Ph.D., University of Arizona, Mechanical Engineering (2011)
M.Phil., Chinese University of Hong Kong, Physics (2002)
B.S., University of Hong Kong, Physics (2000)
Joseph Liao, Postdoctoral Faculty Sponsor
Current Research and Scholarly Interests
Advances and challenges in biosensor-based diagnosis of infectious diseases
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
2014; 14 (2): 225-244
Rapid diagnosis of infectious diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in biosensor technologies have potential to deliver point-of-care diagnostics that match or surpass conventional standards in regards to time, accuracy and cost. Broadly classified as either label-free or labeled, modern biosensors exploit micro- and nanofabrication technologies and diverse sensing strategies including optical, electrical and mechanical transducers. Despite clinical need, translation of biosensors from research laboratories to clinical applications has remained limited to a few notable examples, such as the glucose sensor. Challenges to be overcome include sample preparation, matrix effects and system integration. We review the advances of biosensors for infectious disease diagnostics and discuss the critical challenges that need to be overcome in order to implement integrated diagnostic biosensors in real world settings.
View details for DOI 10.1586/14737159.2014.888313
View details for Web of Science ID 000335324700011
View details for PubMedID 24524681
Electrokinetic stringency control in self-assembled monolayer-based biosensors for multiplex urinary tract infection diagnosis
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
2014; 10 (1): 159-166
Rapid detection of bacterial pathogens is critical toward judicious management of infectious diseases. Herein, we demonstrate an in situ electrokinetic stringency control approach for a self-assembled monolayer-based electrochemical biosensor toward urinary tract infection diagnosis. The in situ electrokinetic stringency control technique generates Joule heating induced temperature rise and electrothermal fluid motion directly on the sensor to improve its performance for detecting bacterial 16S rRNA, a phylogenetic biomarker. The dependence of the hybridization efficiency reveals that in situ electrokinetic stringency control is capable of discriminating single-base mismatches. With electrokinetic stringency control, the background noise due to the matrix effects of clinical urine samples can be reduced by 60%. The applicability of the system is demonstrated by multiplex detection of three uropathogenic clinical isolates with similar 16S rRNA sequences. The results demonstrate that electrokinetic stringency control can significantly improve the signal-to-noise ratio of the biosensor for multiplex urinary tract infection diagnosis.Urinary tract infections remain a significant cause of mortality and morbidity as secondary conditions often related to chronic diseases or to immunosuppression. Rapid and sensitive identification of the causative organisms is critical in the appropriate management of this condition. These investigators demonstrate an in situ electrokinetic stringency control approach for a self-assembled monolayer-based electrochemical biosensor toward urinary tract infection diagnosis, establishing that such an approach significantly improves the biosensor's signal-to-noise ratio.
View details for DOI 10.1016/j.nano.2013.07.006
View details for Web of Science ID 000329103500017
View details for PubMedID 23891989
- A Universal Electrode Approach for Automated Electrochemical Molecular Analyses JOURNAL OF MICROELECTROMECHANICAL SYSTEMS 2013; 22 (5): 1126-1132
An AC electrokinetics facilitated biosensor cassette for rapid pathogen identification
2013; 138 (13): 3660-3666
To develop a portable point-of-care system based on biosensors for common infectious diseases such as urinary tract infection, the sensing process needs to be implemented within an enclosed fluidic system. On chip sample preparation of clinical samples remains a significant obstacle to achieving robust sensor performance. Herein AC electrokinetics is applied in an electrochemical biosensor cassette to enhance molecular convection and hybridization efficiency through electrokinetics induced fluid motion and Joule heating induced temperature elevation. Using E. coli as an exemplary pathogen, we determined the optimal electrokinetic parameters for detecting bacterial 16S rRNA in the biosensor cassette based on the current output, signal-to-noise ratio, and limit of detection. In addition, a panel of six probe sets targeting common uropathogenic bacteria was demonstrated. The optimized parameters were also validated using patient-derived clinical urine samples. The effectiveness of electrokinetics for on chip sample preparation will facilitate the implementation of point-of-care diagnosis of urinary tract infection in the future.
View details for DOI 10.1039/c3an00259d
View details for Web of Science ID 000319876800012
View details for PubMedID 23626988
In Situ Electrokinetic Enhancement for Self-Assembled-Monolayer-Based Electrochemical Biosensing
2012; 84 (6): 2702-2707
This study reports a multifunctional electrode approach which directly implements electrokinetic enhancement on a self-assembled-monolayer-based electrochemical sensor for point-of-care diagnostics. Using urinary tract infections as a model system, we demonstrate that electrokinetic enhancement, which involves in situ stirring and heating, can enhance the sensitivity of the strain specific 16S rRNA hybridization assay for 1 order of magnitude and accelerate the time-limiting incubation step with a 6-fold reduction in the incubation time. Since the same electrode platform is used for both electrochemical signal enhancement and electrochemical sensing, the multifunctional electrode approach provides a highly effective strategy toward fully integrated lab-on-a-chip systems for various biomedical applications.
