Material-Intrinsic NIR-Fluorescence Enables Image-Guided Surgery for Ceramic Fracture Removal.

Hip arthroplasty effectively treats advanced osteoarthritis and is therefore entitled as "operation of the 20th century." With demographic shifts, the USA alone is projected to perform up to 850 000 arthroplasties annually by 2030. Many implants now feature a ceramic head, valued for strength and wear resistance. Nonetheless, a fraction, up to 0.03% may fracture during their lifespan, demanding complex removal procedures. To address this, a radiation-free, fluorescence-based image-guided surgical technique is presented. The method uses the inherent fluorescence of ceramic implant materials, demonstrated through chemical and optical analysis of prevalent implant types. Specifically, Biolox delta implants exhibited strong fluorescence around 700 nm with a 74% photoluminescence quantum yield. Emission tails are identified extending into the near-infrared (NIR-I) biological transparency range, forming a vital prerequisite for the label-free visualization of fragments. This ruby-like fluorescence could be attributed to Cr within the zirconia-toughened alumina matrix, enabling the detection of even deep-seated millimeter-sized fragments via camera-assisted techniques. Additionally, fluorescence microscopy allowed detection of µm-sized ceramic particles, enabling debris visualization in synovial fluid as well as histological samples. This label-free optical imaging approach employs readily accessible equipment and can seamlessly transition to clinical settings without significant regulatory barriers, thereby enhancing the safety, efficiency, and minimally invasive nature of fractured ceramic implant removal procedures.

Signal Amplification and Near-Infrared Translation of Enzymatic Reactions by Nanosensors.

Enzymatic reactions are used to detect analytes in a range of biochemical methods. To measure the presence of an analyte, the enzyme is conjugated to a recognition unit and converts a substrate into a (colored) product that is detectable by visible (VIS) light. Thus, the lowest enzymatic turnover that can be detected sets a limit on sensitivity. Here, we report that substrates and products of horseradish peroxidase (HRP) and ß-galactosidase change the near-infrared (NIR) fluorescence of (bio)polymer modified single-walled carbon nanotubes (SWCNTs). They translate a VIS signal into a beneficial NIR signal. Moreover, the affinity of the nanosensors leads to a higher effective local concentration of the reactants. This causes a non-linear sensor-based signal amplification and translation (SENSAT). We find signal enhancement up to ≈120x for the HRP substrate p-phenylenediamine (PPD), which means that reactions below the limit of detection in the VIS can be followed in the NIR (≈1000 nm). The approach is also applicable to other substrates such as 3,3'-5,5'-tetramethylbenzidine (TMB). An adsorption-based theoretical model fits the observed signals and corroborates the sensor-based enhancement mechanism. This approach can be used to amplify signals, translate them into the NIR and increase sensitivity of biochemical assays.

Near-Infrared Fluorescent Biosensors Based on Covalent DNA Anchors.

Semiconducting single-walled carbon nanotubes (SWCNTs) are versatile near-infrared (NIR) fluorophores. They are noncovalently modified to create sensors that change their fluorescence when interacting with biomolecules. However, noncovalent chemistry has several limitations and prevents a consistent way to molecular recognition and reliable signal transduction. Here, we introduce a widely applicable covalent approach to create molecular sensors without impairing the fluorescence in the NIR (>1000 nm). For this purpose, we attach single-stranded DNA (ssDNA) via guanine quantum defects as anchors to the SWCNT surface. A connected sequence without guanines acts as flexible capture probe allowing hybridization with complementary nucleic acids. Hybridization modulates the SWCNT fluorescence and the magnitude increases with the length of the capture sequence (20 > 10 ≫ 6 bases). The incorporation of additional recognition units via this sequence enables a generic route to NIR fluorescent biosensors with improved stability. To demonstrate the potential, we design sensors for bacterial siderophores and the SARS CoV-2 spike protein. In summary, we introduce covalent guanine quantum defect chemistry as rational design concept for biosensors.

Biosensing with Fluorescent Carbon Nanotubes.

Biosensors are powerful tools for modern basic research and biomedical diagnostics. Their development requires substantial input from the chemical sciences. Sensors or probes with an optical readout, such as fluorescence, offer rapid, minimally invasive sensing of analytes with high spatial and temporal resolution. The near-infrared (NIR) region is beneficial because of the reduced background and scattering of biological samples (tissue transparency window) in this range. In this context, single-walled carbon nanotubes (SWCNTs) have emerged as versatile NIR fluorescent building blocks for biosensors. Here, we provide an overview of advances in SWCNT-based NIR fluorescent molecular sensors. We focus on chemical design strategies for diverse analytes and summarize insights into the photophysics and molecular recognition. Furthermore, different application areas are discussed-from chemical imaging of cellular systems and diagnostics to in vivo applications and perspectives for the future.