None.

All the protocols described below follow the guidelines of the Human Research Ethics Committee of the First Affiliated Hospital of Harbin Medical University and adhere to the tenets of the Declaration of Helsinki. The approval number is 2023IIT008. Written, informed consent was obtained from all study participants. The study included participants who presented with conjunctival masses. Exclusion criteria for enrollment included females who were pregnant or breastfeeding and conditions that prevented performing study investigations. Participants who met the inclusion criteria underwent a complete ophthalmological examination by an ocular surface specialist (CLK). AS-OCT was performed at the initial and follow-up visits, with impression cytology and/or biopsy for histology at the initial visit or the time of surgery.
1. Slit lamp examination and imaging procedure
<ol>
	<li>Ask the subject to sit behind the slit lamp. Explain the testing procedures to the subject.</li>
	<li>Edit the subject&#39;s information.</li>
	<li>Disinfect the setup: Wipe down the slit lamp head and chinrest with an alcohol swab.</li>
	<li>Position the subject for examination.
	<ol>
		<li>Ask the subject to place their chin on the chinrest. Instruct the subject to rotate their eyeball to fully expose the lesion. Observe the lesion under the slit lamp.</li>
		<li>Note details of the lesion during the clinical examination, such as laterality, appearance, quadratic location, extent of ocular surface involvement, dimensions of the lesion, presence of keratin, pigmentation, intrinsic vascularity, feeder vessels, cystoid spaces, and scleral involvement.</li>
		<li>Flip the eyelids to observe whether fornical or palpebral conjunctiva are affected.</li>
	</ol>
	</li>
	<li>Perform anterior segment photography with the slit lamp to document clinical features.</li>
</ol>
2. Imaging in the HR-OCT device
NOTE: The following is a general procedure for acquiring anterior segment OCT images scanned by the Fourier-domain optical coherence tomography system (see Table of Materials), which has an axial resolution of 5 &#181;m, transverse resolution of 8 &#181;m, and a scanning speed of 26,000 A-scans/s. To ensure image quality, spectral-domain OCT with shorter wavelengths of light, such as HR-OCT (in-depth resolution of 5-7 &#181;m) or ultra-high-resolution OCT (in-depth resolution of about 2-3 &#181;m), is recommended to better visualize the features of ocular lesions.
<ol>
	<li>Ask the subject to sit behind the imaging device. Explain the testing procedures to the subject.</li>
	<li>Double-click on the RTVue icon to start the.</li>
	<li>Edit the subject&#39;s information.
	<ol>
		<li>Click on the New Patient button to create a new patient. Fill out the information fields, such as last name, first name, gender, birth date, and ethnicity. Click on the Save button.</li>
	</ol>
	</li>
	<li>Disinfect the setup: Wipe down the OCT head and chinrest with an alcohol swab.</li>
	<li>Select the desired scan pattern by clicking on the Cornea &#60; Cross Line button.</li>
	<li>Attach the anterior segment lens to the system scanner.</li>
	<li>Select the eye(s) to be scanned according to the anterior segment slit lamp photography.</li>
	<li>Position the subject for imaging.
	<ol>
		<li>Ask the subject to place their chin on the chinrest. Instruct the subject to roll the eyeball to fully expose the ocular surface lesion.</li>
		<li>Align the lesion of interest with the center of the scan. Click on the Scan tab.</li>
	</ol>
	</li>
	<li>Press Auto P tab&#160;to enhance signal strength. Adjust the scanner head to get the best ocular image. Capture the image using the 8&#215;8 mm automated segmentation OCT scan.</li>
	<li>Review the OCT slices. Click the Save tab to save the scan.</li>
</ol>
3. Determining the region of interest (ROI)
<ol>
	<li>Observe the dynamic sectional view during alignment. Align the cross line with the thickest point of the lesion and capture the scan.</li>
	<li>Pay attention to the adjacent parts of normal and abnormal tissue. Capture the border of the lesion.</li>
</ol>
4. OCT image analysis
NOTE: Evaluate the AS-OCT parameters, such as lesion location (epithelium, subepithelium, or sclera), epithelium reflectivity and thickness, abrupt transition zone from normal to abnormal tissue, visibility of the separation zone between epithelial and subepithelial layers, lesion uniformity, cystoid spaces presence, back-shadowing presence, tumor&#39;s posterior extent delineation, and underlying sclera visibility.
<ol>
	<li>Open the system software and navigate to the Measuring Tools section. Click on the View B-Scans &#60; measuring tool.</li>
	<li>Within the Measuring Tools, select the Distance Tool &#60; measuring tool. Measure the maximal epithelial and sub-epithelial thickness values of the lesion.
	<ol>
		<li>Begin by choosing an initial point on the anterior epithelium boundary, then move vertically to the visible separation between the epithelial and subepithelial layers. Save the maximal area measurement data as epithelial thickness.</li>
		<li>Next, select an anchor point on the visible separation between the epithelial and subepithelial layers, then proceed vertically to the posterior border of the lesion (typically the anterior boundary of the sclera). Save the maximal area measurement data as subepithelial thickness.</li>
	</ol>
	</li>
	<li>Click on&#160;Snapshot Tool&#160;&#60; measuring tool to export a .jpg image of the measurement report screen.</li>
</ol>
5. Follow up procedures
NOTE: Perform OCT examinations monthly during topical chemotherapy and at each follow-up visit following surgical resection and medical or para-surgical treatments.
<ol>
	<li>Slit lamp examination (repeat step 1): Observe and document the changes in the lesion.</li>
	<li>Perform AS-OCT examination.
	<ol>
		<li>Open the system software and locate the existing patient by typing their Name or Birth Date in the &#34;Search By&#34; space. Input the patient&#39;s relevant information and click on the Search button.</li>
		<li>Once the patient is located, click on their name to list all the visits. Choose the &#34;latest visit&#34; and review the OCT images.</li>
		<li>Click on the SCAN button to obtain the current AS-OCT image and assess the parameters on AS-OCT (repeat step 2 to Step 4).</li>
	</ol>
	</li>
</ol>

