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10 pages, 3639 KiB  
Article
On-Chip DNA Assembly via Dielectrophoresis
by Xichuan Rui, Lin-Sheng Wu and Xin Zhao
Micromachines 2025, 16(1), 76; https://doi.org/10.3390/mi16010076 (registering DOI) - 11 Jan 2025
Viewed by 226
Abstract
On-chip gene synthesis has the potential to improve the synthesis throughput and reduce the cost exponentially. While there exist several microarray-based oligo synthesis technologies, on-chip gene assembly has yet to be demonstrated. This work introduces a novel on-chip DNA assembly method via dielectrophoresis [...] Read more.
On-chip gene synthesis has the potential to improve the synthesis throughput and reduce the cost exponentially. While there exist several microarray-based oligo synthesis technologies, on-chip gene assembly has yet to be demonstrated. This work introduces a novel on-chip DNA assembly method via dielectrophoresis (DEP) that can potentially be integrated with microarray-based oligo synthesis on the same chip. Our DEP chip can selectively manipulate oligos and guide their movement without perturbing the surrounding fluid medium, thus aiding in DNA assembly. Helical forked electrode design has been optimized for compatibility with DEP, ensuring efficient control over target oligos. By applying an alternating current signal set at 2 MHz, we successfully achieve the desired directed movement of oligonucleotides. Additionally, chemical treatments combined with photoirradiation enabled the connection of complementary gene sequences and the subsequent release of single-stranded DNA products. Sequencing results validate the effective assembly of DNA fragments, approximately 500 base pairs in length, using our DEP device. Full article
(This article belongs to the Collection Micro/Nanoscale Electrokinetics)
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Figure 1

Figure 1
<p>Schematic of the DEP device for gene synthesis. (<b>a</b>) The chemical modification of the DEP electrode allows DBCO-PC linker-Oligos to bond to the chip. (<b>b</b>) N3-PEG-Mal reacts with Oligos on the electrode surface, resulting in the formation of Oligos. (<b>c</b>) Oligos manipulation occurs on the electrode surface through DEP forces. (<b>d</b>) By applying an AC signal, complementary pairing takes place between the free oligos and the bonded oligos on the electrode. Unpaired oligos are washed away, and controlled light exposure facilitates the release of the target dsDNA, ultimately producing the desired target dsDNA.</p>
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<p>Experimental observation of DNA enrichment on the right electrode. The experiment was conducted under an alternating current power supply (2 MHz, 50 Vrms). The electrode width is 25 µm, and the distance between sub-electrodes is 25 μm, corresponding to a DNA concentration of 20 ng/µL. The data results have been treated with normalization (Scale bar: 200 μm).</p>
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<p>The graph depicts the change in fluorescence intensity over time when DNA is driven by DEP forces. An AC signal was applied to the right electrode, leading to a significant enhancement in the fluorescence signal on the right side. Upon switching the AC signal to the left electrode, a noticeable increase in the signal on the left side occurred, accompanied by a concurrent decrease in the fluorescence signal on the right side.</p>
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<p>COMSOL Multiphysics<sup>®</sup> software is employed for simulating the DEP electrodes, with specific parameters allowing individual control of the electrode at a frequency of 2 MHz. This enables the polarization and manipulation of DNA on the electrode.</p>
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<p>Gel electrophoresis image of 2% agarose gel for double-stranded DNA. The DNA was obtained through electrophoresis-driven complementary pairing of single-stranded DNA, indicating that the length of the DNA is approximately in the 500 bp range.</p>
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<p>Schematic of the DEP device (<b>a</b>) helical forked electrode design. Four electrodes are arranged in an alternating circular pattern. All electrodes have a width of D1, and the distance between the two sets of electrodes is L1. When AC voltage is applied to the electrodes, the oligos in the aqueous solution on the electrodes experience sufficient DEP force to induce movement. (<b>b</b>) Side view of the single-plane DEP structure.</p>
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<p>Microfluidic ink cartridge containing the DEP chip, along with the signal generator and high-voltage amplifier equipment for applying DEP forces.</p>
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15 pages, 2539 KiB  
Article
Production of Hydrophobic Microparticles at Safe-To-Inject Sizes for Intravascular Administration
by Francisca L. Gomes, Francisco Conceição, Liliana Moreira Teixeira, Jeroen Leijten and Pascal Jonkheijm
Pharmaceutics 2025, 17(1), 64; https://doi.org/10.3390/pharmaceutics17010064 - 6 Jan 2025
Viewed by 368
Abstract
Background/Objectives: Hydrophobic microparticles are one of the most versatile structures in drug delivery and tissue engineering. These constructs offer a protective environment for hydrophobic or water-sensitive compounds (e.g., drugs, peroxides), providing an optimal solution for numerous biomedical purposes, such as drug delivery or [...] Read more.
