OT-LUNA blog-Early and reliable detection of organ injury biomarkers using NANOenhanced SPRi technology

Jennifer Miller and Lance Li
Luna’s Nanomaterials Group

http://lunainc.com/early-reliable-detection-organ-injury-biomarkers-nanoenhanced-spri-technology/

What are biomarkers and why are they important? 

Biomarkers are measurable indicators of the presence and extent of a disease process in the body, reflecting an interaction between a biological system in the body and a potential hazard. These indicators can be a number of different substances including nucleic acids, proteins and small molecules (Figure 1). Testing for the presence of certain biomarkers can provide important information for identifying disease and the extent to which it has progressed.  This information can be critical in making timely and effective treatment decisions.

Figure 1. Biomarkers and their organ-specific release siteshttp://www.nature.com/nrcardio/journal/v9/n8/fig_tab/nrcardio.2012.60_F1.html

Biomarkers in detection and treatment of multiple organ injury
Major organ injuries such as liver, kidney, heart and lung injuries can lead to high morbidity and mortality in critically ill patients. Safety biomarkers have been suggested to have predictive values before tissue injury for specific organs becomes irreversible. Identification of such biomarkers in clinical samples would improve the early detection of organ injury, help identify appropriate preventive or curative strategies, preventing organ injury into organ failure, and improving the quality of life. It has been demonstrated that detection using a panel of biomarkers, provides greater sensitivity and specificity for assessing the presence and extent of a disease or injury process than with the use of a single biomarker. A highly accurate blood-based diagnostic panel can be developed from a reasonable number of individual serum biomarkers that are relatively weak classifiers when used singly.
NANOenhanced SPRi diagnostic platform
Luna is developing a nanotechnology empowered surface plasmon resonance imaging platform (NANOenhanced SPRi) for performing the ideal assay to simultaneously detect a panel of biomarkers for the diagnosis of organ injury. The novel NANOenhanced sensing array incorporates several important features that need to function in a concerted way leading to significantly improved diagnostic sensitivity and specificity. The assay minimizes non-specific protein, cell, and lipid binding reducing the background signal and permitting the direct testing of plasma, blood, urine, saliva and other body fluids. Another important advantage is the use of nanotechnology for signal amplification.  It provides high diagnostic accuracy, is non-invasive (tests body fluids), uses a small sample size (less than 100 μL), has a fast turnaround time (within 30 minutes) and can test for multiple biomarkers using one sample (Figure 2). The sensing chips are customizable to test tens to hundreds of biomarkers simultaneously that could be proteins, DNAs, microRNAs, small molecules and their combinations. The sensing chips are premade for the use with any SPRi platform (Figure 3).This platform can be further used to develop assays for the detection of a variety of biomarker panels known to be indicative of almost all diseases, providing the timely and reliable results critical for successful patient treatment plans.  The NANOenhanced SPRi technique is superior to current leading quantitative assay methods such as MALDI-MS, PCR, microarray, and ELISA.

Figure 2. NANOenhanced SPRi Diagnostic Platform

Figure 3. Operation diagram of the NANOenhanced SPRi diagnostic platform – sensing chips are customized for detecting selected panels of biomarkers and pre-prepared for use with any SPRi platforms.

As an example, Luna’s NANOenhanced SPRi Multiplex Biomarker Assay for Organ Injury demonstrates femtogram sensitivity and multiplex capabilities with the detection of three biomarkers, Mi1222, KIM-1 and HMGB-1 (protein biomarkers specific to liver and kidney injury) in a single sample (Figure 4). The sensing arrays were able to show distinct binding signals to corresponding biomarkers. The assay detected KIM-1 biomarker at fg/mL level. Detection requires a run time of less than 30 minutes, providing important clinical information rapidly.

Figure 4. NANOenhanced SPRi Assay demonstrates multiplex detection of three biomarkers, MiR122, KIM-1 and HMGB-1 in a single sample.

Luna is presenting (an oral presentation and a poster) at the 2015 NanoTechnology for Defense (NT4D) conference – the 13th Annual Nano for Defense Conference – Transitioning Emerging Technologies (NT4D), 16 – 19 November 2015 in City of Industry, CA. This event was initiated and is supported by the Air Force Research Laboratory, Army Research Laboratory, the Office of Naval Research, the Defense Threat Reduction Agency, and the Defense Advanced Research Projects Agency. NT4D is the premier event addressing emerging nanoenabled technologies for defense.