruses, potentially cancer and kidney failure. The goal is to create a lab-on-a-chip that is so cheap that it can be discarded after use, and be used both in doctors' offices and in the Third World.

This groundbreaking project combines expertise from medicine, bioengineering, micro-/ nanofluidics (deals with the behavior and precise control of fluids) and nanophotonics (a branch of optical engineering where light interacts with nanoscale structures).

The project is managed by the Department of Electronic Systems at NTNU. Partners are the Department of Physics at NTNU, Department of Cancer Research and Molecular Medicine at NTNU, Department of Microsystems and Nanoelectronics (MiNaLab) at SINTEF Digital, and Centre of Molecular Inflammation Research (CEMIR) at NTNU / St. Olav's Hospital.

More about the project

Biomarkers and nanosensors on lab-on-a-chip

In the Lab-on-a-chip (LOC) Biophotonic Sensor Platform for Diagnostics project, scientists will develop a medical analysis lab-on-a-chip, only a few square centimeters large. To achieve this goal the project combines knowledge of medicine, bioengineering, nanophotonics, micro-/nanofluidics and electronics.

When a person is sick, blood or other bodily fluids may contain proteins specific to an illness or group of diseases. This is called a disease biomarker, and is useful for diagnosis of disease from infections and cancer to kidney failure. By measuring the amount of such biomarkers physicians can obtain quantitative information to help make the diagnosis and choose the right course of treatment.

In this project, the researchers miniaturize the components comprising the analysis equipment. A prototype chip will be developed containing four multiplexed sensors with different surface functionalization. Each sensor will be sensitive to one specific biomarker. Microfluidic channels will transport the fluids containing target biomarkers to these sensors.

The prototype will contain one reference sensor and three sensors with different biomarkers: C-reactive protein (CRP) showing bacterial inflammation in the body, lipocalin 2 (LCN2) as a potential marker of kidney failure, and tumor necrosis factor (TNF) that is elevated by inflammation in the body by arthritis, but may also indicate early stage cancer.

The three selected biomarkers were chosen partly because of their difference in blood concentration, from micrograms per milliliter down to a few picograms (trillion gram), which requires very sensitive measuring equipment. Today, such biomarkers are mainly analyzed in well-equipped laboratories. Here they require relatively large sample volume and it may take hours before the result is ready.

In the project, the researchers will create a LOC demonstrator the size of a postage stamp, where the smallest components are a few hundred nanometers. The advantage of making the LOC so little is that it only needs small sample volumes, approximately 15 microliters. Further, the samples are analyzed quickly with a goal of maximum 20 minutes. In the long term, the goal is to develop a chip with a large number of multiplexed sensors that can measure the biomarkers simultaneously.

Results from the analysis of samples using the LOC will be compared with the gold standard for blood samples in hospitals today - ELISA (Enzyme-linked Immunosorbent Assay).

The project will develop all the three main components integrated on a chip:

  • Photonic sensors that are micro- to nanometer in size.
  • Surface functionalized sensors with molecules that capture the target biomarkers.
  • Microfluidic channels that guide the transport of fluids (patient samples) containing biomarkers to the sensors.

NTNU Nanolab is an important infrastructure needed to fabricate the minute chip, as well as the MiNaLab at SINTEF in Oslo.

Interdisciplinary

To succeed with such a dramatic reduction in size of a «laboratory» the project gathers scientists from different fields combining competence within nanophotonics, bioengineering, nanofluidics, immunology, and clinical applications. Each field has its own jargon (language) where even the same word may have a different meaning between disciplines. Through several two-day seminars, project participants from the various disciplines and institutions meet, discuss and make specifications for the physical prototype of lab-on-a-chip. This has generated better understanding for each other's disciplines.

Two PhD students and two postdoctoral fellows are funded by the Digital Life project while another PhD student is funded by a NTNU strategic enabling technology project. Some of them are physically in the same environment as PhD students and post-docs in another Digital Life project, the Double Intraperitoneal Artificial Pancreas project. Several of the students are affiliated to the PhD Network for Nanotechnology and Microsystems Research School and the Digital Life Research School.

The project collaborates with the Center for Digital Life Norway on responsible research and innovation (RRI). A number of dissemination activities aim at creating awareness, triggering interaction, and collecting valuable feedback from target stakeholder groups (industry, patient associations, medical practitioners, health personnel, health decision makers) thus maximizing the impact and exploitation opportunities of the LOC Biosensor. The vision for the lab-on-a-chip project is to contribute to an analysis equipment, which is so simple and cheap to use that it is found at any doctor’s office.

Innovation

The lab-on-a-chip project extends the existing technology to the limit. Five years is therefore a too short timeframe for development of these pioneering lab-on-a-chips to a commercial product. However, the project has an Advisory Board with representatives from industry, several with experience in start-ups. This panel will provide advice on how the results can be developed commercially beyond the end of this project.

Watch presentation of the project

At the Digital Life 2020 conference project leader Astrid Aksnes talked about the project.
Watch recording of her talk