Background/Objectives: Hydrophobic microparticles are one of the most versatile structures in drug delivery and tissue engineering. These constructs offer a protective environment for hydrophobic or water-sensitive compounds (e.g., drugs, peroxides), providing an optimal solution for numerous biomedical purposes, such as drug delivery or oxygen therapeutics. The intravascular administration of hydrophobic microparticles requires a safe-to-flow particle profile, which typically corresponds to a maximum size of 5 µm—the generally accepted diameter for the thinnest blood vessels in humans. However, the production of hydrophobic microparticles below this size range remains largely unexplored. In this work, we investigate the fabrication of hydrophobic microparticles at safe-to-inject and safe-to-flow sizes (<5 µm) for intravascular administration. Methods: Polycaprolactone microparticles (PCL MPs) are produced using a double-emulsification method with tip ultrasonication, for which various production parameters (PCL molecular weight, PCL concentration, type of stabilizer, and filtration) are optimized to obtain particles at sizes below 5 µm. Results: We achieve a PCL MP size distribution of 99.8% below this size limit, and prove that these particles can flow without obstruction through a microfluidic model emulating a thin human blood capillary (4.1 µm × 3.0 µm width × heigh). Conclusions: Overall, we demonstrate that hydrophobic microparticles can be fabricated at safe-to-flow sizes using a simple and scalable setup, paving the way towards their applicability as new intravascular injectables. Full article
(This article belongs to the Special Issue Microemulsion Utility in Pharmaceuticals)
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Graphical abstract

Graphical abstract
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<p>Schematic depiction of the double-emulsification process, with tip ultrasonication, to produce PCL MPs.</p>
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<p>(<b>a</b>–<b>f</b>) Screening for the effect of PCL MW, type of stabilizer, and membrane filtering on the size distribution of PCL MPs. The conditions were achieved with PCL 80 kDa (<b>a</b>,<b>b</b>), 45 kDa (<b>c</b>,<b>d</b>) or 10 kDa (<b>e</b>,<b>f</b>), and stabilized with 0.3% <span class="html-italic">w</span>/<span class="html-italic">v</span> PVA (<b>a</b>,<b>c</b>,<b>e</b>) or 1% <span class="html-italic">w</span>/<span class="html-italic">v</span> gelatin (<b>b</b>,<b>d</b>,<b>f</b>). The dark bars indicate no filtering, the light bars indicate 5 µm cut-off filtering. Dashed lines indicate the 5 µm cut-off.</p>
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<p>Percentage of PCL MPs below 5 µm in diameter for different production conditions. Dark dots indicate unfiltered batches, light dots indicate filtered batches. Green circle indicates a size distribution of 100% below 5 µm.</p>
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<p>(<b>a</b>,<b>b</b>) Screening for the effect of PCL concentration (3%, 5%, 10% <span class="html-italic">w</span>/<span class="html-italic">v</span>) on size distribution (<b>a</b>) and zeta potential (<b>b</b>) of PCL MPs produced using 0.3% <span class="html-italic">w</span>/<span class="html-italic">v</span> PVA and PCL 10 kDa. (<b>c</b>) Optical micrograph of PCL MPs. Scale bar equals 10 µm. (<b>d</b>) The scanning electron micrograph of PCL MPs. Scale bar equals 5 µm, the original SEM image can be found in <a href="#app1-pharmaceutics-17-00064" class="html-app">Figure S1</a>. (<b>e</b>) The particle size distribution of PCL MPs based on optical microscopy. Data collected for n = 3 batches. (<b>f</b>) The summary of particle size, coefficient of variation, and percentage of particles below 5 µm. The dashed line indicates 5 µm cut-off.</p>
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<p>(<b>a</b>) Schematic depiction of a blood capillary network. (<b>b</b>) Schematic depiction of chip design for a microfluidics model of a thin blood capillary. (<b>c</b>) Epifluorescence image of a PCL MP (stained with DiOC<sub>6,</sub> in green) during flow. The arrows indicate particles. The scale bar equals 10 µm. (<b>d</b>) An epifluorescence image of a microfluidics model simulating a thin blood capillary upon complete flow of PCL MPs (stained in green). The scale bar equals 10 µm.</p>
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<p>(<b>a</b>) Schematic depiction of optimized PCL MPs. (<b>b</b>) Safe-to-inject concentrations for PCL MPs at different product volumes. Concentration of erythrocytes in a unit of blood represented as reference. (<b>c</b>) Calculated cargo load for different encapsulation efficiency rates.</p>
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12 pages, 2636 KiB  
Article
MoTe2 Photodetector for Integrated Lithium Niobate Photonics
by Qiaonan Dong, Xinxing Sun, Lang Gao, Yong Zheng, Rongbo Wu and Ya Cheng
Nanomaterials 2025, 15(1), 72; https://doi.org/10.3390/nano15010072 - 5 Jan 2025
Viewed by 383
Abstract
The integration of a photodetector that converts optical signals into electrical signals is essential for scalable integrated lithium niobate photonics. Two-dimensional materials provide a potential high-efficiency on-chip detection capability. Here, we demonstrate an efficient on-chip photodetector based on a few layers of MoTe [...] Read more.
The integration of a photodetector that converts optical signals into electrical signals is essential for scalable integrated lithium niobate photonics. Two-dimensional materials provide a potential high-efficiency on-chip detection capability. Here, we demonstrate an efficient on-chip photodetector based on a few layers of MoTe2 on a thin film lithium niobate waveguide and integrate it with a microresonator operating in an optical telecommunication band. The lithium-niobate-on-insulator waveguides and micro-ring resonator are fabricated using the femtosecond laser photolithography-assisted chemical–mechanical etching method. The lithium niobate waveguide-integrated MoTe2 presents an absorption coefficient of 72% and a transmission loss of 0.27 dB µm−1 at 1550 nm. The on-chip photodetector exhibits a responsivity of 1 mA W−1 at a bias voltage of 20 V, a low dark current of 1.6 nA, and a photo–dark current ratio of 108 W−1. Due to effective waveguide coupling and interaction with MoTe2, the generated photocurrent is approximately 160 times higher than that of free-space light irradiation. Furthermore, we demonstrate a wavelength-selective photonic device by integrating the photodetector and micro-ring resonator with a quality factor of 104 on the same chip, suggesting potential applications in the field of on-chip spectrometers and biosensors. Full article
(This article belongs to the Section Nanofabrication and Nanomanufacturing)
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Figure 1

Figure 1
<p>(<b>a</b>) Schematic diagram of the MoTe<sub>2</sub>-based on-chip photodetector. (<b>b</b>) Raman spectrum of 2H-MoTe<sub>2</sub> (20 layers) on the LNOI platform under 532 nm laser excitation. Insert schematic of the MoTe<sub>2</sub> structure: Mo (purple) and Te (yellow), the arrows indicate the direction of atom vibration. (<b>c</b>) AFM image of 2H-MoTe<sub>2</sub> covering the LNOI waveguide (WG). (<b>d</b>) The thickness of the 2H-MoTe<sub>2</sub> layer corresponds to the region of the solid line (red color) marked in (<b>c</b>).</p>
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<p>Simulation of the light field distribution in the LNOI waveguide without 2H-MoTe<sub>2</sub> (<b>a</b>) and with 2H-MoTe<sub>2</sub> (<b>b</b>). (<b>c</b>) The simulation of the electric field intensity |E<sup>2</sup>| in the coupling section for TE polarization. (<b>d</b>) Measured transmission loss of the waveguide without and with 2H-MoTe<sub>2</sub>.</p>
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<p>(<b>a</b>) Schematic band diagrams of the Au-2H-MoTe<sub>2</sub>-Au structure: (<b>top</b>) in thermal equilibrium; (<b>bottom</b>) under illumination and applied bias voltage. (<b>b</b>) Comparison of the I-V curves under dark and in-coupled light intensity with 190 μW. (<b>c</b>) I–V curves at varying light intensities. (<b>d</b>) Photocurrent as a function of light intensity within the waveguide at different bias voltages. (<b>e</b>) Responsivity and EQE as functions of bias voltage. (<b>f</b>) Impulse response curve of the photodetector.</p>
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<p>(<b>a</b>) I–V curves at a constant in-coupled light intensity of 300 μW with different wavelengths. (<b>b</b>) Comparison of the responsivity of the photodetector under in-coupled light via waveguide and spatial illumination. (<b>c</b>) Simulated absorption rate of 2H-MoTe<sub>2</sub> at varying thicknesses. (<b>d</b>) 2H-MoTe<sub>2</sub> thickness-dependent responsivity of on-chip photodetectors.</p>
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<p>(<b>a</b>) Schematic diagram of the PD on a waveguide-coupled ring resonant cavity, the arrows indicate the direction of light propagation. (<b>b</b>) Optical micrograph of the micro-ring resonator (MRR) and the corresponding waveguide-integrated photodetector. (<b>c</b>) Output energy of the waveguide with and without 2H-MoTe<sub>2</sub>. (<b>d</b>) Comparison of transmission spectrum measured using commercial detectors and photocurrent measured using on-chip integrated PD, and Lorentz fitting curve.</p>
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13 pages, 27964 KiB  
Article
Enhanced Terahertz Sensing via On-Chip Integration of Diffractive Optics with InGaAs Bow-Tie Detectors
by Karolis Redeckas, Vytautas Jakštas, Matas Bernatonis, Vincas Tamošiūnas, Gintaras Valušis and Linas Minkevičius
Sensors 2025, 25(1), 229; https://doi.org/10.3390/s25010229 - 3 Jan 2025
Viewed by 326
Abstract
The practical implementation of terahertz (THz) imaging and spectroscopic systems in real operational conditions requires them to be of a compact size, to have enhanced functionality, and to be user-friendly. This work demonstrates the single-sided integration of Fresnel-zone-plate-based optical elements with InGaAs bow-tie [...] Read more.
