Saara A. Khan

Label-free and non-contact optical biosensing of glucose with quantum dots

We present a label-free, optical sensor for biomedical applications based on changes in the visible photoluminescence (PL) of quantum dots in a thin polymer film. Using glucose as the target molecule, the screening of UV excitation due to pre-absorption by the product of an enzymatic assay leads to quenching of the PL of quantum dots (QDs) in a non-contact scheme. The irradiance changes in QD PL indicate quantitatively the level of glucose present. The non-contact nature of the assay prevents surface degradation of the QDs, which yields an efficient, waste-free, cost-effective, portable, and sustainable biosensor with attractive market features. The limit of detection of the demonstrated biosensor is ~3.5 µm, which is competitive with existing contact-based bioassays. In addition, the biosensor operates over the entire clinically relevant range of glucose concentrations of biological fluids including urine and whole blood. The comparable results achieved across a range of cost-affordable detectors, including a spectrophotometer, portable spectrometer, and iPhone camera, suggest that label-free and visible quantification of glucose with QD films can be applied to low-cost, point-of-care biomedical sensing as well as scientific applications in the laboratory for characterizing glucose or other analytes.

Three-dimensional, distendable bladder phantom for optical coherence tomography and white light cystoscopy

Abstract. We describe a combination of fabrication techniques and a general process to construct a three-dimensional (3-D) phantom that mimics the size, macroscale structure, microscale surface topology, subsurface microstructure, optical properties, and functional characteristics of a cancerous bladder. The phantom also includes features that are recognizable in white light (i.e., the visual appearance of blood vessels), making it suitable to emulate the bladder for emerging white light+optical coherence tomography (OCT) cystoscopies and other endoscopic procedures of large, irregularly shaped organs. The fabrication process has broad applicability and can be generalized to OCT phantoms for other tissue types or phantoms for other imaging modalities. To this end, we also enumerate the nuances of applying known fabrication techniques (e.g., spin coating) to contexts (e.g., nonplanar, 3-D shapes) that are essential to establish their generalizability and limitations. We anticipate that this phantom will be immediately useful to evaluate innovative OCT systems and software being developed for longitudinal bladder surveillance and early cancer detection.

Scalable multiplexing for parallel imaging with interleaved optical coherence tomography

We demonstrate highly parallel imaging with interleaved optical coherence tomography (iOCT) using an in-house-fabricated, air-spaced virtually-imaged phased array (VIPA). The air-spaced VIPA performs spectral encoding of the interferograms from multiple lateral points within a single sweep of the source and allows us to tune and balance several imaging parameters: number of multiplexed points, ranging depth, and sensitivity. In addition to a thorough discussion of the parameters and operating principles of the VIPA, we experimentally demonstrate the effect of different VIPA designs on the multiplexing potential of iOCT. Using a 200-kHz light source, we achieve an effective A-scan rate of 3.2-MHz by multiplexing 16 lateral points onto a single wavelength sweep. The improved sensitivity of this system is demonstrated for 3D imaging of biological samples such as a human finger and a fruit fly.

Optical separation of heterogeneous size distributions of microparticles on silicon nitride strip waveguides

We demonstrate two complementary optical separation techniques of dielectric particles on the surface of silicon nitride waveguides. Glass particles ranging from 2 μm to 10 μm in diameter are separated at guided powers below 40 mW. The effects of optical, viscous, and frictional forces on the particles are modeled and experimentally shown to enable separation. Particle interactions are investigated and shown to decrease measured particle velocity without interfering with the overall particle separation distribution. The demonstrated separation techniques have the potential to be integrated with microfluidic structures for cell sorting.

Multilayered disease-mimicking bladder phantom with realistic surface topology for optical coherence tomography

