SBIR-STTR Award

Advances in clinical imaging technologies have increased the incidental detection rate of cystic pancreatic lesions. However, patients remain at risk due to the lack of a definitive diagnosis that accurately assesses if these cysts are pre-malignant. In the absence of robust diagnostic indicators, clinicians must balance patient safety due to a cystic lesion's rapid and aggressive progression to a malignant pancreatic tumor with the severe financial and physical morbidity and mortality associated with surgical interventions. Retrospective studies have found almost a quarter of surgical interventions to address a pancreatic cyst are unwarranted. A confounder is that retrospective studies have also revealed that when clinicians use a wait-and-see approach, up to a quarter of patients receive surgical resection too late. The dual-edged nature of this process highlights the need for better early-stage diagnostic tools. There remains an unmet clinical need for diagnostic information that can accurately stratify the risk associated with pre-cancerous, fluid-filled pancreatic lesions that are commonly the first sign of concern. Currently, clinicians can obtain fluid from incidentally detected pancreatic cysts for chemical analysis of disease- associated molecular markers. Pancreatic cyst fluid samples are most often highly viscous, making it difficult to aliquot, and can be very limited in volume depending on the size of cyst. Furthermore, available biomarker assays lack sensitivity, can have long turnaround times, and require high sample volumes. These traits limit the amount and quality of information from single pancreatic cyst fluid samples. Clinicians must rely on their unique experiences when choosing between appropriate analyses, which further confuses attempts at standardization of clinical care. Amplified Sciences has developed a robust assay platform to analyze low-volume (down to 1 µL) clinical pancreatic cyst fluid samples for protease activity to distinguish non-mucinous from mucinous pancreatic cyst populations. In this proposal, Amplified Sciences is expanding the platform to provide higher content diagnostic information about the malignant potential of the mucinous pancreatic cyst population. Amplified Sciences assay and detection platforms are adaptable to new biomarker targets. This proposal aims to create a multidimensional assay panel that accurately determines the risk of pancreatic cysts progression to cancer. A combination of three (3) markers under investigation by collaborators at Alaunus Biosciences and UCSF show promise to stratify the grade of dysplasia in a limited number of clinical mucinous pancreatic cyst samples. This proposal will 1) validate the capacity of these markers to distinguish low- from high-grade dysplasia in retrospective mucinous clinical samples and 2) translate low-volume assays for these markers into CLIA-ready protocols to enable stacking of assays on individual samples. Upon completion, a novel assay panel will be available that uses minimal cyst fluid volumes to quantitate the validated biomarkers, comprising a new method for clinicians to maximize accurate diagnostic information from precious clinical samples with rapid turnaround.

Public Health Relevance Statement:
NARRATIVE The high morbidity and mortality of pancreatic cancer can easily be attributed to the late stage at which clinicians are able to properly diagnose this disease due to a dearth of early-stage tools to accurately grade dysplasia. With an increasing rate of pancreatic cysts being incidentally discovered through routine imaging analyses, there is a growing unmet need for clinical diagnostics that can diagnose patients actually at risk while protecting the non-malignant population from burdensome, unnecessary treatment. This proposal seeks to produce a multidimensional assay panel that will accurately inform clinicians decision-making using single, low-volume (down to 1 µL) clinical samples in an effort to reduce unnecessary surgical interventions.

Project Terms:
Archives; Biological Assay; Assay; Bioassay; Biologic Assays; Biological Sciences; Biologic Sciences; Bioscience; Life Sciences; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Clinical Distribution; Confusion; Confusional State; Mental Confusion; Cyst; Decision Making; Diagnosis; Disease; Disorder; Dyes; Coloring Agents; Environment; Enzymes; Enzyme Gene; Equilibrium; balance; balance function; Fluorescence; Freezing; Laboratories; Magnetic Resonance Imaging; MR Imaging; MR Tomography; MRI; MRIs; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; NMR Imaging; NMR Tomography; Nuclear Magnetic Resonance Imaging; Zeugmatography; Methods; Morbidity - disease rate; Morbidity; mortality; Mucous body substance; Mucus; mucous; Pancreas; Pancreatic; Pancreatic Cyst; Pancreas Cyst; pancreatic neoplasm; Pancreas Neoplasms; Pancreas Tumor; Pancreatic Tumor; pancreatic neoplasia; Patients; Pepsinogen C; Pepsinogen II; Progastricsin; Peptide Hydrolases; Esteroproteases; Peptidases; Protease Gene; Proteases; Proteinases; Proteolytic Enzymes; Peroxidases; Hemi-Myeloperoxidase; Myeloperoxidase; Proteins; Publications; Scientific Publication; Retrospective Studies; Risk; Science; Sensitivity and Specificity; Raman Spectrum Analysis; IR/UV/Raman Spectroscopy; Raman Spectroscopy; Raman imaging; Raman spectrometry; Standardization; Survival Rate; Testing; Time; Translating; Viscosity; gastricsin; pepsin C; Leukocyte Elastase; Granulocyte Elastase; Lysosomal Elastase; Neutrophil Elastase; PMN Elastase; Polymorphonuclear Leukocyte Elastase; Measures; Blinded; cancer progression; neoplasm progression; neoplastic progression; tumor progression; Label; improved; specimen collection; sample collection; Site; Surface; Benign; Clinical; Malignant; Malignant - descriptor; Phase; Biochemical; Chemicals; Evaluation; Lesion; Individual; enzyme activity; Collaborations; fluid; liquid; Liquid substance; clinical diagnosis; Inflammatory; Dysplasia; dyscrasia; tool; Malignant neoplasm of pancreas; Malignant Pancreatic Neoplasm; Pancreas Cancer; Pancreatic Cancer; pancreatic malignancy; Diagnostic; Nature; Specimen; Research Specimen; Unnecessary Surgery; Investigation; Dimensions; Protocols documentation; Protocol; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; dimer; experience; Performance; cohort; trait; Rhodamine; Cyst Fluid; novel; Elastases; Reporting; Excision; Abscission; Extirpation; Removal; Surgical Removal; resection; Sampling; Pancreatic enzyme; pancreas enzyme; patient safety; preventing; prevent; tripeptidyl aminopeptidase; tripeptidyl peptidase; Address; Aliquot; Cystic Lesion; Detection; Mucinous; premalignant; precancer; precancerous; Resolution; resolutions; Non-Malignant; nonmalignant; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; validations; Process; Development; developmental; Image; imaging; Imaging technology; Population; prospective; translation assay; clinical care; activity marker; inflammation marker; inflammatory marker; molecular biomarker; molecular marker; bio-markers; biologic marker; biomarker; Biological Markers; disease diagnosis; clinical decision-making; operations; operation; accurate diagnosis; dimensional analysis; targeted biomarker; biomarker array; marker panel; biomarker panel; unnecessary treatment; stratify risk; risk stratification; medical diagnostic; clinical diagnostics; clinical imaging; routine imaging; clinical decision support; marker validation; biomarker validation; pancreatic cystic lesions; pancreatic cystic neoplasms; pancreatic cystic tumors; Pancreatic cystic neoplasia; High grade dysplasia; detection procedure; detection technique; detection method; detection system; detection platform; accurate diagnostics; diagnostic tool; diagnostic value; diagnostic ability; diagnostic capability; diagnostic power; diagnostic utility; technology platform; technology system