Cyberphysical Integration and Error Recovery for Digital Microfluidic Biochips

The goal of this project is to integrate digital microfluidics systems with thin-film photodetectors in the top plate to realize biochemical target sensing using fluorescence. System control, adaptation, and reconfiguration through software will lead to a general-purpose lab-on-chip computing platform, in the same way as programmable computing devices allow multifunctional capabilities via software on a hardware platform. This level of integration, decision, and controlled reconfigurability will be a significant step forward in clinical diagnostics.

Research is underway on integrating the physical components of this technologythe microfluidic platform and miniaturized sensors, and the cyber componentssoftware for control, decision-making, and adaptation. In particular, hardware/software co-design methods are being developed to ensure that biochips are as versatile as the macro-labs that they are intended to replace. Specific tasks for this project include:

1) Hardware platform development: Research into silicon-based digital microfluidics and integration of optical sensors with digital microfluidics.

2) Cyberphysical system control: Closed-loop operation under software control; error recovery and controller/microfluidics integration; control software for run-time optimization.
3) Decision-tree architectures: Smart decision-making during run-time; adaptive reconfiguration; multi-step bio-molecular recognition strategies.

4) System demonstration: The complete cyberphysical testbed will be demonstrated for the problem of nucleic acid identification on a fabricated chip with detection sites.

During Year 1, the team has studied the integration of a fluorescent detection system in electrowetting chip. In order to detect low input cell concentrations (<104 cell/ml), the digital microfluidic device has designed to maximize DNA copy number per droplet and photodetector (PD) S/N. The initial design to measure the fluorescence in a PD-integrated microfluidic system has been completed. The system includes a power efficient, small external laser, a waveguide for power delivery, and a thin film high sensitivity, low noise Si PD with nitride antireflection (AR) coating to reject the source power. The process recipes have been developed and the photodetector is being fabricated. DNA extraction efficiency has been characterized and a basic polymerase chain reaction (PCR) has been carried out using a single target sequence.

A digital microfluidic device that is dedicated to the initial development of capacitive droplet position sensing and hardware/software integration (i.e., microfluidic device/dynamic droplet routing algorithm) has been fabricated. The fluidic device is capable of manipulating multiple droplets concurrently.

We have provided the first demonstration of the interplay between hardware and software in the biochip platform. Such a demo highlights autonomous cyberphysical operation without any human intervention or human-in-the-loop. We have been able to drive multiple droplets in a fabricated biochip by a pre- programmed assay plan and dynamic adaptation has been accomplished based on feedback of capacitance sensing. Our demo showcases a cyberphysical approach towards closed-loop and sensor feedback-driven biochip operation under program control. We have developed a "physical-aware" system reconfiguration technique that uses sensor data at checkpoints to dynamically reconfigure the biochip.

Award ID: 1135853