TIAN Lab developed several types of MEMS chips to meet the urgent need of low-cost sensitive accurate biosensors for early diagnosis of cancers in low-income countries. He addressed two major bottlenecks of biosensors including low sensitivity and narrow sensing range. He invented the shrink polymer nanolithography and developed a suspended graphene sensor array with nanoscale linewidth to solve the problem of interface scattering during electron transport, significantly improving detection resolution. He developed a nano-wrinkled sensor, addressing the challenge of limited contact area and narrow detection range of planar electrodes. Even compared to the world’s most advanced Siemens ADVIA analyzer, the resolution of these sensors has improved by 250 times of magnitude (from 0.1e-12 g/mL to 0.4e-15 g/mL), and the detection range has expanded by two orders of magnitude (from 1e-12 g/mL to 1e-5 g/mL, extending to 1e-14 g/mL to 1e-5 g/mL). Collaborating with Mayo Clinic and Cleveland Clinic, MEMS chips can achieve an early screening accuracy rate of 98.3% with 20% of the conventional diagnosis cost, which is significant improvement over larger instruments like the Siemens ADVIA analyzer.
TIAN Lab developed polymer microelectronics for bio-sensing and its integration for MEMS. This lab was the first one to combine micro and nano fabrication technologies to realize polymer- and nanoparticle-based electronics devices for low-cost, flexible, and disposable immunosensors. The single-walled carbon nanotubes (SWNT) and biomolecules are self-assembled on micro patterned electrodes. The immuno-chip acts as the platform of a horseradish peroxidase (HRP) labeled sandwiched Enzyme-Linked ImmunoSorbent Assay (ELISA). The pH change induced by the biochemical reactions influences the electrical conductance of SWNT. The detection resolution of 0.4 ng/ml (2.5 pM) for normal rabbit immunoglobulin G (IgG) is demonstrated. The new fabrication technique and the HRP labeled detection protocol can be extended to the recognition of other viruses or bacteria for critical applications to clinical diagnosis, food toxin detection, environment monitoring, etc.
TIAN Lab developed a new hot embossing process to develop an innovative polymer array with 384 wells and polymer dispensing well plates to address the urgent need of low-cost devices and consumables for high-throughput automatic polymerase chain reaction (PCR) of DNA. This technology provides key devices for high-throughput PCR at low cost to a variety of end-users, including agriculture biology and clinical research laboratories. Polymer hot embossing is a very versatile replication method which uses high pressure and elevated temperatures to transfer structures from a master into a polymer. It addresses a wide range of applications, from polymer-based lab-on-chip systems, where imprinting is done on thick polymers substrates to the fabrication of nanometer scale features for nano-electronics, bio-sensing or data recording applications, where imprinting is required. Polymers offer many advantages for micro and nano devices, including low material cost for high-volume fabrication, inexpensive fabrication methods, wide range of material properties and surface chemistries available, chemical and biological compatibility, ease of manufacturing due to replication methods, and suitable microfabrication technologies for a large variety of geometries. In Tian Lab, researchers made high-precision nickel molds with three-level electroplating and successfully developed hot-embossing process for mass fabrication of polymer arrays with 384 well and polymer dispensing well plates.
TIAN Lab investigates single-stranded DNA sensing by introducing a novel approach integrating laser-induced graphene (LIG) heaters and CRISPR-Cas9 sensors for efficient DNA amplification and detection. The LIG heater, fabricated through laser-induced carbonization of polyimide tape, enables rapid and precise temperature control with minimal power consumption, supporting isothermal Loop-Mediated Amplification (LAMP) for less than 30 minutes. Simultaneously, the CRISPR-Cas9 biosensor provides highly specific DNA detection down to 16 pM amplified from single-stranded DNA, leveraging the electrochemical properties of pyrolytic glassy carbon electrodes. This combined system demonstrates significant improvements in power efficiency, cost-effectiveness, and simplicity compared to traditional methods, making it particularly suited for portable molecular diagnostics. By validating the system through lateral flow assays and showcasing its potential for precise, low-cost DNA analysis, the study paves the way for innovative applications to nucleic acid diagnostics and resource-efficient pathogen detection.
TIAN Lab makes significant advancements in developing ultra-sensitive and highly selective electrochemical sensors for neurotransmitter detection. These innovations leverage cutting-edge materials and fabrication techniques to address critical challenges, including biofouling, interference from coexisting molecules, and low detection limits. One highlight is the development of antifouling sensors based on shrink polymers, incorporating nano-wrinkles and electrostatic repulsion modifications. These sensors effectively limit protein adsorption, maintaining over 93% signal integrity in complex biofluids such as serum and whole blood while ensuring long-term stability. This technology demonstrates excellent performance in dopamine detection with a wide dynamic range and low detection limits. Additionally, we developed flexible sensors combining graphene and gold nanoparticles, significantly enhancing sensitivity and selectivity. The heterostructure electrodes exhibit superior mass transfer properties and effectively distinguish the electrochemical peaks of dopamine and uric acid. By employing multilayer graphene and gold nanoparticle assemblies, these sensors achieve a detection limit of dopamine as low as 10 nM. Furthermore, we explored flexible substrates and microelectrode fabrication techniques to improve sensor compatibility with biological tissues. For instance, polyolefin-based flexible substrates integrated with self-assembled graphene layers significantly reduce interference from ascorbic acid, a common confounder in dopamine detection. This approach not only enhances selectivity but also ensures mechanical stability and flexibility, making these sensors suitable for integration with flexible neural interfaces. Overall, these advancements lay a solid foundation for developing next-generation electrochemical sensors capable of real-time neurotransmitter monitoring in complex environments. By integrating advanced materials such as shrink polymers, graphene composites, and gold nanoparticle-modified electrodes into sensor design, our team is addressing critical challenges in neurochemical sensing with high precision and reliability, paving the way for future technological breakthroughs.
TIAN Lab introduces a novel particle focusing technique for Impedance Flow Cytometry (IFC) utilizing acoustic excitation in a microchannel with air pockets. By applying specific excitation frequencies, the oscillating air-water interfaces generate secondary flows that direct particles into focused trajectories, enhancing the precision of downstream impedance measurements. Experimental results demonstrate two distinct particle focusing modes based on the excitation frequency. At higher frequencies, particles are directed toward the channel center, while at lower frequencies, a single vortex pattern is formed, pushing larger particles away from the interface. This technique significantly improves the stability and accuracy of impedance measurements, reducing the standard deviation of peak heights from 0.0096 mV to 0.0021 mV, thus proving its potential for diverse biomedical applications. This innovative method offers a user-friendly and highly adaptable approach to addressing challenges in IFC, such as position variability and measurement inconsistencies caused by non-uniform electric fields. Unlike traditional methods requiring precise microfluidic control or additional equipment like sheath fluids, this technique simplifies the system while enhancing its usability and reliability. The findings lay the groundwork for more efficient and accessible IFC systems, promoting advancements in biomedical diagnostics, cellular analysis, and particle manipulation in microfluidics.