Evaluating Ocular Surface Squamous Neoplasia Using Anterior Segment HR-OCT

<ol>
	<li>Cicinelli, M. V., Marchese, A., Bandello, F., Modorati, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+management+of+ocular+surface+squamous+neoplasia:+A+review+of+the+current+evidence.">Clinical management of ocular surface squamous neoplasia: A review of the current evidence.</a> Ophthalmol Ther. 7 (2), 247-262 (2018).</li><li>Atallah, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+high-resolution+optical+coherence+tomography+in+diagnosing+ocular+surface+squamous+neoplasia+with+coexisting+ocular+surface+diseases.">Role of high-resolution optical coherence tomography in diagnosing ocular surface squamous neoplasia with coexisting ocular surface diseases.</a> Ocul Surf. 15 (4), 688-695 (2017).</li><li>Venkateswaran, N., Sripawadkul, W., Karp, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+role+of+imaging+technologies+for+ocular+surface+tumors.">The role of imaging technologies for ocular surface tumors.</a> Curr Opin Ophthalmol. 32 (4), 369-378 (2021).</li><li>H&#1255;llhumer, R., Michelow, P., Williams, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+non-invasive+diagnostic+modalities+for+ocular+surface+squamous+neoplasia+at+a+tertiary+hospital,+south+Africa.">Comparison of non-invasive diagnostic modalities for ocular surface squamous neoplasia at a tertiary hospital, south Africa.</a> Eye. 38, 1118-1124 (2023).</li><li>Nguena, M. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnosing+ocular+surface+squamous+neoplasia+in+East+Africa:+Case-control+study+of+clinical+and+in+vivo+confocal+microscopy+assessment.">Diagnosing ocular surface squamous neoplasia in East Africa: Case-control study of clinical and in vivo confocal microscopy assessment.</a> Ophthalmology. 121 (2), 484-491 (2014).</li><li>Tole, D. M., McKelvie, P. A., Daniell, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reliability+of+impression+cytology+for+the+diagnosis+of+ocular+surface+squamous+neoplasia+employing+the+biopore+membrane.">Reliability of impression cytology for the diagnosis of ocular surface squamous neoplasia employing the biopore membrane.</a> Br J Ophthalmol. 85 (2), 154-158 (2001).</li><li>Meel, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ocular+surface+squamous+neoplasia+with+intraocular+extension:+Clinical+and+ultrasound+biomicroscopic+findings.">Ocular surface squamous neoplasia with intraocular extension: Clinical and ultrasound biomicroscopic findings.</a> Ocul Oncol Pathol. 5 (2), 122-127 (2019).</li><li>Singh, S., Mittal, R., Ghosh, A., Tripathy, D., Rath, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-resolution+anterior+segment+optical+coherence+tomography+in+intraepithelial+versus+invasive+ocular+surface+squamous+neoplasia.">High-resolution anterior segment optical coherence tomography in intraepithelial versus invasive ocular surface squamous neoplasia.</a> Cornea. 37 (10), 1292-1298 (2018).</li><li>Huang, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optical+coherence+tomography.">Optical coherence tomography.</a> Science. 254 (5035), 1178-1181 (1991).</li><li>Vempuluru, V. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spectrum+of+as-oct+features+of+ocular+surface+tumors+and+correlation+of+clinico-tomographic+features+with+histopathology:+A+study+of+70+lesions.">Spectrum of as-oct features of ocular surface tumors and correlation of clinico-tomographic features with histopathology: A study of 70 lesions.</a> Int Ophthalmol. 