Molecular analyses of cancer cells are essential in establishing diagnoses and guiding available treatments. Conventional tissue biopsies, while providing key information on tissue architecture, are associated with morbidity and high cost and therefore are not performed as frequently as would be clinically desirable. An alternative to cutting core biopsy guns are fine needle aspirations (FNAs), which can be performed with minimal intervention and allow for less invasive and/or repeated sampling from small lesions. However, workup of FNA specimens remains challenging using conventional cytology and immunohistochemistry. To address these barriers, Aikili Biosystems seeks to enable same-day diagnostic workup of FNA samples using a proprietary FAST assay and automated image cytometer. A key component of Aikili's technology is our proprietary cell cycling method (FAST), which builds upon and expands previous assay capabilities (4- channel multiplexing) to over 20-40 biomarkers; it is coupled with our image cytometer, a stand-alone diagnostic platform capable of automated cancer cell classification in <2 hours. Building upon initial development and pre-clinical validation, in Aim 1, we will validate FAST antibody probes in >15 cancer markers, integrate sample processing with Aikili's cytometry system and analyze associated images using the device. In Aim 2, we will evaluate the benefit of the integrated technology for rapid, same-day analysis of clinical samples, specifically lymphoma FNA samples (n = 40) stained with FAST-linker modified antibody probes. Phase I will be deemed successful when Aikili's system reliably detects and classifies lymphoma cells compared to gold standards. Successful completion of Phase I will lay the foundation for a Phase II application for clinical testing and manufacture of cytometry systems and commercial cartridges for multiple cancers. This platform has potential to transform cellular diagnostics and pathology workflows through rapid, same-day analyses of minimally invasive FNAs; its robust analyses of pharmacodynamic markers has potential to enable development of new, clinically meaningful biomarkers that can be used to advance drug development. Public Health Relevance Statement We have developed a standalone, automated diagnostic platform that allows deep, single cell profiling of scant cellular samples from multiple cancer types by profiling dozens of markers per cell. Our approach aims to transform cellular diagnostics through rapid, same-day analyses of clinical samples, as well as augment pathology workflows by greatly expanding on the capabilities of conventional cytology. By enabling robust analyses of pharmacodynamic markers, our platform also has potential to play a pivotal role in rapidly accruing patients into cancer clinical trials, assessing therapeutic efficacy and/or re-staging disease.
Project Terms: Algorithms ; Antibodies ; Architecture ; Engineering / Architecture ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biopsy ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Cell Cycle ; Cell Division Cycle ; Cell Line ; CellLine ; Strains Cell Lines ; cultured cell line ; Cell Survival ; Cell Viability ; Cells ; Cell Body ; Classification ; Systematics ; Cytology ; Data Analyses ; Data Analysis ; data interpretation ; Diagnosis ; Disease ; Disorder ; Eligibility Determination ; Eligibility ; Protocol Screening ; Flow Cytometry ; Flow Cytofluorometries ; Flow Cytofluorometry ; Flow Microfluorimetry ; Flow Microfluorometry ; flow cytophotometry ; Fluorochrome ; Foundations ; Goals ; Gold ; Guns ; gun ; Hydrogen Peroxide ; H2O2 ; Hydroperoxide ; Immunohistochemistry ; Immunohistochemistry Cell/Tissue ; Immunohistochemistry Staining Method ; Light ; Photoradiation ; lymph nodes ; Lymph