The practical implementation of terahertz (THz) imaging and spectroscopic systems in real operational conditions requires them to be of a compact size, to have enhanced functionality, and to be user-friendly. This work demonstrates the single-sided integration of Fresnel-zone-plate-based optical elements with InGaAs bow-tie diodes directly on a semiconductor chip. Numerical simulations were conducted to optimize the Fresnel zone plate’s focal length and the InP substrate’s thickness to achieve constructive interference at 600 GHz, room-temperature operation and achieve a sensitivity more than an order of magnitude higher—up to 24.5 V/W—than that of a standalone bow-tie detector. Investigations revealed the strong angular dependence of the incident radiation on the Fresnel zone plate-integrated bow-tie diode’s response. These findings pave a promising avenue for the further development of single-sided integration of flat optics with THz detectors, enabling improved sensitivity, simplified manufacturing processes, and reduced costs for THz detection systems in a more compact design scheme. Full article
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Figure 1

Figure 1
<p>Sketch depicting the model of a bow-tie diode (BT) with an integrated Fresnel zone plate employed for the simulations. Left panel—schematic of the sensor with integrated Fresnel zone plate with incident plane THz wave. The rectangular parallelepiped around the model represents the modeling volume used in the simulations. Geometry of the model: <span class="html-italic">w</span> = 4000 μm, width; <span class="html-italic">d</span>—thickness of the substrate. The middle panel illustrates the THz wave propagation and focusing. The right panel shows the enlarged BT diode and its geometrical parameters: <span class="html-italic">b</span> = 5 μm, <span class="html-italic">L</span> = 100 μm, <span class="html-italic">W</span> = 25 μm, <span class="html-italic">I</span> = 40 μm, and <span class="html-italic">a</span> = 10 μm.</p>
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<p>Micrographs of the fabricated bow-tie detector with an integrated zone plate, designed for a 600 GHz frequency (BT + ZP), and the reference BT detector only with the contact pads. The left panel shows the entire structure, highlighting both the BT detector and the ZP elements. The center panel provides a zoomed view of the central part with a 200 μm scale bar and zone plate rings and contact pads. An enlarged image of the InGaAs BT detector’s active part and gold electrodes is shown in the right panel, with a 20 μm scale bar. Surface topographic cross-sections of the fabricated BT diode, depicted in the top-right corner, were measured along the length of the BT and across the BT using a DektakXT profilometer. Profile measurement lines are marked with dashed lines in the right panel. The measured profiles are shown in the insets.</p>
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<p>I–V characteristics of the BT detector with an integrated zone plate (BT + ZP; solid black line) and that without one (BT; solid orange line). Note the asymmetry of the I–V characteristics expressed via the asymmetry coefficient (<math display="inline"><semantics> <mrow> <mi>A</mi> <mo>=</mo> <mrow> <mo>(</mo> <msub> <mi>I</mi> <mi mathvariant="normal">F</mi> </msub> <mo>−</mo> <msub> <mi>I</mi> <mi mathvariant="normal">B</mi> </msub> <mo>)</mo> </mrow> <mo>/</mo> <mrow> <mo>(</mo> <msub> <mi>I</mi> <mi mathvariant="normal">F</mi> </msub> <mo>+</mo> <msub> <mi>I</mi> <mi mathvariant="normal">B</mi> </msub> <mo>)</mo> </mrow> </mrow> </semantics></math>), which is dependent on the applied voltage (dashed lines).</p>
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<p>A general view of the structure and the simulation results. Panel (<b>a</b>): Left picture—a single Fresnel zone plate. Note that the coverage of the backside of the substrate in gold is denoted in yellow. The central picture displays the distribution of the electric field strength in the <span class="html-italic">xy</span> plane. Right picture—enlarged part of the electric field’s distribution close to the sensors in the <span class="html-italic">yx</span> plane. Note the maximum interference in the vicinity of the sensor. Panel (<b>b</b>): a single BT diode (left picture) and the distribution of the electric field in the vicinity of the neck in the <span class="html-italic">xy</span> and <span class="html-italic">zx</span> planes (center top and bottom pictures, respectively). Simulations were performed on the surface of the substrate (<span class="html-italic">z</span> = 0 μm) for the single Fresnel zone plate and on the InP substrate in the case of the single BT diode (<span class="html-italic">z</span> = −0.5 μm). The dotted line represents the center of the simulated structure. The thickness of the InP substrate <span class="html-italic">d</span> = 335 μm; the focal length of the Fresnel zone plate <span class="html-italic">F</span> = 645 μm. Note the substantial increase in the electric field and its non-uniformity in the neck of the structure due to the asymmetrical design.</p>
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<p>General view of the structure and simulation results. Panel (<b>a</b>): Left picture—schematics of the BT diode and split zone contact pads. Right picture—distribution of the electric field strength in the <span class="html-italic">xy</span> plane (top part) and an enlarged cross-section in the <span class="html-italic">xz</span> plane (bottom part) in the active area of the BT diode placed on the InP substrate (<span class="html-italic">z</span> = −0.5 μm). The dotted lines represent the center of the simulated structure. Panel (<b>b</b>): Left picture—schematics of the BT diode, contact pads, and the Fresnel zone. Right picture—distribution of the electric field strength in the <span class="html-italic">xy</span> plane (top part) and an enlarged cross-section in the <span class="html-italic">xz</span> plane (bottom part) in the active area of the BT diode placed on the InP substrate (<span class="html-italic">z</span> = −0.5 μm). Note the strong increase in the electric field in the neck of the structure. Its triangle-like shape illustrates the non-uniformity of the electric field. The thickness of the InP substrate is <span class="html-italic">d</span> = 335 μm.</p>