41 (11), 3571-3586 (2021).</li><li>Carol, L. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evolving+technologies+for+lid+and+ocular+surface+neoplasias:+Is+optical+biopsy+a+reality.">Evolving technologies for lid and ocular surface neoplasias: Is optical biopsy a reality.</a> JAMA Ophthalmol. 135 (8), 852-853 (2017).</li><li>Kieval, J. Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultra-high+resolution+optical+coherence+tomography+for+differentiation+of+ocular+surface+squamous+neoplasia+and+pterygia.">Ultra-high resolution optical coherence tomography for differentiation of ocular surface squamous neoplasia and pterygia.</a> Ophthalmology. 119 (3), 481-486 (2012).</li><li>Nanji, A. A., Sayyad, F. E., Galor, A., Dubovy, S., Karp, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-resolution+optical+coherence+tomography+as+an+adjunctive+tool+in+the+diagnosis+of+corneal+and+conjunctival+pathology.">High-resolution optical coherence tomography as an adjunctive tool in the diagnosis of corneal and conjunctival pathology.</a> Ocul Surf. 13 (3), 226-235 (2015).</li><li>Thomas, B. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultra+high-resolution+anterior+segment+optical+coherence+tomography+in+the+diagnosis+and+management+of+ocular+surface+squamous+neoplasia.">Ultra high-resolution anterior segment optical coherence tomography in the diagnosis and management of ocular surface squamous neoplasia.</a> Ocul Surf. 12 (1), 46-58 (2014).</li><li>Venkateswaran, N., Mercado, C., Galor, A., Karp, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+topical+5-fluorouracil+and+interferon+alfa-2b+as+primary+treatment+modalities+for+ocular+surface+squamous+neoplasia.">Comparison of topical 5-fluorouracil and interferon alfa-2b as primary treatment modalities for ocular surface squamous neoplasia.</a> Am J Ophthalmol. 199, 216-222 (2019).</li><li>Tran, A. Q., Venkateswaran, N., Galor, A., Karp, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Utility+of+high-resolution+anterior+segment+optical+coherence+tomography+in+the+diagnosis+and+management+of+sub-clinical+ocular+surface+squamous+neoplasia.">Utility of high-resolution anterior segment optical coherence tomography in the diagnosis and management of sub-clinical ocular surface squamous neoplasia.</a> Eye Vis (Lond). 6, 27 (2019).</li><li>Stevens, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+and+optical+coherence+tomography+comparison+between+ocular+surface+squamous+neoplasia+and+squamous+metaplasia.">Clinical and optical coherence tomography comparison between ocular surface squamous neoplasia and squamous metaplasia.</a> Cornea. 42 (4), 429-434 (2022).</li><li>Theotoka, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+high-resolution+optical+coherence+tomography+(HR-OCT)+in+the+diagnosis+of+ocular+surface+masqueraders.">The use of high-resolution optical coherence tomography (HR-OCT) in the diagnosis of ocular surface masqueraders.</a> Ocul Surf. 24, 74-82 (2022).</li></ol>

The authors have nothing to disclose.

Anterior segment OCT (AS-OCT) is a promising diagnostic tool for surveying the ocular surface. It obtains an optical section of the ocular surface following the principle of Michelson&#39;s interferometry9. The systematic interpretation of AS-OCT begins with the outmost tissue of the ocular surface, namely the epithelium of the cornea, limbal, and conjunctival complex.A recent study by Vempuluru et al. showed that AS-OCT is very useful in confirming epithelial involvement where most ocular surface...