Optical coherence tomography (OCT) has shown potential as a complementary modality to white light cystoscopy (WLC), the gold standard for imaging bladder cancer. OCT can visualize sub-surface details of the bladder wall, which enables it to stage cancers and detect tumors that are otherwise invisible to WLC. Currently, OCT systems have too slow a speed and too small a field of view for comprehensive bladder imaging, which limits its clinical utility. Validation and feasibility testing of technological refinements aimed to provide faster imaging and wider fields of view necessitates a realistic bladder phantom. We present a novel process to fabricate the first such phantom that mimics both the optical and morphological properties of layers of the healthy and pathologic bladder wall as they characteristically appear with OCT. The healthy regions of the silicone-based phantom comprises three layers: the urothelium, lamina propria and muscularis propria, each containing an appropriate concentration of titanium dioxide to mimic its distinct scattering properties. As well, the layers each possess a unique surface appearance imposed by a textured mold. Within this phantom, pathologic tissue-mimicking regions are created by thickening specific layers or creating inclusions that disrupt the layered appearance of the bladder wall, as is characteristic of bladder carcinomas. This phantom can help to evaluate the efficacy of new OCT systems and software for tumor localization. Moreover, the procedure we have developed is highly generalizable for the creation of OCT-relevant, multi-layer phantoms for tissues that incorporate diseased states characterized by the loss of layered structures.

Waveguide optical tweezers for selective cell lysis

Waveguide evanescent fields enable lysing of selected red blood cells. Cells are trapped on waveguides and are lysed by rapidly reducing the trapping forces. Red blood cells of different age require different levels of lysing power, allowing selective lysing of crenate cells.

Reducing user error in dipstick urinalysis with a low-cost slipping manifold and mobile phone platform (Conference Presentation)

Urinalysis dipsticks were designed to revolutionize urine-based medical diagnosis. They are cheap, extremely portable, and have multiple assays patterned on a single platform. They were also meant to be incredibly easy to use. Unfortunately, there are many aspects in both the preparation and the analysis of the dipsticks that are plagued by user error. This high error is one reason that dipsticks have failed to flourish in both the at-home market and in low-resource settings. Sources of error include: inaccurate volume deposition, varying lighting conditions, inconsistent timing measurements, and misinterpreted color comparisons. We introduce a novel manifold and companion software for dipstick urinalysis that eliminates the aforementioned error sources. A micro-volume slipping manifold ensures precise sample delivery, an opaque acrylic box guarantees consistent lighting conditions, a simple sticker-based timing mechanism maintains accurate timing, and custom software that processes video data captured by a mobile phone ensures proper color comparisons. We show that the results obtained with the proposed device are as accurate and consistent as a properly executed dip-and-wipe method, the industry gold-standard, suggesting the potential for this strategy to enable confident urinalysis testing. Furthermore, the proposed all-acrylic slipping manifold is reusable and low in cost, making it a potential solution for at-home users and low-resource settings.

Colloidal Quantum Dots for Cost-effective, Miniaturized, and Simple Spectrometers

According to a market report published by Transparency Market Research (1), the global spectrometry market was valued at

Optical propulsion and sorting of microparticles on silicon nitride strip waveguides

12.2 billion in 2013 and is estimated to reach

Label-free assay for the detection of glucose mediated by the effects of narrowband absorption on quantum dot photoluminescence

19.6 billion by 2020. The market can be divided into 3 categories: atomic spectrometry, mass spectrometry, and molecular spectrometry. As of 2013, molecular spectrometry reportedly had the highest market share of the 3 spectrometry techniques. Not surprisingly, there has been a large surge in interest for handheld and portable molecular spectrometers for consumers, food suppliers, pharmaceutical companies, and the military, with a vast range of applications. Handheld and miniaturized molecular spectrometers have primarily delivered capabilities for color measurement or spectrometry in the ultraviolet-visible (UV-VIS),3 near infrared, or infrared (IR) ranges, but several factors can limit their performance. In particular, the resolution and spectral range of the spectrometer are highly dependent on the inherent design. To date, most spectrometers use interference filters and interferometric optics as the basis of operation. However, a recent paper in Nature Letters describes a miniaturized spectrometer that uses the absorption spectrum of colloidal quantum dots (CQDs) overlaid on a charge-coupled device (CCD) detector as an alternative to interferometric techniques (2). The CQD spectrometer exploits the absorption spectrum of 195 different types of quantum dots to cover a spectral range of 300 nm (390–690 nm). The performance of the CQD spectrometer was demonstrated through its ability to measure shifts in spectral peaks as small as 1 nm. The spectral resolving capability between 2 peaks in the ideal case (no measurement or instrument noise present in system) is 3.2 nm. The CQD materials comprised aliquots of CdS and CdSe preparations, which were converted into broadband wavelength filters by quenching the fluorescent emission of the CQDs through …