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<p>Panel (<b>a</b>) represents the experimental setup and schematic connection used for focused beam imaging. The OAP denotes the off-axis parabolic mirrors. Panel (<b>b</b>) depicts the distribution of the intensity of the focused beam, registered when employing the on-chip integrated BT diode and the Fresnel ZP (top part) and the BT diode with contact pads only (bottom part). Left side—measurements along the optical axis in (<span class="html-italic">xz</span>), where the focal depth of the off-axis parabolic mirror with a 10 cm reflected focal length is scanned. Right side—measurements in the focal plane (<span class="html-italic">xy</span>). Red lines serve as a guide for the eyes to indicate focusing areas of the 3.9 μV signal, which is not strongly pronounced in the case with the standalone BT diode.</p>
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<p>Dependence of the detected signal of the structure on the incident angle. The gray line represents the BT diode with the integrated Fresnel ZP and the orange line that without it. The simulation results are given for comparison. The inset presents the setup and schematic connection used to measure the dependence of the signal on the incident angle of the THz radiation. The OAP denotes the off-axis parabolic mirrors.</p>
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27 pages, 4677 KiB  
Review
Weak Physycally Unclonable Functions in CMOS Technology: A Review
by Massimo Vatalaro, Raffaele De Rose, Marco Lanuzza and Felice Crupi
Chips 2025, 4(1), 3; https://doi.org/10.3390/chips4010003 - 30 Dec 2024
Viewed by 303
Abstract
Physically unclonable functions (PUFs) represent emerging cryptographic primitives that exploit the uncertainty of the CMOS manufacturing process as an entropy source for generating unique, random and stable keys. These devices can be potentially used in a wide variety of applications ranging from secret [...] Read more.
Physically unclonable functions (PUFs) represent emerging cryptographic primitives that exploit the uncertainty of the CMOS manufacturing process as an entropy source for generating unique, random and stable keys. These devices can be potentially used in a wide variety of applications ranging from secret key generation, anti-counterfeiting, and low-cost authentications to advanced protocols such as oblivious transfer and key exchange. Unfortunately, guaranteeing adequate PUF stability is still challenging, thus often requiring post-silicon stability enhancement techniques. The latter help to contrast the raw sensitivity to on-chip noise and variations in the environmental conditions (i.e., voltage and temperature variations), but their area and energy costs are not always feasible for IoT devices that operate with constrained budgets. This pushes the demand for ever more stable, area- and energy-efficient solutions at design time. This review aims to provide an overview of several weak PUF solutions implemented in CMOS technology, discussing their performance and suitability for being employed in security applications. Full article
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Figure 1

Figure 1
<p>Some of the most important Figures of Merit (FOMs) for PUFs.</p>
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<p>Some of the most relevant (<b>a</b>–<b>d</b>) mismatch-based, and (<b>e</b>,<b>f</b>) non mismatch-based PUF classes.</p>
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<p>Some of the most relevant delay-based solutions: (<b>a</b>) current-integrated differential NAND PUF [<a href="#B15-chips-04-00003" class="html-bibr">15</a>], (<b>b</b>) configurable RO solution proposed in [<a href="#B18-chips-04-00003" class="html-bibr">18</a>], and (<b>c</b>) thyristor-based solution proposed in [<a href="#B19-chips-04-00003" class="html-bibr">19</a>].</p>
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<p>Some of the most relevant SRAM-based solutions: (<b>a</b>–<b>c</b>) monostable-based cells proposed in [<a href="#B23-chips-04-00003" class="html-bibr">23</a>,<a href="#B24-chips-04-00003" class="html-bibr">24</a>,<a href="#B25-chips-04-00003" class="html-bibr">25</a>], (<b>d</b>) metastable-based 11T cell proposed in [<a href="#B31-chips-04-00003" class="html-bibr">31</a>], (<b>e</b>,<b>f</b>) delay-based cells proposed in (<b>e</b>) [<a href="#B32-chips-04-00003" class="html-bibr">32</a>] and (<b>f</b>) [<a href="#B33-chips-04-00003" class="html-bibr">33</a>].</p>
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<p>Some of the most relevant metastable-based bitcells: (<b>a</b>,<b>b</b>) cross-coupled comparators [<a href="#B35-chips-04-00003" class="html-bibr">35</a>,<a href="#B36-chips-04-00003" class="html-bibr">36</a>], (<b>c</b>) cross-coupled inverters proposed in [<a href="#B37-chips-04-00003" class="html-bibr">37</a>], and (<b>d</b>) cross-coupled NAND proposed in [<a href="#B39-chips-04-00003" class="html-bibr">39</a>], (<b>e</b>,<b>f</b>) transient effect ring oscillator (TERO) solutions [<a href="#B41-chips-04-00003" class="html-bibr">41</a>,<a href="#B42-chips-04-00003" class="html-bibr">42</a>].</p>
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<p>Some of the most relevant monostable-based bitcells based on (<b>a</b>) regulated cascode current mirrors [<a href="#B44-chips-04-00003" class="html-bibr">44</a>] (<b>b</b>) 2T amplifiers [<a href="#B49-chips-04-00003" class="html-bibr">49</a>], (<b>c</b>) subthreshold inverters [<a href="#B51-chips-04-00003" class="html-bibr">51</a>], (<b>d</b>) dual entropy [<a href="#B52-chips-04-00003" class="html-bibr">52</a>], (<b>e</b>) cross-coupled impedance [<a href="#B55-chips-04-00003" class="html-bibr">55</a>], and (<b>f</b>) cascode NAND gates [<a href="#B56-chips-04-00003" class="html-bibr">56</a>].</p>