Ocular surface squamous neoplasia (OSSN) is the most common non-pigmented tumor of the conjunctiva and cornea. The term OSSN encompasses a broad spectrum of squamous neoplastic changes, including dysplasia (graded I-III), intraepithelial neoplasia (i.e., carcinoma in situ, CIS), and invasive squamous cell carcinoma (SCC)1. The diagnosis of OSSN can be made clinically by slit lamp examination by detecting the typical appearance of elevated, leukoplakic or papilliform mass, often presented at limbus straddling conjunctiva to the cornea with feeder vessels2. Sometimes, they may present less distinctively. The gold standard for the diagnosis of OSSN remains histopathologic confirmation followed by incisional or excisional biopsy1,3. 
Recently, the therapeutic pattern of OSSN has shifted from surgical management to the use of topical chemotherapy. This has greatly promoted the adoption of biopsy to less or non-invasive modalities4. Various imaging devices have been studied for the characterization of OSSN, namely HR-OCT, in vivo confocal microscopy (IVCM)5, impression cytology (IC)6, ultrasound biomicroscopy (UBM)7, and methylene blue stain4. Currently, several studies have provided insights into the characterization of OSSN using anterior segment HR-OCT. Commercially available HR-OCT devices using spectral-domain technology can attain an axial resolution of approximately 5 &#181;m. These images provide in vivo, cross-sectional views of ocular surface lesions and display distinct features of OSSN that parallel the changes seen in histopathology. Hence, HR-OCT enables clinicians to obtain an "optical biopsy" to expediently diagnose and monitor OSSN in clinics.
To promote the application of HR-OCT in the management of OSSN, a standardized, practical, and reproducible guidance for image acquisition is presented in detail to ensure good quality for clinical use. Also, characteristics of OSSN and other common benign lesions on HR-OCT are elucidated for better image interpretation.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>70% Ethanol</td>
			<td>Any make</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Fourier-domain optical coherence tomography (OCT) system</td>
			<td>Optuvue Inc., Fremont, CA, USA</td>
			<td>RTVue XR</td>
			<td></td>
		</tr>
		<tr>
			<td>RTVue software</td>
			<td>Optuvue Inc., Fremont, CA, USA</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

anterior high-resolution optical coherence tomography in the diagnosis and therapeutic monitoring of ocular surface squamous neoplasia

Ocular surface squamous neoplasia (OSSN) is the most common tumor of the ocular surface, ranging from mild dysplasia to invasive squamous carcinoma. Traditionally, the diagnosis of OSSN relies on histopathological confirmation followed by a full-thickness biopsy. However, in the past two decades, the therapeutic approach to OSSN has shifted from surgical intervention to topical chemotherapy regimens in clinical settings. This shift emphasizes the need for less invasive or non-invasive methods to diagnose ocular surface pathologies. Among various imaging devices, commercially available high-resolution optical coherence tomography (HR-OCT) has emerged as a powerful tool for the characterization of OSSN. HR-OCT provides an in vivo, cross-sectional view of ocular surface lesions, offering an "optical biopsy" for OSSN with high sensitivity and specificity. It provides valuable information in differentiating intraepithelial or invasive OSSN from other benign lesions. Additionally, HR-OCT can be used to monitor the response to topical chemotherapy and to detect subclinical OSSN during follow-up visits. In this article, the scanning protocol for image acquisition is presented, and image interpretation for OSSN is outlined. This standardized, practical, and reproducible approach is recommended in clinical workflows and is expected to assist clinicians in the management of OSSN.

Figure 1A,B illustrate HR-OCT images of OSSN, revealing three key characteristics: (1) Significantly thickened hyper-reflective epithelium; (2) An abrupt shift from normal to abnormal epithelium, marked by a sudden rise in both brightness and thickness of the epithelium; (3) Occasionally, a division plane is visible between the epithelium and underlying tissue. However, in very thick lesions, the lower edge of the lesion may be somewhat obscured by shadowing.
<p class="j...

Author Spotlight: Anterior HR-OCT as a Non-Invasive Tool for Characterizing Ocular Surface Squamous Neoplasia

Anterior segment high-resolution optical coherence tomography (HR-OCT) is a promising non-invasive modality for the diagnosis and therapeutic evaluation of ocular surface squamous neoplasia (OSSN). Here, the system setup, scanning technique, and representative diagnostic results are presented.

