A generic lab-on-a-chip (LOC) biophotonic platform capable of performing highly sensitive and selective multiplexed quantitative diagnostic tests has been developed. Early and reliable detection of diseases is highly desirable because it dramatically increases the chance for successful treatment. Project manager is prof. Astrid Aksnes at the Department of Electronic Systems, Norwegian University of Science and Technology (NTNU). Highly qualified researchers from NTNU and SINTEF work closely together on the project, which is funded by the Norwegian Research Council.
Work is underway to develop a tiny lab-on-a-chip that can analyze the contents of patient samples quickly and accurately. The chip containing the sensors is approximately 1 square millimeter. Minute volumes of sample fluid are transported to the sensors using microfluidic channels. By modifying the surface functionalization of the multiplexed photonic sensing elements, different biomarkers can be detected in parallel to achieve ng/ml to pg/ml limit of detection (LOD). This enables numerous biomedical applications such as diagnosis of infectious diseases and potentially cancer. Early identification and quantification of the biomarkers for the various diseases is essential for successful treatment.
Multiple channels have been produced on the same chip and different concentrations have been measured in the different channels. Two new sensor designs have been developed that further improve the LOD, so we measure concentrations on the order of ng-µg /ml. One of these designs allows multiplexing of several sensors in one channel by generating a unique signature for each sensor. Different physiological concentrations of the biomarker C-reactive protein RP) have been measured and the specified detection limit reached (<5 µg / ml). In addition, Cod-Vtg has been measured with a detection limit of approximately 100 ng/ml.
Passive mixers have been integrated into the microfluidic channels to transport the biomarkers more efficiently onto the sensor surface. The mixing efficiency of different passive mixer designs has been simulated and measured. Future work includes testing these passive mixers integrated with the biosensors. Processes Ostemer-based microfluidics have been developed allowing integration of nanofluidic patterns in the channels while enabling biocompatible bonding to the sensor chip.
Resultatene er interessante for sensorindustrien når det gjelder bedre deteksjonsgrense, større måleområde, multipleksing av sensorer, prosesser for fremstilling av mikro/nanofluidikken, og effektiv blanding og massetransport.
- 2 sensordesign som forbedrer deteksjonsgrensen ble utviklet. Det ene, Mach-Zehnder assistert ring resonator konfigurasjon (MARC) kan realisere transmisjonsspekter med unike spektralsignaturer og signifikant større effektivt fritt spektralområde sammenlignet med konvensjonelle RR. Det ble søkt patent på MARC prinsippet i mars 2020.
- Prosesser for fremstilling av OSTE (off-stoichiometry thiol-enes) mikro/nanofluidikk har blitt utviklet. OSTE er et lovende materiale for mikro/nanofluidikken for oppskalering.
- Effektiv blanding og massetransport ble oppnådd ved hjelp av buede passive blandestrukturer. Disse er mer robuste for å oppnå effektiv prøvehomogenisering enn den kjente fiskebeinstrukturen mht variasjon i parameterne til blandestrukturene.
The ultimate goal of this project is to develop a generic lab-on-a-chip (LOC) label-free biophotonic sensor platform capable of performing highly sensitive and selective multiplexed quantitative diagnostic tests. By modifying the surface functionalization of the multiplexed photonic sensing elements, different biomarkers can be detected in parallel with ng/ml - pg/ml limit of detection (LOD). This enables numerous biomedical applications such as diagnosis of cancer and infectious diseases (e.g HIV and tuberculosis).
This proposal combines research efforts in bioengineering, nanofluidics, and nano-photonics to achieve progress beyond the state-of-the-art pushing technology from the lab bench towards a miniaturized LOC sensor platform with potential for mass production. The innovative design of the separately biofunctionalized photonic crystal sensing elements integrated with nanofluidic circuits allows arrays of sensors on a millimeter squared-sized chip to be analyzed in <20 min.
In our choice of biomarkers for the demonstrator, we take advantage of our expertise in immunology and inflammation at St Olavs University Hospital and NTNU. Our demonstrator will include three target biomarkers: Lipocalin 2 (LCN2), c-reactive protein (CRP), and tumour necrosis factor (TNF). CRP is a well-characterized and established biomarker in clinical use and will be used to qualify the performance of the biophotonic sensor platform. TNF is an established marker relevant for monitoring certain inflammatory diseases and also for inflammation research purposes. LCN2 is an antibacterial protein with potential as inflammatory biomarker. LCN2 can be measured in blood serum or plasma, in feces and in urine, and it is currently under development for potential use as a diagnostic marker for kidney failure.