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<p>(<b>a</b>) Conceptual diagram of the sub-threshold voltage divider-based PUF bitcell. (<b>b</b>) 2T- [<a href="#B58-chips-04-00003" class="html-bibr">58</a>], (<b>c</b>) 4T- [<a href="#B59-chips-04-00003" class="html-bibr">59</a>], (<b>d</b>) 6T-, (<b>e</b>) 8T-core based bitcell [<a href="#B60-chips-04-00003" class="html-bibr">60</a>].</p>
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<p>Some of the most relevant active PUF bitcells based on (<b>a</b>,<b>b</b>) hard oxide breakdown proposed in [<a href="#B61-chips-04-00003" class="html-bibr">61</a>,<a href="#B62-chips-04-00003" class="html-bibr">62</a>], respectively, (<b>c</b>) soft oxide breakdown proposed in [<a href="#B65-chips-04-00003" class="html-bibr">65</a>], and (<b>d</b>) quantum tunneling mechanism proposed in [<a href="#B66-chips-04-00003" class="html-bibr">66</a>].</p>
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<p>Some of the most relevant via PUF bitcells based on (<b>a</b>) contact formation probability [<a href="#B67-chips-04-00003" class="html-bibr">67</a>] and (<b>b</b>) metal via resistance [<a href="#B69-chips-04-00003" class="html-bibr">69</a>].</p>
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<p>Some of the most common PUF applications.</p>
Full article ">Figure 11
<p>Block diagram for (<b>a</b>) cryptographic key generation, (<b>b</b>) anti-counterfeiting, and (<b>c</b>) entity authentication.</p>
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<p>Comparison table among weak PUF solutions.</p>
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14 pages, 882 KiB  
Article
An 11-Bit Single-Slope/Successive Approximation Register Analog-to-Digital Converters with On-Chip Fine Step Range Calibration for CMOS Image Sensors
by Seong-Jun Byun, Jee-Taeck Seo, Tae-Hyun Kim, Jeong-Hun Lee, Young-Kyu Kim and Kwang-Hyun Baek
Electronics 2025, 14(1), 83; https://doi.org/10.3390/electronics14010083 - 27 Dec 2024
Viewed by 422
Abstract
This paper presents a novel high-precision 11-bit single-slope/successive approximation register analog-to-digital converter (SS/SAR ADC) architecture specifically designed for CMOS image sensors (CISs). The proposed design solves critical challenges in conventional ADCs by utilizing only two reference voltages, thereby minimizing voltage mismatch and completely [...] Read more.
This paper presents a novel high-precision 11-bit single-slope/successive approximation register analog-to-digital converter (SS/SAR ADC) architecture specifically designed for CMOS image sensors (CISs). The proposed design solves critical challenges in conventional ADCs by utilizing only two reference voltages, thereby minimizing voltage mismatch and completely eliminating the need for complex switch arrays. This unique approach reduces the transistor count by 64 per column ADC, significantly enhancing area efficiency and circuit simplicity. Furthermore, a groundbreaking on-chip fine step range calibration technique is introduced to mitigate the impact of parasitic capacitance, ensuring the precise alignment between coarse and fine steps and achieving exceptional linearity. Fabricated using a 0.18-µm CMOS process, the ADC demonstrates superior performance metrics, including a differential nonlinearity (DNL) of −1/+1.86 LSB, an integral nonlinearity (INL) of −2.74/+2.79 LSB, an effective number of bits (ENOB) of 8.3 bits, and a signal-to-noise and distortion ratio (SNDR) of 51.77 dB. Operating at 240 kS/s with a power consumption of 22.16 µW, the ADC achieves an outstanding figure-of-merit (FOMW) of 0.291 pJ/step. These results demonstrate the proposed architecture’s potential as a transformative solution for high-speed, energy-efficient CIS applications. Full article
(This article belongs to the Section Circuit and Signal Processing)
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<p>Previous SS/SAR ADC block diagram.</p>
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<p>Previous SS/SAR ADC timing diagram.</p>
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<p>Proposed SS/SAR ADC block diagram.</p>
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<p>Simplified schematic of the proposed SS/SAR ADC.</p>
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<p>(<b>a</b>) Pre-amplifier schematic and (<b>b</b>) StrongARM latch schematic.</p>
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<p>Ramp generator schematic.</p>
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<p>Unity–gain buffer schematic.</p>
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<p>(<b>a</b>) Proposed SS/SAR ADC timing diagram; (<b>b</b>) Comparator input waveform.</p>
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<p>(<b>a</b>) The degradation of the fine step range; and (<b>b</b>) Effects of the new reference voltage.</p>
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<p>Schematic of the CDAC with dummy capacitor array.</p>
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<p>Fine step range calibration timing diagram.</p>
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<p>Chip micrograph of the proposed design.</p>
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<p>Measured DNL and INL without calibration.</p>
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<p>Measured DNL and INL with calibration.</p>
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<p>Measured output spectrum without calibration.</p>
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<p>Measured output spectrum with calibration.</p>
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29 pages, 1433 KiB  
Article
Sparse Convolution FPGA Accelerator Based on Multi-Bank Hash Selection
by Jia Xu, Han Pu and Dong Wang
Micromachines 2025, 16(1), 22; https://doi.org/10.3390/mi16010022 - 27 Dec 2024
Viewed by 431
Abstract
Reconfigurable processor-based acceleration of deep convolutional neural network (DCNN) algorithms has emerged as a widely adopted technique, with particular attention on sparse neural network acceleration as an active research area. However, many computing devices that claim high computational power still struggle to execute [...] Read more.