Anterior High-Resolution Optical Coherence Tomography in the Diagnosis and Therapeutic Monitoring of Ocular Surface Squamous Neoplasia

Ocular surface squamous neoplasia (OSSN) is the most common tumor of the ocular surface, ranging from mild dysplasia to invasive squamous carcinoma. ...

anterior-high-resolution-optical-coherence-tomography-diagnosis

Research

JoVE Journal

Engineering

884 Views.  the First Affiliated Hospital of Harbin Medical University. En hier is een optische coherentietomografie met hoge resolutie, of HROCT, een veelbelovend hulpmiddel voor het niet-invasief karakteriseren van schermfouten op het oogoppervlak, neoplasie of OSSN. Het biedt een in-vivo transsectioneel volume van ocululaire oppervlaklaesies en biedt een optische biopsie. Voor OSSN presenteerden we een gestandaardiseerde, praktische, reproduceerbare aanpak om clinici te helpen bij het beheren van OSSN in klinische workflows.

Video: Auteur in de schijnwerpers: anterieure HR-OCT als een niet-invasief hulpmiddel voor het karakteriseren van plaveiselcelneoplasie op het oogoppervlak

Fabricating Metamaterials Using the Fiber Drawing Method

Metamaterials are man-made composite materials, fabricated by assembling components much smaller than the wavelength at which they operate 1. They owe their electromagnetic properties to the structure of their constituents, instead of the atoms that compose them. For example, sub-wavelength metal wires can be arranged to possess an effective electric permittivity that is either positive or negative at a given frequency, in contrast to the metals themselves 2. This unprecedented control over the behaviour of light can potentially lead to a number of novel devices, such as invisibility cloaks 3, negative refractive index materials 4, and lenses that resolve objects below the diffraction limit 5. However, metamaterials operating at optical, mid-infrared and terahertz frequencies are conventionally made using nano- and micro-fabrication techniques that are expensive and produce samples that are at most a few centimetres in size 6-7. Here we present a fabrication method to produce hundreds of meters of metal wire metamaterials in fiber form, which exhibit a terahertz plasmonic response 8. We combine the stack-and-draw technique used to produce microstructured polymer optical fiber 9 with the Taylor-wire process 10, using indium wires inside polymethylmethacrylate (PMMA) tubes. PMMA is chosen because it is an easy to handle, drawable dielectric with suitable optical properties in the terahertz region; indium because it has a melting temperature of 156.6 &deg;C which is appropriate for codrawing with PMMA. We include an indium wire of 1 mm diameter and 99.99% purity in a PMMA tube with 1 mm inner diameter (ID) and 12 mm outside diameter (OD) which is sealed at one end. The tube is evacuated and drawn down to an outer diameter of 1.2 mm. The resulting fiber is then cut into smaller pieces, and stacked into a larger PMMA tube. This stack is sealed at one end and fed into a furnace while being rapidly drawn, reducing the diameter of the structure by a factor of 10, and increasing the length by a factor of 100. Such fibers possess features on the micro- and nano- scale, are inherently flexible, mass-producible, and can be woven to exhibit electromagnetic properties that are not found in nature. They represent a promising platform for a number of novel devices from terahertz to optical frequencies, such as invisible fibers, woven negative refractive index cloths, and super-resolving lenses.

Metamaterials at terahertz frequencies offer unique opportunities, but are challenging to fabricate in bulk. We adapt the fabrication procedure for microstructured polymer optical fibers to inexpensively fabricate metamaterials potentially on an industrial scale. We produce polymethylmethacrylate fibers containing ~10 &mu;m diameter indium wires separated by ~100 &mu;m, which exhibit a terahertz plasmonic response.

Metamaterials are man-made composite materials, fabricated by assembling components much smaller than the wavelength at which they operate 1. They owe ...

Construction of a High Resolution Microscope with Conventional and Holographic Optical Trapping Capabilities

High resolution microscope systems with optical traps allow for precise manipulation of various refractive objects, such as dielectric beads 1 or cellular organelles 2,3, as well as for high spatial and temporal resolution readout of their position relative to the center of the trap. The system described herein has one such "traditional" trap operating at 980 nm. It additionally provides a second optical trapping system that uses a commercially available holographic package to simultaneously create and manipulate complex trapping patterns in the field of view of the microscope 4,5 at a wavelength of 1,064 nm. The combination of the two systems allows for the manipulation of multiple refractive objects at the same time while simultaneously conducting high speed and high resolution measurements of motion and force production at nanometer and piconewton scale.

The system described herein employs a traditional optical trap as well as an independent holographic optical trapping line, capable of creating and manipulating multiple traps. This allows for the creation of complex geometric arrangements of refractive particles while also permitting simultaneous high-speed, high-resolution measurements of the activity of biological enzymes.

