Two-photon polymerization nanofabrication of ultracompact light scattering spectroscopic probe for detection of pre-cancer in pancreatic cyst.

Pancreatic cancer has one of the worst survival rates of all major cancers, with pancreatic cystic lesions accounting for one in three pancreatic surgeries. The current gold-standard for diagnosis of pancreatic cyst malignancy is based on the endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) procedure, which suffers from a low accuracy in detecting malignancy. Here we present the design and two-photon polymerization based fabrication of refractive and reflective non-contact probes, capable of rapid surveillance of the entire internal cyst surface-an advance over the contact probe we recently developed that allowed, for the first time, reliable evaluation of pancreatic cyst malignant potential in vivo. We employed a novel two-photon polymerization technique, which allows direct laser-writing to an accuracy of tens of nanometers, to fit the probe within the 540 micrometer internal diameter EUS-FNA needle. The newly constructed probes show excellent separation of the illumination and collection beams, essential for proper operation of the spatial gating method. These probes can be used clinically to perform rapid "optical biopsy", ultimately eliminating unnecessary pancreatic surgeries on benign cysts and dangerous delays in surgical removal of malignant cysts, improving patient prognosis and quality of life.