Reconfigurable processor-based acceleration of deep convolutional neural network (DCNN) algorithms has emerged as a widely adopted technique, with particular attention on sparse neural network acceleration as an active research area. However, many computing devices that claim high computational power still struggle to execute neural network algorithms with optimal efficiency, low latency, and minimal power consumption. Consequently, there remains significant potential for further exploration into improving the efficiency, latency, and power consumption of neural network accelerators across diverse computational scenarios. This paper investigates three key techniques for hardware acceleration of sparse neural networks. The main contributions are as follows: (1) Most neural network inference tasks are typically executed on general-purpose computing devices, which often fail to deliver high energy efficiency and are not well-suited for accelerating sparse convolutional models. In this work, we propose a specialized computational circuit for the convolutional operations of sparse neural networks. This circuit is designed to detect and eliminate the computational effort associated with zero values in the sparse convolutional kernels, thereby enhancing energy efficiency. (2) The data access patterns in convolutional neural networks introduce significant pressure on the high-latency off-chip memory access process. Due to issues such as data discontinuity, the data reading unit often fails to fully exploit the available bandwidth during off-chip read and write operations. In this paper, we analyze bandwidth utilization in the context of convolutional accelerator data handling and propose a strategy to improve off-chip access efficiency. Specifically, we leverage a compiler optimization plugin developed for Vitis HLS, which automatically identifies and optimizes on-chip bandwidth utilization. (3) In coefficient-based accelerators, the synchronous operation of individual computational units can significantly hinder efficiency. Previous approaches have achieved asynchronous convolution by designing separate memory units for each computational unit; however, this method consumes a substantial amount of on-chip memory resources. To address this issue, we propose a shared feature map cache design for asynchronous convolution in the accelerators presented in this paper. This design resolves address access conflicts when multiple computational units concurrently access a set of caches by utilizing a hash-based address indexing algorithm. Moreover, the shared cache architecture reduces data redundancy and conserves on-chip resources. Using the optimized accelerator, we successfully executed ResNet50 inference on an Intel Arria 10 1150GX FPGA, achieving a throughput of 497 GOPS, or an equivalent computational power of 1579 GOPS, with a power consumption of only 22 watts. Full article
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<p>TPU architecture diagram, subfigure (<b>a</b>) illustrates the overall TPU architecture design. (<b>b</b>) illustrates the structure of the compute unit in each PE. [<a href="#B21-micromachines-16-00022" class="html-bibr">21</a>].</p>
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<p>Illustration of how sparse convolution is conducted.</p>
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<p>The overall architecture of proposed accelerator.</p>
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<p>Channel non-zero number(workload) in VGG16.</p>
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<p>Channel work balance over PE.</p>
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<p>Bank execute order intra PE.</p>
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<p>Prefetch window parallelism scheme.</p>
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<p>Intra channel array partitioning scheme.</p>
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<p>Synchronization scheme of parallel convolution tasks.</p>
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<p>Serialization of partial sum based on streaming.</p>
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<p>Sliding-window based fetching approach of Feature Map data.</p>
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<p>Multiple bank R/W design.</p>
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<p>Overall architecture of hash shared memory execution diagram.</p>
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<p>Data structure of stored weight file.</p>
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<p>Weight encoding scheme.</p>
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<p>Data format of quantization table.</p>
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<p>DSE of the shared memory bank selection.</p>
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<p>DSE of the design parameters. (<b>a</b>) shows the DSPs usage over <math display="inline"><semantics> <msub> <mi>N</mi> <mrow> <mi>i</mi> <mi>n</mi> </mrow> </msub> </semantics></math> after floorplanning. And the roofline limited by device is marked as dotted line. (<b>b</b>) shows the wall time of network reference over <math display="inline"><semantics> <msub> <mi>N</mi> <mrow> <mi>i</mi> <mi>n</mi> </mrow> </msub> </semantics></math>. The optimum design is marked in a red star. (<b>c</b>) shows the ALUTs usage with the increase of the parallel. and (<b>d</b>) shows the on-chip RAMs usage over <math display="inline"><semantics> <msub> <mi>N</mi> <mrow> <mi>i</mi> <mi>n</mi> </mrow> </msub> </semantics></math>, and the optimum design is found by the elimination of device resource, marked in red star.</p>
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<p>Efficiency of different kernel and Feature Map size.</p>
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<p>Comparision of the measured time, theoretic time, and efficiency.</p>
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<p>Roofline Model data point.</p>
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11 pages, 6207 KiB  
Article
A Generalized Design of On-Chip LTCC Balanced Filters Using Novel Hybrid Resonators with Intrinsic Ultra-Wideband Suppression for 5G Applications
by Wei Zhao, Yongle Wu, Zuoyu Xu and Weimin Wang
Electronics 2025, 14(1), 17; https://doi.org/10.3390/electronics14010017 - 24 Dec 2024
Viewed by 483
Abstract
In this paper, we examine an ultra-compact on-chip balanced filter based on novel hybrid resonators (NHRs) comprising short transmission line sections (STLSs) and series LC blocks using low-temperature co-fired ceramic (LTCC) technology. Based on a rigorous theoretical analysis, the proposed NHR demonstrates the [...] Read more.
In this paper, we examine an ultra-compact on-chip balanced filter based on novel hybrid resonators (NHRs) comprising short transmission line sections (STLSs) and series LC blocks using low-temperature co-fired ceramic (LTCC) technology. Based on a rigorous theoretical analysis, the proposed NHR demonstrates the potential for intrinsic ultra-wideband differential-mode (DM) and common-mode (CM) suppression without any additional suppressing structures. Furthermore, the resonance of NHRs was determined by four degrees of freedom, providing flexibility for miniaturization. Theoretical extensions of the Nth-order topology can be easily achieved by the simple coupling schemes that occur exclusively between STLSs. For verification, a balanced filter covering the 5G band n78 with an area of 0.065λg × 0.072λg was designed using the proposed optimization-based design procedure. An ultra-low insertion loss of 0.8 dB was obtained. The quasi-full CM stopband with a 20 dB rejection level ranged from 0 to 12.9 GHz. And the ultra-wide upper DM stopband with a 20 dB rejection level ranged from 4.4 to 11.5 GHz. Good agreement between the theoretical, simulated, and measured results indicate the validity of the proposed design principle. Full article