High resolution microscope systems with optical traps allow for precise manipulation of various refractive objects, such as dielectric beads 1 or cellular ...

Picoinjection of Microfluidic Drops Without Metal Electrodes

Existing methods for picoinjecting reagents into microfluidic drops require metal electrodes integrated into the microfluidic chip. The integration of these electrodes adds cumbersome and error-prone steps to the device fabrication process. We have developed a technique that obviates the needs for metal electrodes during picoinjection. Instead, it uses the injection fluid itself as an electrode, since most biological reagents contain dissolved electrolytes and are conductive. By eliminating the electrodes, we reduce device fabrication time and complexity, and make the devices more robust. In addition, with our approach, the injection volume depends on the voltage applied to the picoinjection solution; this allows us to rapidly adjust the volume injected by modulating the applied voltage. We demonstrate that our technique is compatible with reagents incorporating common biological compounds, including buffers, enzymes, and nucleic acids.

We have developed a technique for picoinjecting microfluidic drops that does not require metal electrodes. As such, devices incorporating our technique are simpler to fabricate and to use.

Existing methods for picoinjecting reagents into microfluidic drops require metal electrodes integrated into the microfluidic chip. The integration of ...

Measurement of Coherence Decay in GaMnAs Using Femtosecond Four-wave Mixing

The application of femtosecond four-wave mixing to the study of fundamental properties of diluted magnetic semiconductors ((s,p)-d hybridization, spin-flip scattering) is described, using experiments on GaMnAs as a prototype III-Mn-V system.&#160; Spectrally-resolved and time-resolved experimental configurations are described, including the use of zero-background autocorrelation techniques for pulse optimization.&#160; The etching process used to prepare GaMnAs samples for four-wave mixing experiments is also highlighted.&#160; The high temporal resolution of this technique, afforded by the use of short (20 fsec) optical pulses, permits the rapid spin-flip scattering process in this system to be studied directly in the time domain, providing new insight into the strong exchange coupling responsible for carrier-mediated ferromagnetism.&#160; We also show that spectral resolution of the four-wave mixing signal allows one to extract clear signatures of (s,p)-d hybridization in this system, unlike linear spectroscopy techniques.&#160;&#160; This increased sensitivity is due to the nonlinearity of the technique, which suppresses defect-related contributions to the optical response. This method may be used to measure the time scale for coherence decay (tied to the fastest scattering processes) in a wide variety of semiconductor systems of interest for next generation electronics and optoelectronics.

The technique of femtosecond four-wave mixing is described, including spectrally-resolved and time-resolved configurations. We illustrate the utility of this technique for the investigation of crucial physical properties in the III-V diluted magnetic semiconductors, afforded by its nonlinearity and high temporal resolution.

The application of femtosecond four-wave mixing to the study of fundamental properties of diluted magnetic semiconductors ((s,p)-d hybridization, ...

Taking Advantage of Reduced Droplet-surface Interaction to Optimize Transport of Bioanalytes in Digital Microfluidics

Digital microfluidics (DMF), a technique for manipulation of droplets, is a promising alternative for the development of &#8220;lab-on-a-chip&#8221; platforms. Often, droplet motion relies on the wetting of a surface, directly associated with the application of an electric field; surface interactions, however, make motion dependent on droplet contents, limiting the breadth of applications of the technique.
Some alternatives have been presented to minimize this dependence. However, they rely on the addition of extra chemical species to the droplet or its surroundings, which could potentially interact with droplet moieties. Addressing this challenge, our group recently developed Field-DW devices to allow the transport of cells and proteins in DMF, without extra additives.
Here, the protocol for device fabrication and operation is provided, including the electronic interface for motion control. We also continue the studies with the devices, showing that multicellular, relatively large, model organisms can also be transported, arguably unaffected by the electric fields required for device operation.

The protocol for fabrication and operation of field dewetting devices (Field-DW) is described, as well as the preliminary studies of the effects of electric fields on droplet contents.

Digital microfluidics (DMF), a technique for manipulation of droplets, is a promising alternative for the development of &#8220;lab-on-a-chip&#8221; ...

