at the interface of nanotechnology and life sciences

Labelfree detection of insulin

Developing a photonic biosensor for the detection of C-peptide and insulin

In medicine the detection and quantification of specific proteins in blood serum is a well-established method in diagnostics, either in making an initial diagnose or to monitor the effect of a treatment of a patient. Current situation is a general practitioner (GP) or trained assistant is drawing one or two tubes of blood from a patient at the GP’s office, which is subsequently sent to a laboratory. Typically it takes a couple of days before the test results are obtained, which are then communicated to the GP and patient. In many cases this amount of time is simply too long. For patients that are in the hospital already, this time from blood drawing to results is shorter, but still a couple of hours.

In this project we have explored a number of different labelfree detection techniques in order to realize a point-of-care device, that allows detection of proteins within the blood either at the GP's office, or in a next step at home. We focused on diabetes patients, for which fast quantification of their insulin is essential in their therapy. Other proteins that have been studied are CRP and C-peptide.

Starting with surface plasmon resonance imaging, we have optimized the biochemical interface of the sensor in order to allow detection of proteins at low concentrations. Using a hydrogel of several thicknesses coated with the appropriate antibodies, we were able to detect CRP down to a level of 6 ng/mL, which is clinically relevant. For insulin and C-peptide detection, a second antibody was needed in order to detect the proteins at relevant levels. With this second antibody, a limit of detection of 39 and 76 ng/mL were achieved.

In a next step towards creating a smaller point-of-care device, we transferred the biochemistry of the sensor surface to a micro-ring-resonator (MRR), and demonstrated that we were able to detect CRP at various concentration, the lowest one being 125 ng/mL. Experiments with insulin and C-peptide are still ongoing, but we expect to be able to measure clinically relevant values. 

In close collaboration with the NanoPhysics research group we have at the end of the project realized a demonstrator prototype of the device, which includes the chip, the laser source and detector, the electronics and data handling. 

Time period: October 2016 - January 2018
Projectleader: Ron Gill / Martin Bennink
Funding: TechForFuture