Securing Biochemical Samples Using Molecular Barcoding on Digital Microfluidic Biochips*

Microfluidic biochips are being adopted today in point-of-care diagnostics, e.g., COVID-19 testing; therefore, it is critical to ensure integrity of bio-sample before bioassays are run on-chip. A security technique called molecular barcoding was recently proposed to thwart sample-forgery attacks in DNA forensics. Molecular barcoding refers to addition of unique DNA molecules in bio-samples, and the sequence of the added DNA sample serves as a distinct “barcode” for the sample. The existence of the added molecule can be validated using polymerase chain reaction (PCR) and gel electrophoresis. However, this security solution has several limitations: (1) the lack of robustness of the barcode molecules when they are added to other genomic DNA (e.g., samples collected for diagnostics); (2) the need for special bulk instrumentation for validation; (3) the need for human intervention during the overall process. To overcome the limitations, we design a set of robust molecular barcodes that can be validated using both traditional polymerase chain reaction and loop mediated isothermal amplification (LAMP). The validation using LAMP can be executed on a small-in-size and portable digital microfluidic biochip (DMFB). Our LAMP workflow includes a color-changing visual indicator for simple, rapid identification of the barcode existence in solutions. We first demonstrate the proposed security workflow using benchtop techniques. Next, we fabricate a printed circuit board (PCB)-based DMFB with heaters and demonstrate, for the first time, the LAMP assay on a DMFB.