Patterning via Optical Saturable Transitions - Fabrication and Characterization

This protocol describes the fabrication and characterization of nanostructures using a novel nanolithographic technique called Patterning via Optical Saturable Transitions (POST). In this technique the chemical properties of organic photochromic molecules that undergo single-photon reactions are exploited, enabling rapid top-down nanopatterning over large areas at low light intensities, thereby, allowing for the circumvention of the far-field diffraction barrier.4 Simple, cost-effective, high throughput and resolution alternatives to nanopatterning are being explored, such as, two-photon polymerization5,6, beam pen lithography (BPL)7, scanning electron beam lithography (SEBL), and focused ion beam (FIB) patterning. However, multi-photon approaches require high light intensities, which limit their potential for high throughput and offer low image contrast. Although, electron and ion beam lithographic processes offer increased resolution, the serial nature of the process is limited to slow writing speeds, which also prevents patterning of features over large areas. Beam-pen lithography is an approach towards parallel near-field optical lithography. However, the gap between the source of the beam and the surface of the photoresist needs to be controlled extremely precisely for good pattern uniformity and this is very challenging to accomplish for large arrays of beams. Patterning via Optical Saturable Transitions (POST) is an alternative optical nanopatterning technique for patterning sub-wavelength features1-3. Since this technique uses single photons instead of electrons, it is extremely fast and does not require high light intensities1-3, opening the door to massive parallelization.

We report that the diffraction limit of conventional optical lithography can be overcome by exploiting the transitions of organic photochromic derivatives induced by their photoisomerization at low light intensities.1-3 This paper outlines our fabrication technique and two locking mechanisms, namely: dissolution of one photoisomer and electrochemical oxidation.

This protocol describes the fabrication and characterization of nanostructures using a novel nanolithographic technique called Patterning via Optical ...

Quantification of Hydrogen Concentrations in Surface and Interface Layers and Bulk Materials through Depth Profiling with Nuclear Reaction Analysis

Nuclear reaction analysis (NRA) via the resonant 1H(15N,&#945;&#947;)12C reaction is a highly effective method of depth profiling that quantitatively and non-destructively reveals the hydrogen density distribution at surfaces, at interfaces, and in the volume of solid materials with high depth resolution. The technique applies a 15N ion beam of 6.385 MeV provided by an electrostatic accelerator and specifically detects the 1H isotope in depths up to about 2 &#956;m from the target surface. Surface H coverages are measured with a sensitivity in the order of ~1013 cm-2 (~1% of a typical atomic monolayer density) and H volume concentrations with a detection limit of ~1018 cm-3 (~100 at. ppm). The near-surface depth resolution is 2-5 nm for surface-normal 15N ion incidence onto the target and can be enhanced to values below 1 nm for very flat targets by adopting a surface-grazing incidence geometry. The method is versatile and readily applied to any high vacuum compatible homogeneous material with a smooth surface (no pores). Electrically conductive targets usually tolerate the ion beam irradiation with negligible degradation. Hydrogen quantitation and correct depth analysis require knowledge of the elementary composition (besides hydrogen) and mass density of the target material. Especially in combination with ultra-high vacuum methods for in-situ target preparation and characterization, 1H(15N,&#945;&#947;)12C NRA is ideally suited for hydrogen analysis at atomically controlled surfaces and nanostructured interfaces. We exemplarily demonstrate here the application of 15N NRA at the MALT Tandem accelerator facility of the University of Tokyo to (1) quantitatively measure the surface coverage and the bulk concentration of hydrogen in the near-surface region of a H2 exposed Pd(110) single crystal, and (2) to determine the depth location and layer density of hydrogen near the interfaces of thin SiO2 films on Si(100).

We illustrate the application of 1H(15N,&#945;&#947;)12C resonant nuclear reaction analysis (NRA) to quantitatively evaluate the density of hydrogen atoms on the surface, in the volume, and at an interfacial layer of solid materials. The near-surface hydrogen depth profiling of a Pd(110) single crystal and of SiO2/Si(100) stacks is described.

Nuclear reaction analysis (NRA) via the resonant 1H(15N,&#945;&#947;)12C reaction is a highly effective method of depth profiling that quantitatively and ...

High Resolution Phonon-assisted Quasi-resonance Fluorescence Spectroscopy

High resolution optical spectroscopy methods are demanding in terms of either technology, equipment, complexity, time or a combination of these. Here we demonstrate an optical spectroscopy method that is capable of resolving spectral features beyond that of the spin fine structure and homogeneous linewidth of single quantum dots (QDs) using a standard, easy-to-use spectrometer setup. This method incorporates both laser and photoluminescence spectroscopy, combining the advantage of laser line-width limited resolution with multi-channel photoluminescence detection. Such a scheme allows for considerable improvement of resolution over that of a common single-stage spectrometer. The method uses phonons to assist in the measurement of the photoluminescence of a single quantum dot after resonant excitation of its ground state transition. The phonon&#39;s energy difference allows one to separate and filter out the laser light exciting the quantum dot. An advantageous feature of this method is its straight forward integration into standard spectroscopy setups, which are accessible to most researchers.