View details for DOI 10.1021/ac203245j
View details for Web of Science ID 000301634500013
View details for PubMedID 22397486
Electrokinetic focusing and separation of mammalian cells in conductive biological fluids
2012; 137 (22): 5215-5221
Active manipulation of cells, such as trapping, focusing, and isolation, is essential for various bioanalytical applications. Herein, we report a hybrid electrokinetic technique for manipulating mammalian cells in physiological fluids. This technique applies a combination of negative dielectrophoretic force and hydrodynamic drag force induced by electrohydrodynamics, which is effective in conductive biological fluids. With a three-electrode configuration, the stable equilibrium positions of cells can be adjusted for separation and focusing applications. Cancer cells and white blood cells can be positioned and isolated into specific locations in the microchannel under both static and dynamic flow conditions. To investigate the sensitivity of the hybrid electrokinetic process, AC voltage, frequency, and bias dependences of the cell velocity were studied systematically. The applicability of the hybrid electrokinetic technique for manipulating cells in physiological samples is demonstrated by continuous focusing of human breast adenocarcinoma spiked in urine, buffy coats, and processed blood samples with 98% capture efficiency.
View details for DOI 10.1039/c2an35707k
View details for Web of Science ID 000309839400008
View details for PubMedID 22937529
- Microfluidic-based biosensors toward point-of-care detection of nucleic acids and proteins MICROFLUIDICS AND NANOFLUIDICS 2011; 10 (2): 231-247
Hybrid electrokinetic manipulation in high-conductivity media
LAB ON A CHIP
2011; 11 (10): 1770-1775
This study reports a hybrid electrokinetic technique for label-free manipulation of pathogenic bacteria in biological samples toward medical diagnostic applications. While most electrokinetic techniques only function in low-conductivity buffers, hybrid electrokinetics enables effective operation in high-conductivity samples, such as physiological fluids (?1 S m(-1)). The hybrid electrokinetic technique combines short-range electrophoresis and dielectrophoresis, and long-range AC electrothermal flow to improve its effectiveness. The major technical hurdle of electrode instability for manipulating high conductivity samples is tackled by using a Ti-Au-Ti sandwich electrode and a 3-parallel-electrode configuration is designed for continuous isolation of bacteria. The device operates directly with biological samples including urine and buffy coats. We show that pathogenic bacteria and biowarfare agents can be concentrated for over 3 orders of magnitude using hybrid electrokinetics.
View details for DOI 10.1039/c1lc20054b
View details for Web of Science ID 000289951200009
View details for PubMedID 21487576
System Integration - A Major Step toward Lab on a Chip.
Journal of biological engineering
2011; 5: 6-?
Microfluidics holds great promise to revolutionize various areas of biological engineering, such as single cell analysis, environmental monitoring, regenerative medicine, and point-of-care diagnostics. Despite the fact that intensive efforts have been devoted into the field in the past decades, microfluidics has not yet been adopted widely. It is increasingly realized that an effective system integration strategy that is low cost and broadly applicable to various biological engineering situations is required to fully realize the potential of microfluidics. In this article, we review several promising system integration approaches for microfluidics and discuss their advantages, limitations, and applications. Future advancements of these microfluidic strategies will lead toward translational lab-on-a-chip systems for a wide spectrum of biological engineering applications.
View details for DOI 10.1186/1754-1611-5-6
View details for PubMedID 21612614
Electrothermal Fluid Manipulation of High-Conductivity Samples for Laboratory Automation Applications
2010; 15 (6): 426-432
Electrothermal flow is a promising technique in microfluidic manipulation toward laboratory automation applications, such as clinical diagnostics and high throughput drug screening. Despite the potential of electrothermal flow in biomedical applications, relative little is known about electrothermal manipulation of highly conductive samples, such as physiological fluids and buffer solutions. In this study, the characteristics and challenges of electrothermal manipulation of fluid samples with different conductivities were investigated systematically. Electrothermal flow was shown to create fluid motion for samples with a wide range of conductivity when the driving frequency was above 100 kHz. For samples with low conductivities (below 1 S/m), the characteristics of the electrothermal fluid motions were in quantitative agreement with the theory. For samples with high conductivities (above 1 S/m), the fluid motion appeared to deviate from the model as a result of potential electrochemical reactions and other electrothermal effects. These effects should be taken into consideration for electrothermal manipulation of biological samples with high conductivities. This study will provide insights in designing microfluidic devices for electrokinetic manipulation of biological samples toward laboratory automation applications in the future.
