Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms.

Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC) platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms.

Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) on a Chip from Whole Blood.

Viral load measurements are an essential tool for the long-term clinical care of hum an immunodeficiency virus (HIV)-positive individuals. The gold standards in viral load instrumentation, however, are still too limited by their size, cost, and sophisticated operation for these measurements to be ubiquitous in remote settings with poor healthcare infrastructure, including parts of the world that are disproportionately affected by HIV infection. The challenge of developing a point-of-care platform capable of making viral load more accessible has been frequently approached but no solution has yet emerged that meets the practical requirements of low cost, portability, and ease-of-use.

On-chip metal/polypyrrole quasi-reference electrodes for robust ISFET operation.

To operate an ion-sensitive field-effect transistor (ISFETs) it is necessary to set the electrolyte potential using a reference electrode. Conventional reference electrodes are bulky, fragile, and too big for applications where the electrolyte volume is small. Several researchers have proposed tackling this issue using a solid-state planar micro-reference electrode or a reference field-effect transistor.

Electronic desalting for controlling the ionic environment in droplet-based biosensing platforms.

The ability to control the ionic environment in saline waters and aqueous electrolytes is useful for desalination as well as electronic biosensing. We demonstrate a method of electronic desalting at micro-scale through on-chip micro electrodes. We show that, while desalting is limited in bulk solutions with unlimited availability of salts, significant desalting of ≥1 mM solutions can be achieved in sub-nanoliter volume droplets with diameters of ∼250 m.

Enhanced biosensing resolution with foundry fabricated individually addressable dual-gated ISFETs.

The adaptation of semiconductor technologies for biological applications may lead to a new era of inexpensive, sensitive, and portable diagnostics. At the core of these developing technologies is the ion-sensitive field-effect transistor (ISFET), a biochemical to electrical transducer with seamless integration to electronic systems. We present a novel structure for a true dual-gated ISFET that is fabricated with a silicon-on-insulator (SOI) complementary metal-oxide-semiconductor process by Taiwan Semiconductor Manufacturing Company (TSMC).

Electrical detection of nucleic acid amplification using an on-chip quasi-reference electrode and a PVC REFET.

Electrical detection of nucleic acid amplification through pH changes associated with nucleotide addition enables miniaturization, greater portability of testing apparatus, and reduced costs. However, current ion-sensitive field effect transistor methods for sensing nucleic acid amplification rely on establishing the fluid gate potential with a bulky, difficult to microfabricate reference electrode that limits the potential for massively parallel reaction detection. Here we demonstrate a novel method of utilizing a microfabricated solid-state quasi-reference electrode (QRE) paired with a pH-insensitive reference field effect transistor (REFET) for detection of real-time pH changes.

Ultralocalized thermal reactions in subnanoliter droplets-in-air.

Miniaturized laboratory-on-chip systems promise rapid, sensitive, and multiplexed detection of biological samples for medical diagnostics, drug discovery, and high-throughput screening. Within miniaturized laboratory-on-chips, static and dynamic droplets of fluids in different immiscible media have been used as individual vessels to perform biochemical reactions and confine the products. Approaches to perform localized heating of these individual subnanoliter droplets can allow for new applications that require parallel, time-, and space-multiplex reactions on a single integrated circuit.

Ultra-localized single cell electroporation using silicon nanowires.

Analysis of cell-to-cell variation can further the understanding of intracellular processes and the role of individual cell function within a larger cell population. The ability to precisely lyse single cells can be used to release cellular components to resolve cellular heterogeneity that might be obscured when whole populations are examined. We report a method to position and lyse individual cells on silicon nanowire and nanoribbon biological field effect transistors.

Silicon nanowires with high-k hafnium oxide dielectrics for sensitive detection of small nucleic acid oligomers.

Nanobiosensors based on silicon nanowire field effect transistors offer advantages of low cost, label-free detection, and potential for massive parallelization. As a result, these sensors have often been suggested as an attractive option for applications in point-of-care (POC) medical diagnostics. Unfortunately, a number of performance issues, such as gate leakage and current instability due to fluid contact, have prevented widespread adoption of the technology for routine use.