In recent years, Surface Enhanced Raman Scattering (SERS) has been widely applied to many different areas, including chemical analysis, biomolecule detection, bioagent diagnostics, DNA sequence, and environmental monitor, due to its capabilities of unlabeled fingerprint identification, high sensitivity, and rapid detection. In biomicrofluidic systems, it is also very powerful to integrate SERS based devices with specified micro-fluid flow fields to further focusing/enhancing/multiplexing SERS signals through molecule registration, concentration/accumulation, and allocation. In this review, after a brief introduction of the mechanism of SERS detection on proteins, we will first focus on the effectiveness of different nanostructures for SERS enhancement and light-to-heat conversion in trace protein analysis. Various protein molecule accumulation schemes by either (bio-)chemical or physical ways, such as immuno, electrochemical, Tip-enhanced Raman spectroscopy, and magnetic, will then be reviewed for further SERS signal amplification. The analytical and repeatability/stability issues of SERS detection on proteins will also be brought up for possible solutions. Then, the comparison about various ways employing microfluidic systems to register, concentrate, and enhance the signals of SERS and reduce the background noise by active or passive means to manipulate SERS nanostructures and protein molecules will be elaborated. Finally, we will carry on the discussion on the challenges and opportunities by introducing SERS into biomicrofluidic systems and their potential solutions.
A microfluidic chip, which can separate and enrich leukocytes from whole blood, is proposed. The chip has 10 switchback curve channels, which are connected by straight channels. The straight channels are designed to permit the inertial migration effect and to concentrate the blood cells, while the curve channels allow the Dean flow to further classify the blood cells based on the cell sizes. Hydrodynamic suction is also utilized to remove smaller blood cells (e.g., red blood cell (RBC)) in the curve channels for higher separation purity. By employing the inertial migration, Dean flow force, and hydrodynamic suction in a continuous flow system, our chip successfully separates large white blood cells (WBCs) from the whole blood with the processing rates as high as 1 × 108 cells/sec at a high recovery rate at 93.2% and very few RBCs (~0.1%).
Circulation tumor cells (CTCs) play an important role in metastasis and highly correlate with cancer progression; thus, CTCs could be considered as a powerful diagnosis tool. Our previous studies showed that the number of CTCs could be utilized for recurrence prediction in colorectal cancer (CRC); however, the odds ratio was still lower than five. To improve prognosis in CRC patients, we analyzed CTC clusters/microemboli, CTC numbers, and carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9) levels using a self-assembled cell array (SACA) chip system for recurrence prediction. In CRC patients, the presence of CTC clusters/microemboli may have higher correlation in metastasis when compared to the high number of CTCs. Additionally, when both the number of CTCs and serum CEA levels are high, very high odds ratios of 24.4 and 17.1 are observed in patients at all stages and stage III of CRC, respectively. The high number of CTCs and CTC clusters/microemboli simultaneously suggests the high chance of relapse (odds ratio 8.4). Overall, the characteristic of CTC clusters/microemboli, CEA level, and CTC number have a clinical potential to enhance CRC prognosis.
Electrodynamic systems
for bioanalytical applications constantly
suffer from biofouling due to electrical field-induced nonspecific
bioadsorption on electrode surfaces. To minimize this issue, surface
modification using anti-biofouling and conductive materials is necessary
to not only protect the electrode surface from nonspecific bioadsorption
but also maintain desired electrodynamic properties for electrode
operation. In this study, we designed and prepared a conductive, zwitterionic,
and self-doped sulfonated polyaniline (SPANI) coating on Au electrode
surfaces for anti-biofouling applications. The zwitterionic coating
was fabricated by electrochemical polymerization of aniline on the
Au electrode surface functionalized with cysteamine (HS−CH2CH2−NH2) and then a post-polymerization
treatment with fuming sulfuric acid. We found that the SPANI-coated
electrodes exhibited an excellent anti-biofouling ability in dielectrophoresis
(DEP) capturing-and-releasing processes, with a very low average residual
mass rate of 1.44% for the SPANI-5s electrode, whereas electrodes
modified with poly(ethylene glycol) (PEG) gave an average residual
mass rate of 14.30%. Even under continuous operation for more than
1 h, the SPANI-5s electrode still showed stable anti-biofouling ability
for an 11-cycle E. coli capturing-and-releasing DEP
process, with the residual mass rate for all 11 cycles being kept
at or below 2.18% to give an average residual mass rate of 1.62% with
a standard deviation of 0.40%. This study demonstrates that electrodynamic
systems with zwitterionic SPANI coated on open electrode surfaces
can excellently function with decent conductance and anti-biofouling
performance.
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