Node Reticuloendothelial System ; Lymph node proper ; Lymphatic nodes ; lymph gland ; lymphnodes ; Lymphoid Tissue ; Lymphatic Tissue ; Lymphoma ; Germinoblastic Sarcoma ; Germinoblastoma ; Malignant Lymphoma ; Reticulolymphosarcoma ; Methods ; Morbidity - disease rate ; Morbidity ; Pathology ; Patients ; Play ; Reagent ; Epidermal Growth Factor Receptor ; EGF Receptor ; EGFR ; ERBB Protein ; Epidermal Growth Factor Receptor Kinase ; Epidermal Growth Factor Receptor Protein-Tyrosine Kinase ; Epidermal Growth Factor-Urogastrone Receptors ; HER1 ; TGF-alpha Receptor ; Transforming Growth Factor alpha Receptor ; Urogastrone Receptor ; c-erbB-1 ; c-erbB-1 Protein ; erbB-1 ; erbB-1 Proto-Oncogene Protein ; erbBl ; proto-oncogene protein c-erbB-1 ; Role ; social role ; Sensitivity and Specificity ; Stains ; Staining method ; Technology ; Thyroid Nodule ; Thyroid Gland Nodule ; Time ; Tissues ; Body Tissues ; CD3 Antigens ; CD3 ; CD3 Complex ; CD3 molecule ; OKT3 antigen ; T3 Antigens ; T3 Complex ; T3 molecule ; Custom ; Cell Size ; Cyclin D1 ; CCND1 Protein ; G1/S-Specific Cyclin D1 ; PRAD1 Protein ; Proto-Oncogene Proteins c-bcl-1 ; bcl-1 Proto-Oncogene Products ; bcl-1 Proto-Oncogene Proteins ; bcl1 Proto-Oncogene Proteins ; c-bcl-1 Proteins ; cyclin D ; improved ; Procedures ; Clinical ; Phase ; Chemicals ; Lesion ; Epithelial ; ERBB2 gene ; ERBB2 ; HER -2 ; HER-2 ; HER2 ; HER2 Genes ; HER2/neu ; NEU Oncogene ; NEU protein ; Oncogene ErbB2 ; TKR1 ; c-erbB-2 ; c-erbB-2 Genes ; c-erbB-2 Proto-Oncogenes ; erbB-2 Genes ; herstatin ; neu Genes ; Cytopathology ; Cytology and Pathology ; Image Cytometry ; Staging ; Malignant Cell ; cancer cell ; Diagnostic ; Research Specimen ; Specimen ; Hour ; protein profiling ; System ; Head and Neck ; Head and neck structure ; palpable disease ; Palpable ; interest ; Performance ; success ; fluorophore ; Speed ; novel ; Devices ; Cytometry ; Sampling ; drug development ; Intervention Strategies ; interventional strategy ; Intervention ; cancer care ; Cyclooctenes ; Core Needle Biopsy ; Core Biopsy ; B220 ; CD45 ; GP180 ; LY5 ; PTPRC ; T200 ; PTPRC gene ; ACVRL1 ; ACVRLK1 ; ALK-1 ; Activin A Receptor, Type II-Like Kinase 1 Gene ; Activin Receptor-Like Kinase 1 Gene ; HHT2 ; ORW2 ; SKR3 ; ACVRL1 gene ; CD8 ; CD8B ; CD8B1 ; LYT3 ; CD8B1 gene ; CD19 ; CD19 gene ; Bp35 ; CD20 ; Leu-16 ; MS4A1 ; MS4A2 ; MS4A1 gene ; Address ; CD30 ; KI-1 ; TNFRSF8 ; TNFRSF8 gene ; FNA ; Fine Needle Aspirate ; Fine-Needle Aspiration ; Fine needle aspiration biopsy ; Consent ; Detection ; Harvest ; Molecular Analysis ; Molecular Diagnosis ; Molecular Fingerprinting ; molecular profile ; molecular signature ; Molecular Profiling ; MUC-1 ; MUC1 ; MUC1 gene product ; Muc1 Mucin ; Mucin 1 ; Mucin 1 protein ; research clinical testing ; Clinical Evaluation ; Clinical Testing ; clinical test ; Validation ; Process ; Development ; developmental ; Image ; imaging ; pre-clinical ; preclinical ; cost ; Treatment Efficacy ; intervention efficacy ; therapeutic efficacy ; therapy efficacy ; scale up ; cancer type ; Stress Tests ; Coupled ; clinical application ; clinical applicability ; novel diagnostics ; new diagnostics ; next generation diagnostics ; minimally invasive ; standard of care ; Biological Markers ; bio-markers ; biologic marker ; biomarker ; Institutional Review Boards ; IRB ; IRBs ; image guided ; image guidance ; pharmacodynamic biomarker ; pharmacodynamic marker ; cancer biomarkers ; cancer markers ; protein biomarkers ; protein markers ; cancer clinical trial ; oncology clinical trial ; molecular diagnostics ; experimental study ; experiment ; experimental research ; multidimensional data ; high dimensional data ; multidimensional datasets ; Visualization ; Lymphoma cell ; diagnostic platform ; diagnostic system ;
