Abstract
Early and reliable detection of diseases is desirable because it dramatically increases the chance for successful treatment. An increasing number of diseases can be detected at an early stage and monitored due to the presence of certain biomarker molecules in the fluids of the human body (blood, saliva, urine, etc.). Today detection of protein biomarkers is routinely based on immunoassays in centralized labs.
The ability to conduct diagnostic functions on a lab-on-a-chip (LOC) is of great interest. Obtaining analyses results quickly on-site combined with reduced costs and higher throughput of assays are driving forces for LOC technology. Small chip sizes facilitate low sample volumes, allowing better control of molecular interactions close to the sample surface. The quality of transducers, microfluidics and functionalization processes have improved over the last years. However, it has proved challenging to fabricate inexpensive LOC with low limit-of-detection (LOD) and highly reproducible results, particularly in complex biofluids.
Our goal is to address these challenges by developing a multiplexed LOC for detection of biomarkers with improved sensitivity and selectivity compared to state-of-the-art. Laboratory functions are combined on mm2-sized silicon-on-insulator (SOI) chip including biophotonic sensor elements, microfluidic channels and readout circuits. Microfluidic channels guide the transport of fluids containing target biomarkers to the multiplexed photonic sensing elements. These sensitive photonic transducers can detect refractive index changes due to the capture of biomarkers by antibodies immobilized on the sensor surface. By modifying the surface functionalization of the sensing elements, different biomarkers can be detected.
As a proof-of-concept, the sensor is designed for detection of 3 distinct antigens: C-reactive protein, lipocalin 2 and tumor necrosis factor. The main challenge lies within their respective concentrations and LOD and different dynamic ranges for each analyte, varying from ug/ml to pg/ml.
LOC photonic sensor and microfluidic prototypes have been fabricated and characterized. Fig. 1 shows a schematic of the LOC with microfluidics and grating in- and outcoupling, as well as a photo of one of the prototypes. Grating incoupling of light has been introduced to ease alignment and improve optical efficiency. Robust protocols have been established for silicon-on-insulator processing and chemical functionalization (Fig. 2). Numerous transducer designs have been fabricated including ring resonator (RR), Mach Zehnder interferometer (MZI) and photonic crystal (PC) resonators, examples are shown in Fig. 3. The individual transducer designs facilitate different LOD’s and dynamic ranges for each analyte. Measurements of biomarker concentrations in the ug/ml to ng/ml range yield promising results. There is ongoing work on the microfluidics, functionalization and photonic transducer design to improve the LOD to enable measurements of concentrations in the pg/ml range.
The ability to conduct diagnostic functions on a lab-on-a-chip (LOC) is of great interest. Obtaining analyses results quickly on-site combined with reduced costs and higher throughput of assays are driving forces for LOC technology. Small chip sizes facilitate low sample volumes, allowing better control of molecular interactions close to the sample surface. The quality of transducers, microfluidics and functionalization processes have improved over the last years. However, it has proved challenging to fabricate inexpensive LOC with low limit-of-detection (LOD) and highly reproducible results, particularly in complex biofluids.
Our goal is to address these challenges by developing a multiplexed LOC for detection of biomarkers with improved sensitivity and selectivity compared to state-of-the-art. Laboratory functions are combined on mm2-sized silicon-on-insulator (SOI) chip including biophotonic sensor elements, microfluidic channels and readout circuits. Microfluidic channels guide the transport of fluids containing target biomarkers to the multiplexed photonic sensing elements. These sensitive photonic transducers can detect refractive index changes due to the capture of biomarkers by antibodies immobilized on the sensor surface. By modifying the surface functionalization of the sensing elements, different biomarkers can be detected.
As a proof-of-concept, the sensor is designed for detection of 3 distinct antigens: C-reactive protein, lipocalin 2 and tumor necrosis factor. The main challenge lies within their respective concentrations and LOD and different dynamic ranges for each analyte, varying from ug/ml to pg/ml.
LOC photonic sensor and microfluidic prototypes have been fabricated and characterized. Fig. 1 shows a schematic of the LOC with microfluidics and grating in- and outcoupling, as well as a photo of one of the prototypes. Grating incoupling of light has been introduced to ease alignment and improve optical efficiency. Robust protocols have been established for silicon-on-insulator processing and chemical functionalization (Fig. 2). Numerous transducer designs have been fabricated including ring resonator (RR), Mach Zehnder interferometer (MZI) and photonic crystal (PC) resonators, examples are shown in Fig. 3. The individual transducer designs facilitate different LOD’s and dynamic ranges for each analyte. Measurements of biomarker concentrations in the ug/ml to ng/ml range yield promising results. There is ongoing work on the microfluidics, functionalization and photonic transducer design to improve the LOD to enable measurements of concentrations in the pg/ml range.