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<p>(<b>a</b>) Typical layout of the proposed LTCC-based balanced NHR, and (<b>b</b>) its schematic, DM circuit, and CM circuit.</p>
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<p>Three-dimensional mapping of the resonant frequency <math display="inline"><semantics> <msubsup> <mi>f</mi> <mn>0</mn> <mrow> <mi>dd</mi> </mrow> </msubsup> </semantics></math> against (<b>a</b>) the LC block [<span class="html-italic">C</span><sub>1</sub>, <span class="html-italic">L</span><sub>1</sub>] and (<b>b</b>) the STLS [<span class="html-italic">Z</span><sub>1</sub>, <span class="html-italic">θ</span>].</p>
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<p>(<b>a</b>) DM and (<b>b</b>) CM admittance curves versus frequency for NHRs (<span class="html-italic">C</span><sub>1</sub> = 1.5 pF and <span class="html-italic">L</span><sub>1</sub> = 0.65 nH).</p>
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<p>(<b>a</b>) Schematic of the proposed second-order balanced filter. Even-mode and odd-mode equivalent circuits under (<b>b</b>) DM and (<b>c</b>) CM excitation.</p>
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<p>(<b>a</b>) Different 3 dB FBW against variable <span class="html-italic">f</span><sub>TZ1</sub> (case I: <span class="html-italic">Z</span><sub>e</sub> = 148.7 Ω, <span class="html-italic">Z</span><sub>o</sub> = 72.8 Ω, case II: <span class="html-italic">Z</span><sub>e</sub> = 100.7 Ω, <span class="html-italic">Z</span><sub>o</sub> = 59.1 Ω, and case III: <span class="html-italic">Z</span><sub>e</sub> = 53 Ω, <span class="html-italic">Z</span><sub>o</sub> = 38.7 Ω). (<b>b</b>) Same 3 dB FBW against different STLS configurations.</p>
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<p>Ideal simulated results for the proposed prototype based on the initial and optimized parameters.</p>
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<p>Three-dimensional layout of the proposed LTCC balanced filter.</p>
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<p>Two-dimensional detail of the proposed LTCC balanced filter.</p>
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<p>(<b>a</b>) High-resolution photo of the fabricated filter chip. Theoretical, simulated, and measured (<b>b</b>) in-band S-parameters, (<b>c</b>) wideband DM responses, and (<b>d</b>) wideband CM responses (<span class="html-italic">L</span><sub>g1</sub> = 0.75 nH and <span class="html-italic">L</span><sub>g2</sub> = 0.35 nH).</p>
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<p>Measured and simulated (<b>a</b>) phase difference and (<b>b</b>) group delay.</p>
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<p>(<b>a</b>) <span class="html-italic">N</span>th-order topology, (<b>b</b>) <span class="html-italic">N</span>th-order circuit, and (<b>c</b>) fourth-order theoretical responses of the proposed balanced filter.</p>
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13 pages, 4857 KiB  
Article
High Performance GaSb-Based DBR Laser with On-Chip Integrated Power Amplifier via Gain-Match Design
by Juntian Cao, Chengao Yang, Yihang Chen, Hongguang Yu, Jianmei Shi, Haoran Wen, Zhengqi Geng, Zhiyuan Wang, Hao Tan, Yu Zhang, Donghai Wu, Yingqiang Xu, Haiqiao Ni and Zhichuan Niu
Appl. Sci. 2025, 15(1), 41; https://doi.org/10.3390/app15010041 - 24 Dec 2024
Viewed by 435
Abstract
We reported on a single-longitudinal-mode operated distributed Bragg reflector laser diode emitting at 1950 nm with an on-chip integrated power amplifier. Second-order Chromium–Bragg gratings are carefully designed and fabricated at the end of the ridge waveguide. Achieving a stable single-mode operation with a [...] Read more.
We reported on a single-longitudinal-mode operated distributed Bragg reflector laser diode emitting at 1950 nm with an on-chip integrated power amplifier. Second-order Chromium–Bragg gratings are carefully designed and fabricated at the end of the ridge waveguide. Achieving a stable single-mode operation with a large injecting current range of 800 mA from 15 °C to 40 °C. The maximum side-mode suppression ratio (SMSR) is up to 42 dB. To increase the output power, an on-chip integrated master oscillator power amplifier (MOPA) is also introduced. MOPA-DBR lasers with different matching configurations between the gain peak and Bragg wavelength are fabricated, resulting in various amplification consequences. The best device is realized with 40 nm red-shifted between Bragg wavelength and photoluminescence (PL) peak. A power amplification of 5.6 times is achieved with the maximum output power of 45 mW. Thus, we put up the feasibility and key design parameters of on-chip integrated power amplification DBR lasers towards mid-infrared. Full article
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<p>Schematic of the DBR laser and the optical field distribution of the fundamental mode.</p>
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<p>(<b>a</b>) κ as a function of the duty cycle Λ for the 2nd Cr grating. Reflectivity of DBR grating under (<b>b</b>) different coupling intensities and (<b>c</b>) absorption losses.</p>
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<p>(<b>a</b>) A diagram illustrating the layer stack of the epitaxial wafer. (<b>b</b>) X-ray diffraction patterns of the epitaxial wafer. (<b>c</b>) atomic force microscope image of the wafer surface and (<b>d</b>) The photoluminescence spectrum of the QW active layers measured at room temperature (25 °C).</p>
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<p>Top view of the DBR laser; detailed information on the grating is shown in the inset.</p>
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<p>Emission spectra of the DBR laser with a driving current from 1.3 A to 1.9 A at 25 °C. The inset shows the maximum SMSR with a driving current of 1.8 A at 25 °C.</p>
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<p>Emission spectra of lasers at different driving currents and temperatures.</p>
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<p>Wavelength tuning against current and the change of SMSR with current.</p>
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<p>Fundamental mode transmission angle corresponding to the width of ridge waveguide and wavelengths from 1.9 μm to 1.95 μm.</p>
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<p>Current–Voltage (<b>a</b>) and Power–Current (<b>b</b>) characteristics curves of MOPA lasers with different grating periods at room temperature.</p>
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<p>(<b>a</b>) Spectra of MOPA-DBR laser (#5) with period cycle of 537 nm. (<b>b</b>) The maximum output power, driving current range in single-mode operation, and the gain-peak drifting length of MOPA-DBR lasers (#4, #5, #6).</p>
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15 pages, 4064 KiB  
Article
Real-Time Monitoring Method and Circuit Based on Built-In Reliability Prediction
by Wenke Ren, Yanning Chen, Xiaoming Li, Xinjie Zhou, Baichen Song and Tianci Chang
Micromachines 2025, 16(1), 4; https://doi.org/10.3390/mi16010004 - 24 Dec 2024
Viewed by 369
Abstract
The failure of different chips under working conditions is influenced by various stress states such as different voltages, temperatures, stress durations, and stress variations. Therefore, the failure time has a great degree of dispersion, and similar chips may exhibit different failure mechanisms due [...] Read more.
