Resolving SPARC–HSA binding kinetics with an ultrasensitive photonic sensor based on bound states in the continuum

Journal Article · Wed Jul 16 00:00:00 EDT 2025 · Biosensors and Bioelectronics

DOI:https://doi.org/10.1016/j.bios.2025.117754· OSTI ID:3012250

Miranda, Bruno ^[1]; Mele, Vincenza ^[2]; Seifalinezhad, Aida ^[3]; Zito, Gianluigi ^[1]; Schwartzberg, Adam ^[4]; Mocella, Vito ^[1]; Rendina, Ivo ^[1]; Lamberti, Annalisa ^[2]; Sanità, Gennaro ^[1]; Romano, Silvia ^[1]

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1. National Research Council (CNR), Naples (Italy)
2. Univ. of Naples Federico II (Italy)
3. National Research Council (CNR), Naples (Italy); Univ. degli Studi di Napoli Parthenope (Italy)
4. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Molecular Foundry

Secreted protein acidic and rich in cysteine (SPARC) is critical in cell-matrix interactions and tissue remodeling. It influences tumor progression through its affinity for human serum albumin (HSA) - the most abundant plasma protein, which also plays a crucial role in drug delivery. Strong molecular binding leads to a dissociation constant K_D in the nanomolar range. Thus, determining K_D requires detecting sub-nanomolar concentrations with ultrasensitive methods. This may be crucial for elucidating the nature of SPARC-HSA binding, as their interaction remains a subject of debate. Capturing these interactions accurately requires a platform capable of resolving rapid binding kinetics at extremely low analyte concentrations. In this work, we report on a microfluidics-integrated photonic nanostructure that supports bound states in the continuum (BICs) and is optimized for studying the fast kinetics of high-affinity protein-protein interactions. The unprecedented capability of detecting sub-nanomolar concentrations allows quantifying K_D between SPARC and HSA beyond the state of the art. We leverage an all-dielectric photonic crystal slab (PhCS) sustaining two BIC branches arising from gapped Dirac cone dispersion. HSA is covalently immobilized on the PhCS bonded to a PDMS microfluidic chamber. SPARC dissociation is carried out using PBS buffer (pH 7.4), ensuring complete protein release through precise control of the flow rate and continuous spectral monitoring of the BICs. The measured K_D = 8.2±0.8 nM confirms the strong affinity of SPARC for HSA. This study highlights the potential of BIC-based sensing as a versatile tool for investigating protein interactions. These results also have implications for the optimization of drug delivery systems and cancer treatment strategies.

• Research Organization: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)
• Grant/Contract Number: AC02-05CH11231
• OSTI ID: 3012250
• Journal Information: Biosensors and Bioelectronics, Journal Name: Biosensors and Bioelectronics Vol. 288; ISSN 0956-5663
• Publisher: Elsevier
• Country of Publication: United States
• Language: English

Related Subjects

Albumin
Bound states in the continuum
Dissociation constant
Photonic crystals
SPARC