Surface-Enhanced Raman Spectroscopy-Based Label-Free Insulin Detection at Physiological Concentrations for Analysis of Islet Performance

Abstract

Label-free optical detection of insulin would allow in vitro assessment of pancreatic cell functions in their natural state and expedite diabetes-related clinical research and treatment, however no existing method has met these criteria at physiological concentrations. Using spatially-uniform 3D gold-nanoparticle sensors, we have demonstrated surface-enhanced Raman sensing of insulin in the secretions from human pancreatic islets under low and high glucose environments without the use of labels such as antibodies or aptamers. Label-free measurements of the islet secretions showed excellent correlation among the ambient glucose levels, secreted insulin concentrations, and measured Raman-emission intensities. When excited at 785 nm, plasmonic hotspots of the densely-arranged 3D gold-nanoparticle pillars as well as strong interaction between sulphide linkages of the insulin molecules and the gold nanoparticles produced highly sensitive and reliable insulin measurements down to 100 pM. The sensors exhibited a dynamic range of 100 pM to 50 nM with an estimated detection limit of 35 pM, which covers the reported concentration range of insulin observed in pancreatic cell secretions.The sensitivity of this approach is approximately four orders of magnitude greater than previously reported results using label-free optical approaches, and it is much more costeffective than immunoassay-based insulin detection widely used in clinics and laboratories. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3 Hormones are chemical messengers that control a wide variety of functions in the human body. Maintaining adequate hormone levels is extremely important for human health and disruption to these levels can result in life-debilitating conditions. Simple and easy measurements of hormonal secretions ex vivo or in vivo are essential for implementing next generation biosensors, allowing convenient monitoring of health and early disease detection.One of the most prevalent diseases resulting from hormonal dysfunction is diabetes, which arises from a disruption in the release of insulin in the body. 1-2 Insulin is a peptide hormone which is secreted by beta cells, one of five primary cell-types which populate pancreatic cellular clusters known as islets. The concentration of insulin secreted from beta cells in plasma has been reported to vary between 100 pM (fasting) and 2 nM (about 1 hour after glucose intake) in non-diabetic individuals. [3][4] In diabetic individuals, functional damage to the beta cells reduces or inhibits their ability to release insulin. One of the leading methodologies for treatment of type-1 diabetes is pancreatic islet transplantation, where healthy islets harvested from deceased donors are transplanted into diabetic patients. [5][6] Since the number of donors is limited, methodologies that can improve the efficiency and succe...

High index contrast photonic platforms for on-chip Raman spectroscopy

“…The results presented in this paper will help to further improve the sensitivity of NWERS sensors. Along with other integrated photonics functionalities, these on-chip Raman sensors can be employed in many interesting application such as the detection of VOCs [28] in ambient air or sensing of bio-analytes in physiological concentration [29,30].…”

Aluminum Metasurface with Hybrid Multipolar Plasmons for 1000-Fold Broadband Visible Fluorescence Enhancement and Multiplexed Biosensing

“…When insulin-binding aptamers were tagged with three different fluorophores, insulin adsorbed on the nDISC metasurface was robustly and consistently detected at all three different wavelengths (center excitation wavelengths: 488 nm, 555 nm and 647 nm) in the visible range (Figure 5c-d). 36 Detection of insulin is crucial for clinical diabetes treatment and management such as islet transplantation 24 or prevention of insulin-overdose in diabetic patients. 37 We also obtained linear concentration-dependent sensing response with metasurface-enhanced fluorescence for insulin concentrations ranging from 1 nM to 100 nM (Figure 5e) consistently for all three wavelengths, suggesting that the metasurface can be capable of simultaneous detection of biomarkers at different wavelengths in the visible regime.…”

High-performance flexible metal-on-silicon thermocouple

“…In addition to being implementable in flexible forms, our simulations and first-order analysis suggest chrome-silicon unit cells can be scaled down to 5×5 µm 2 , and adjacent cells can be spaced as close as 1 µm. We expect the design approach and thermocouple platforms demonstrated in this work will be widely utilized in micro-/nanoscale thermometry and thermal mapping specially relevant to plasmonic sensors 11 , 41 – 44 , optoelectronics thermal studies and characterizations 45 , and various thermal sensors for biological and physiological analysis 7 , 8 , 10 .…”