View details for DOI 10.1016/j.jala.2010.05.004
View details for Web of Science ID 000285116600003
View details for PubMedID 21180401
Electrochemical immunosensor detection of urinary lactoferrin in clinical samples for urinary tract infection diagnosis
BIOSENSORS & BIOELECTRONICS
2010; 26 (2): 649-654
Urine is the most abundant and easily accessible of all body fluids and provides an ideal route for non-invasive diagnosis of human diseases, particularly of the urinary tract. Electrochemical biosensors are well suited for urinary diagnostics due to their excellent sensitivity, low-cost, and ability to detect a wide variety of target molecules including nucleic acids and protein biomarkers. We report the development of an electrochemical immunosensor for direct detection of the urinary tract infection (UTI) biomarker lactoferrin from infected clinical samples. An electrochemical biosensor array with alkanethiolate self-assembled monolayer (SAM) was used. Electrochemical impedance spectroscopy was used to characterize the mixed SAM, consisted of 11-mercaptoundecanoic acid and 6-mercapto-1-hexanol. A sandwich amperometric immunoassay was developed for detection of lactoferrin from urine, with a detection limit of 145 pg/ml. We validated lactoferrin as a biomarker of pyuria (presence of white blood cells in urine), an important hallmark of UTI, in 111 patient-derived urine samples. Finally, we demonstrated multiplex detection of urinary pathogens and lactoferrin through simultaneous detection of bacterial nucleic acid (16S rRNA) and host immune response protein (lactoferrin) on a single sensor array. Our results represent first integrated sensor platform capable of quantitative pathogen identification and measurement of host immune response, potentially providing clinical diagnosis that is not only more expeditious but also more informative than the current standard.
View details for DOI 10.1016/j.bios.2010.07.002
View details for Web of Science ID 000283804400056
View details for PubMedID 20667707
Antimicrobial Susceptibility Testing Using High Surface-to-Volume Ratio Microchannels
2010; 82 (3): 1012-1019
This study reports the use of microfluidics, which intrinsically has a large surface-to-volume ratio, toward rapid antimicrobial susceptibility testing at the point of care. By observing the growth of uropathogenic Escherichia coli in gas permeable polymeric microchannels with different dimensions, we demonstrate that the large surface-to-volume ratio of microfluidic systems facilitates rapid growth of bacteria. For microchannels with 250 microm or less in depth, the effective oxygenation can sustain the growth of E. coli to over 10(9) cfu/mL without external agitation or oxygenation, which eliminates the requirement of bulky instrumentation and facilitates rapid bacterial growth for antimicrobial susceptibility testing at the point of care. The applicability of microfluidic rapid antimicrobial susceptibility testing is demonstrated in culture media and in urine with clinical bacterial isolates that have different antimicrobial resistance profiles. The antimicrobial resistance pattern can be determined as rapidly as 2 h compared to days in standard clinical procedures facilitating diagnostics at the point of care.
View details for DOI 10.1021/ac9022764
View details for Web of Science ID 000273983700037
View details for PubMedID 20055494
Hybrid electrokinetics for separation, mixing, and concentration of colloidal particles
2009; 20 (16)
The advent of nanotechnology has facilitated the preparation of colloidal particles with adjustable sizes and the control of their size-dependent properties. Physical manipulation, such as separation, mixing, and concentration, of these colloidal particles represents an essential step for fully utilizing their potential in a wide spectrum of nanotechnology applications. In this study, we investigate hybrid electrokinetics, the combination of dielectrophoresis and electrohydrodynamics, for active manipulation of colloidal particles ranging from nanometers to micrometers in size. A concentric electrode configuration, which is optimized for generating electrohydrodynamic flow, has been designed to elucidate the effectiveness of hybrid electrokinetics and define the operating regimes for different microfluidic operations. The results indicate that the relative importance of electrohydrodynamics increases with decreasing particle size as predicted by a scaling analysis and that electrohydrodynamics is pivotal for manipulating nanoscale particles. Using the concentric electrodes, we demonstrate separation, mixing, and concentration of colloidal particles by adjusting the relative strengths of different electrokinetic phenomena. The effectiveness of hybrid electrokinetics indicates its potential to serve as a generic technique for active manipulation of colloidal particles in various nanotechnology applications.
View details for DOI 10.1088/0957-4484/20/16/165701
View details for Web of Science ID 000264780200014
View details for PubMedID 19420574
- Active manipulation of quantum dots using AC electrokinetics J Phys Chem C 2009; 113 (16): 6561-6565
- Ultralow-power alcohol vapor sensors using chemically functionalized multiwalled carbon nanotubes IEEE TRANSACTIONS ON NANOTECHNOLOGY 2007; 6 (5): 571-577
- Molecular interfacial engineering of adhesion between polyfluorene and indium-tin oxide APPLIED PHYSICS A-MATERIALS SCIENCE & PROCESSING 2007; 87 (1): 23-26
- Development of an automated microspotting system for rapid dielectrophoretic fabrication of bundled carbon nanotube sensors IEEE TRANSACTIONS ON AUTOMATION SCIENCE AND ENGINEERING 2006; 3 (3): 218-227
- Structural transformation of mixed C-60 and C-70 fullerene monolayer on Ag(100) JAPANESE JOURNAL OF APPLIED PHYSICS PART 1-REGULAR PAPERS BRIEF COMMUNICATIONS & REVIEW PAPERS 2006; 45 (3B): 2377-2381
- Characterization and control of molecular ordering on adsorbate-induced reconstructed surfaces APPLIED SURFACE SCIENCE 2005; 241 (1-2): 194-198