Label-free multiplex sensing from buffer and immunoglobulin G sensing from whole blood with photonic crystal slabs using angle-tuning of an optical interference filter

Abstract

Direct detection of biomarkers from unpurified whole blood has been a challenge for label-free detection platforms, such as photonic crystal slabs (PCS). A wide range of measurement concepts for PCS exist, but exhibit technical limitations, which render them unsuitable for label-free biosensing with unfiltered whole blood. In this work, we single out the requirements for a label-free point-of-care setup based on PCS and present a wavelength selecting concept by angle tuning of an optical interference filter, which fulfills these requirements. We investigate the limit of detection (LOD) for bulk refractive index changes and obtain a value of 3.4 E-4 refractive index units (RIU). We demonstrate label-free multiplex detection for different types of immobilization entities, including aptamers, antigens, and simple proteins. For this multiplex setup we detect thrombin at a concentration of 6.3 µg/ml, antibodies of glutathione S-transferase (GST) diluted by a factor of 250, and streptavidin at a concentration of 33 µg/ml. In a first proof of principle experiment, we demonstrate the ability to detect immunoglobulins G (IgG) from unfiltered whole blood. These experiments are conducted directly in the hospital without temperature control of the photonic crystal transducer surface or the blood sample. We set the detected concentration levels into a medical frame of reference and point out possible applications.

Intensity-Based Camera Setup for Refractometric and Biomolecular Sensing with a Photonic Crystal Microfluidic Chip

“…Using whole blood as the sample is a challenge, since it is a highly complex fluid. While label-free sensing from whole blood has been shown [68], no works based on PCS (apart our work in [47]) regarding this matter have been reported. Jahns et al [69] used a filter to rid the whole blood of its solid constituents.…”

“…The rather moderate intensity changes of approximately 3.5 a.u. shown here stem from the fact that the majority of the signal change occurs within a few seconds after exposure to whole blood [47]. This is shown in the Supplementary Information Videos S6 and S7.…”

“…Thermic effects are a challenge for any type of measurement [46]. However, the spatial resolution allows on-chip compensation [47][48][49][50]. The camera chip has a dynamic range of 255 a.u.…”

“…The fabrication of the PCS and the surface functionalization was conducted as explained previously [31,47,48,[51][52][53]. Here, we used a PCS with a period length of 370 nm and a depth of 45 nm.…”

“…For a thorough exchange we added 3 mL of liquid. This setup has been described in publications by our workgroup [31,47,48]. The performance effect exerted by the cut-off filter was analyzed by performing a refractometric sweep and step.…”