A multiplexable, microfluidic platform for the rapid quantitation of a biomarker panel for early ovarian cancer detection at the point-of-care.
Point-of-care (POC) diagnostic platforms have the potential to enable low-cost, large-scale screening. As no single biomarker is shed by all ovarian cancers, multiplexed biomarker panels promise improved sensitivity and specificity to address the unmet need for early detection of ovarian cancer. We have configured the programmable bio-nano-chip (p-BNC)-a multiplexable, microfluidic, modular platform-to quantify a novel multi-marker panel comprising CA125, HE4, MMP-7, and CA72-4. The p-BNC is a bead-based immunoanalyzer system with a credit-card-sized footprint that integrates automated sample metering, bubble and debris removal, reagent storage and waste disposal, permitting POC analysis. Multiplexed p-BNC immunoassays demonstrated high specificity, low cross-reactivity, low limits of detection suitable for early detection, and a short analysis time of 43 minutes. Day-to-day variability, a critical factor for longitudinally monitoring biomarkers, ranged between 5.4% and 10.5%, well below the biologic variation for all four markers. Biomarker concentrations for 31 late-stage sera correlated well (R(2) = 0.71 to 0.93 for various biomarkers) with values obtained on the Luminex platform. In a 31 patient cohort encompassing early- and late-stage ovarian cancers along with benign and healthy controls, the multiplexed p-BNC panel was able to distinguish cases from controls with 68.7% sensitivity at 80% specificity. Utility for longitudinal biomarker monitoring was demonstrated with prediagnostic plasma from 2 cases and 4 controls. Taken together, the p-BNC shows strong promise as a diagnostic tool for large-scale screening that takes advantage of faster results and lower costs while leveraging possible improvement in sensitivity and specificity from biomarker panels.
Department of Chemistry, Rice University, Houston, Texas.
Basil H
BH
Shadfan
Department of Chemistry, Rice University, Houston, Texas. Department of Bioengineering, Rice University, Houston, Texas.
Archana R
AR
Simmons
Department of Chemistry, Rice University, Houston, Texas. Department of Bioengineering, Rice University, Houston, Texas.
Glennon W
GW
Simmons
Department of Chemistry, Rice University, Houston, Texas. Department of Bioengineering, Rice University, Houston, Texas.
Andy
A
Ho
Department of Chemistry, Rice University, Houston, Texas. Department of Bioengineering, Rice University, Houston, Texas.
Jorge
J
Wong
Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Karen H
KH
Lu
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Robert C
RC
Bast
Department of Chemistry, Rice University, Houston, Texas. Department of Bioengineering, Rice University, Houston, Texas. mcdevitt@nyu.edu.
John T
JT
McDevitt
D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood; D001331:Automation; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D002138:Calibration; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000295:instrumentation* / Q000379:methods; D020783:Matrix Metalloproteinase 7 / Q000097:blood; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods; D036103:Nanotechnology / Q000379:methods; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis*; D019095:Point-of-Care Systems; D011506:Proteins / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000081102:WAP Four-Disulfide Core Domain Protein 2
D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C083825:CA-72-4 antigen; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7