Precise detection of trace amount of molecules, such as the disease biomarkers present in biofluids or explosive residues, requires high sensitivity detection. electrospray ionization–mass spectrometry (ESI-MS) is a common and effective technique for sensitive trace molecular detection in small-volume liquid samples. In ESI-MS, nano-liter volume samples are ionized and aerosolized by ESI, and fed into MS for mass analysis. ESI-MS has proven to be a reliable ionization technique for coupling liquid phase separations like liquid chromatography (LC) and capillary zone electrophoresis (CE) with the highly specific resolving power of MS. While CE and ESI can be performed on a microfluidic chip having a footprint of a few cm2, MS is typically at least 100 times bigger in size than a micro-chip. A reduced size, weight, and power profile would enable semi-portable applications in forensics, environmental monitoring, defense, and biological/pharmaceutical applications. To achieve this goal, we present an initial study evaluating the use of mid-infrared absorption spectroscopy (MIRAS) in place of MS to create a ESI-MIRAS system. To establish feasibility, we perform ESI-MIRAS on phospholipid samples, which have been previously demonstrated to be separable by CE. Phospholipids are biomarkers of degenerative neurological, kidney, and bone diseases and can be found in biofluids such as blood, urine and cerebrospinal fluid. To establish sensitivity limits, calibration samples of 100 μM concentration are electrospray deposited on to a grounded Si wafer for different times (1 minutes to 4 minutes with a 1 minute step). The minimum detectable concentration-time product, where a FTIR globar is used as the MIR source, is found ~200 μM·s.
Multiphoton microscopy (MPM) imaging of intrinsic two-photon excited fluorescence (TPEF) is performed on humanized sickle cell disease (SCD) mouse model splenic tissue. Distinct morphological and spectral features associated with SCD are identified and discussed in terms of diagnostic relevance. Specifically, spectrally unique splenic iron-complex deposits are identified by MPM; this finding is supported by TPEF spectroscopy and object size to standard histopathological methods. Further, iron deposits are found at higher concentrations in diseased tissue than in healthy tissue by all imaging methods employed here including MPM, and therefore, may provide a useful biomarker related to the disease state. These newly characterized biomarkers allow for further investigations of SCD in live animals as a means to gain insight into the mechanisms impacting immune dysregulation and organ malfunction, which are currently not well understood.
We present our study on compact, label-free dissolved lipid sensing by combining capillary electrophoresis
separation in a PDMS microfluidic chip online with mid-infrared (MIR) absorption spectroscopy for biomarker
detection. On-chip capillary electrophoresis is used to separate the biomarkers without introducing any extrinsic
contrast agent, which reduces both cost and complexity. The label free biomarker detection could be done by
interrogating separated biomarkers in the channel by MIR absorption spectroscopy. Phospholipids biomarkers of
degenerative neurological, kidney, and bone diseases are detectable using this label free technique. These
phospholipids exhibit strong absorption resonances in the MIR and are present in biofluids including urine, blood
plasma, and cerebrospinal fluid. MIR spectroscopy of a 12-carbon chain phosphatidic acid (PA) (1,2-dilauroyl-snglycero-
3-phosphate (sodium salt)) dissolved in N-methylformamide, exhibits a strong amide peak near
wavenumber 1660 cm-1 (wavelength 6 μm), arising from the phosphate headgroup vibrations within a low-loss
window of the solvent. PA has a similar structure to many important phospholipids molecules like
phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatidylglycerol (PG),
and phosphatidylserine (PS), making it an ideal molecule for initial proof-of-concept studies. This newly proposed
detection technique can lead us to minimal sample preparation and is capable of identifying several biomarkers from
the same sample simultaneously.
We present Finite-Difference Time-Domain (FDTD) simulations to explore feasibility of chip-to-chip waveguide
coupling via Optical Quilt Packaging (OQP). OQP is a newly proposed scheme for wide-bandwidth, highly-efficient
waveguide coupling and is suitable for direct optical interconnect between semiconductor optical sources, optical
waveguides, and detectors via waveguides. This approach leverages advances in quilt packaging (QP), an electronic
packaging technique wherein contacts formed along the vertical faces are joined to form electrically-conductive and
mechanically-stable chip-to-chip contacts. In OQP, waveguides of separate substrates are aligned with sub-micron
accuracy by protruding lithographically-defined copper nodules on the side of a chip. With OQP, high efficiency chip-to-chip
optical coupling can be achieved by aligning waveguides of separate chips with sub-micron accuracy and reducing
chip-to-chip distance. We used MEEP (MIT Electromagnetic Equation Propagation) to investigate the feasibility of OQP
by calculating the optical coupling loss between butt coupled waveguides. Transmission between a typical QCL ridge
waveguide and a single-mode Ge-on-Si waveguide was calculated to exceed 65% when an interchip gap of 0.5 μm and
to be no worse than 20% for a gap of less than 4 μm. These results compare favorably to conventional off-chip coupling.
To further increase the coupling efficiency and reduce sensitivity to alignment, we used a horn-shaped Ge-on-Si
waveguide and found a 13% increase in coupling efficiency when the horn is 1.5 times wider than the wavelength and 2
times longer than the wavelength. Also when the horizontal misalignment increases, coupling loss of the horn-shaped
waveguide increases at a slower rate than a ridge waveguide.