Developing Fully-Integrated Biosensing Systems on the Laboratory Benchtop
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abstract
Fully-integrated biosensing systems that detect the presence, absence, and quantity of biomolecules (nucleic acids and proteins) in clinical samples have a wide range of applications in clinical diagnosis of cancers, infectious diseases, and hereditary diseases. Furthermore, handheld and inexpensive biosensors that can be operated with a high degree of automation by novice users make it possible for these systems to be applied to point-of-care (POC) settings where the current state-of-the-art diagnostic tests, designed for centralized laboratories, are not applicable. In order to develop handheld, automated, and inexpensive biosensing systems applicable to the point-of-care, it is essential to combine multiple devices for sample preparation and biomolecular detection on the same platform. This requires multiple materials and structures having a wide range of properties and length-scales to be integrated on the same platform. Furthermore, translation of such multi-material systems from the laboratory to the market indicates the need for inexpensive, rapid, and scalable fabrication methods for creating tunable materials and structure. We have developed an integrated fabrication process for creating all-electrical biosensing platforms using methods available on the laboratory benchtop. In order to create electrodes that are structurally tunable from the 10 nm to the 10 mm length-scale and meet the conductivity demands of sample preparation and biosensing devices, we have combined methods including craft cutting, ink-jet printing, self-assembly, electroless deposition, and electrodeposition to deposit and pattern application-specific materials on polymer substrates. In addition, we have used shape memory polymers to further tune the properties of the patterned electrodes such as surface texture, film thickness, and conductivity. Materials characterization results obtained using techniques including scanning electron microscopy, atomic force microscopy, and four-point-probe method indicate that the fabrication method results in electrodes of the appropriate configuration (micro-coils, interdigitated electrodes, electrode arrays), surface texture (tunable from tens of nanometer to tens of microns), and conductivity (>5% of the bulk) for use in an all-electrical biosensing platform. Using the abovementioned fabrication methods, we have developed three classes of devices for bacterial lysis, magnetic manipulation of cells and biomolecules, and detection of nucleic acids. Bacterial lysis devices that include an interdigitated array of microelectrodes decorated with electrodeposited three-dimensional nano-pillars offer high efficiency lysis (> 95%) at low applied potentials (4 V). The magnetic manipulation devices containing on-polymer magnetic coils coupled with a ferromagnetic capture layer generate forces required for manipulating super-paramagnetic microbeads (1-10 pN) at low applied currents (< 50 mA). Furthermore, we have created a fully-integrated electro-fluidic device for electrochemical detection of nucleic acids. Given that all of these devices are created using the rapid, inexpensive and benchtop-based integrated fabrication process presented here, we expect this method to be applicable to the rapid prototyping and fabrication of several fully-integrated biosensing systems for POC diagnostic applications.
