Lab-on-a-chip

Lab-on-a-chip. Biophotonic sensor platform for diagnostics.

Schematic illustration of the lab-on-a-chip biophotonic sensor with microfluidic channels

Tests for many diseases simultaneously

The 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.

Project information

  • Category:
    Health
  • Duration:
    2016 - 2020
  • Funding:
    22,8 mill. kr
  • Institution:
    NTNU

Project lead

Astrid Aksnes

E-mail: astrid.aksnes@ntnu.no

Profil

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

  • More about the project
  • Publications
  • Participants

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.

Participants

  • Reinold Ellingsen

    Reinold Ellingsen

    Senior Advisor, Dept. of Electronic Systems

    Member of APT's steering group. Sharing responsibility with APT members on sensor technology and development, including IP. Co-supervisor of PhD and post.doc within optical sensor technology.

    Profile

  • Astrid Aksnes

    Astrid Aksnes

    Professor, Dept. of Electronic Systems

    Supervisor for PhD students and postdocs doing research on optical spectroscopy (Raman and mid-IR) of peritoneal fluid. Project leader for the DLN project 'Lab-on-a-chip biophotonic sensor platform for diagnostics'.

    Profile

  • Dag Roar Hjelme

    Dag Roar Hjelme

    Professor, Dept. of Electronic Systems

    Supervisor for PhD students doing research on optical spectroscopy of peritoneal fluid.

    Profile

  • Nina Bjørk Arnfinnsdottir

    Nina Bjørk Arnfinnsdottir

    Post doc, Department of Cancer Research and Molecular Medicine

    I work with surface functionalization of the photonic biosensor for the selective capture of biomarkers.

  • Trude Helen Flo

    Trude Helen Flo

    Professor in Cell Biology and Co-Director of CEMIR (Centre of Molecular Inflammation Research), CEMIR and Department of Cancer Research and Molecular Medicine

    Work Package leader (WP4) with responsibility for testing the sensor and comparing with commercially available and comparable methods for measuring the biomarkers in question (TNF, Lcn2, CRP).

  • Kay Gastinger

    Kay Gastinger

    Direktør, NTNU NanoLab

    Project participant with the work packages in optical sensor technology, and dissemination and exploitation.

  • Jens Høvik

    Jens Høvik

    PhD Candidate, Department of Electronic Systems

    PhD student for Lab-on-a-chip biophotonic sensor platform for diagnostics project. Responsible for photonic sensor design and fabrication.

  • Michal Mielnik

    Michal Mielnik

    Research Manager, ICT, Microsystems and Nanotechnology (MiNaLab)

    Work package leader for WP3, Nanofluidic design.

  • Bjørn Torger Stokke

    Bjørn Torger Stokke

    Professor, Department of Physics

    Project participant in LOC project with emphasis on surface modification and bioconjugation and nanofluidic design.