The manuscript describes a method of phonon-assisted quasi-resonant fluorescence spectroscopy that incorporates both laser-limited resolution and photoluminescence (PL) spectroscopy. This method utilizes optical phonons to provide linewidth-limited resolution spectra of atom-like semiconductor structures in the energy domain. The method is also easily realized with a single spectrometer optical spectroscopy setup.

High resolution optical spectroscopy methods are demanding in terms of either technology, equipment, complexity, time or a combination of these. Here we ...

Emission Spectroscopic Boundary Layer Investigation during Ablative Material Testing in Plasmatron

Ablative Thermal Protection Systems (TPS) allowed the first humans to safely return to Earth from the moon and are still considered as the only solution for future high-speed reentry missions. But despite the advancements made since Apollo, heat flux prediction remains an imperfect science and engineers resort to safety factors to determine the TPS thickness. This goes at the expense of embarked payload, hampering, for example, sample return missions. 
Ground testing in plasma wind-tunnels is currently the only affordable possibility for both material qualification and validation of material response codes. The subsonic 1.2MW Inductively Coupled Plasmatron facility at the von Karman Institute for Fluid Dynamics is able to reproduce a wide range of reentry environments. This protocol describes a procedure for the study of the gas/surface interaction on ablative materials in high enthalpy flows and presents sample results of a non-pyrolyzing, ablating carbon fiber precursor. With this publication, the authors envisage the definition of a standard procedure, facilitating comparison with other laboratories and contributing to ongoing efforts to improve heat shield reliability and reduce design uncertainties.
The described core techniques are non-intrusive methods to track the material recession with a high-speed camera along with the chemistry in the reactive boundary layer, probed by emission spectroscopy. Although optical emission spectroscopy is limited to line-of-sight measurements and is further constrained to electronically excited atoms and molecules, its simplicity and broad applicability still make it the technique of choice for analysis of the reactive boundary layer. Recession of the ablating sample further requires that the distance of the measurement location with respect to the surface is known at all times during the experiment. Calibration of the optical system of the applied three spectrometers allowed quantitative comparison. At the fiber scale, results from a post-test microscopy analysis are presented.

Development of new ablative materials and their numerical modeling requires extensive experimental investigation. This protocol describes procedures for material response characterization in plasma flows with the core techniques being non-intrusive methods to track the material recession along with the chemistry in the reactive boundary layer by emission spectroscopy.

Ablative Thermal Protection Systems (TPS) allowed the first humans to safely return to Earth from the moon and are still considered as the only solution ...

High-resolution Thermal Micro-imaging Using Europium Chelate Luminescent Coatings

Micro-electronic devices often undergo significant self-heating when biased to their typical operating conditions. This paper describes a convenient optical micro-imaging technique which can be used to map and quantify such behavior. Europium thenoyltrifluoroacetonate (EuTFC) has a 612 nm luminescence line whose activation efficiency drops strongly with increasing temperature, due to T-dependent interactions between the Eu3+ ion and the organic chelating compound. This material may be readily coated on to a sample surface by thermal sublimation in vacuum. When the coating is excited with ultraviolet light (337 nm) an optical micro-image of the 612 nm luminescent response can be converted directly into a map of the sample surface temperature. This technique offers spatial resolution limited only by the microscope optics (about 1 micron) and time resolution limited by the speed of the camera employed. It offers the additional advantages of only requiring comparatively simple and non-specialized equipment, and giving a quantitative probe of sample temperature.

Europium thenoyltrifluoroacetonate (EuTFC) has an optical luminescence line at 612 nm, whose activation efficiency decreases strongly with temperature. If a sample coated with a thin film of this material is micro-imaged, the 612 nm luminescent response intensity may be converted into a direct map of sample surface temperature.

Micro-electronic devices often undergo significant self-heating when biased to their typical operating conditions. This paper describes a convenient ...

Anterior High-Resolution Optical Coherence Tomography in the Diagnosis and Therapeutic Monitoring of Ocular Surface Squamous Neoplasia

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