The failure of different chips under working conditions is influenced by various stress states such as different voltages, temperatures, stress durations, and stress variations. Therefore, the failure time has a great degree of dispersion, and similar chips may exhibit different failure mechanisms due to variations in their working environments. This paper proposes three system-on-chip reliability failure prediction unit circuits: the time-dependent dielectric breakdown prediction circuit, the negative bias temperature instability prediction circuit, and the hot carrier injection prediction circuit. These circuits are embedded within the main chip, enabling real-time failure prediction and reliability mechanism diagnosis in the same working environment as the main chip. The three reliability failure prediction circuits are compact and energy efficient, allowing for their integration into a system on a chip as IP cores that provide early warning signals before system-on-chip failure. Compared to traditional reliability prediction methods, this approach offers the advantages of accurately identifying failure mechanisms, predicting failure times, and enabling real-time online monitoring. Full article
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<p>Reliability analysis methods for different design stages.</p>
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<p>Embedded on-chip real-time monitoring method.</p>
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<p>TDDB prediction circuit structure diagram; unit: μm.</p>
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<p>NBTI prediction circuit structure diagram; unit: μm.</p>
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<p>HCI prediction circuit structure diagram.</p>
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<p>Prediction circuit simulation timing diagram. (<b>a</b>) TDDB prediction circuit simulation timing diagram. (<b>b</b>) NBTI prediction circuit simulation timing diagram. (<b>c</b>) HCI prediction circuit simulation timing diagram.</p>
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<p>Test environment diagram. (<b>a</b>) TDDB prediction circuit test environment. (<b>b</b>) NBTI prediction circuit test environment. (<b>c</b>) HCI prediction circuit test environment.</p>
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<p>Test results of the prediction circuit. (<b>a</b>) TDDB prediction circuit test result. (<b>b</b>) NBTI prediction circuit test result. (<b>c</b>) HCI prediction circuit test result. (<b>d</b>) HCI prediction circuit’s output signals.</p>
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11 pages, 7800 KiB  
Communication
Lens-Free On-Chip Quantitative Phase Microscopy for Large Phase Objects Based on a Biplane Phase Retrieval Method
by Yufan Chen, Xuejuan Wu, Yang Chen, Wenhui Lin, Haojie Gu, Yuzhen Zhang and Chao Zuo
Sensors 2025, 25(1), 3; https://doi.org/10.3390/s25010003 - 24 Dec 2024
Viewed by 377
Abstract
Lens-free on-chip microscopy (LFOCM) is a powerful computational imaging technology that combines high-throughput capabilities with cost efficiency. However, in LFOCM, the phase recovered by iterative phase retrieval techniques is generally wrapped into the range of −π to π, necessitating phase unwrapping [...] Read more.
Lens-free on-chip microscopy (LFOCM) is a powerful computational imaging technology that combines high-throughput capabilities with cost efficiency. However, in LFOCM, the phase recovered by iterative phase retrieval techniques is generally wrapped into the range of −π to π, necessitating phase unwrapping to recover absolute phase distributions. Moreover, this unwrapping process is prone to errors, particularly in areas with large phase gradients or low spatial sampling, due to the absence of reliable initial guesses. To address these challenges, we propose a novel biplane phase retrieval (BPR) method that integrates phase unwrapping results obtained at different propagation distances to achieve accurate absolute phase reconstruction. The effectiveness of BPR is validated through live-cell imaging of HeLa cells, demonstrating improved quantitative phase imaging (QPI) accuracy when compared to conventional off-axis digital holographic microscopy. Furthermore, time-lapse imaging of COS-7 cells in vitro highlights the method’s robustness and capability for long-term quantitative analysis of large cell populations. Full article
(This article belongs to the Special Issue Digital Holography in Optics: Techniques and Applications)
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<p>The BPR of lens-free on-chip quantitative phase microscopy. (<b>a</b>) Schematic of the LFOCM system, including the CMOS sensor, color LED matrix, and sample. (<b>b</b>) Schematic comparison of BPR and traditional single-plane phase retrieval (PR) method under multi-wavelength illumination.</p>
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<p>Flowchart of the BPR algorithm, illustrating four stages: initialization of two planes, iterative phase retrieval, wavelength conversion and fusion, and multi-wavelength phase recovery.</p>
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<p>Experimental results of C166 cell slide. (<b>a1</b>,<b>b1</b>) The holograms of two selected regions. (<b>a2</b>,<b>b2</b>) Phase reconstruction of two regions under the CMW algorithm. (<b>a3</b>,<b>b3</b>) Zoomed-in comparison of the reconstructed phases of cell1 and cell2 using the CMW algorithm and the BPR algorithm. (<b>a4</b>,<b>a5</b>) and (<b>b4</b>,<b>b5</b>) Phase recovery of object plane 1 and object plane 2 in the selected region by the BPR algorithm. (<b>a6</b>,<b>b6</b>) Phase reconstruction of two regions under BPR algorithm. (<b>a7</b>,<b>b7</b>) Comparison of 3D rendering of cell1 and cell2 under CMW algorithm and BPR algorithm. (<b>a8</b>,<b>b8</b>) Phase values along the vertical line in (<b>a3</b>,<b>b3</b>).</p>
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<p>Experimental results of HeLa cells. (<b>a1</b>–<b>a3</b>) Phase reconstructed using DHM, CMW, and BPR methods. (<b>b1</b>–<b>b3</b>) Magnified regions of ROI 1. (<b>c1</b>–<b>c3</b>) Magnified regions of ROI 2. (<b>b4</b>,<b>c4</b>) Error maps between the BPR method and the DHM method in ROI 1 and ROI 2. (<b>d1</b>,<b>d2</b>) Phase value curves along the white solid line in ROI 1 and ROI 2. (<b>e</b>) A 3D rendering of the reconstructed phases by the DHM, CMW, and BPR methods.</p>
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<p>Dynamic phase imaging of COS-7 cells. (<b>a</b>) The hologram and phase reconstruction of the full FOV. (<b>b1</b>,<b>b2</b>) The 3D renderings corresponding to the cell in (<b>d1</b>,<b>d2</b>). (<b>c</b>) Cell dry mass computed under the BPR algorithm versus the CMW algorithm over time. (<b>d1</b>–<b>d6</b>,<b>e1</b>–<b>e6</b>) Six selected time-lapse phase images of ROI under the CMW algorithm and BPR algorithm. (<b>f1</b>–<b>f6</b>) Phase values along the white lines in (<b>d1</b>–<b>e6</b>).</p>
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14 pages, 4430 KiB  
Article
Development of Hemispherical 3D Models of Human Brain and B Cell Lymphomas Using On-Chip Cell Dome System
by Ryotaro Kazama, Rina Ishikawa and Shinji Sakai
Bioengineering 2024, 11(12), 1303; https://doi.org/10.3390/bioengineering11121303 - 23 Dec 2024
Viewed by 425
Abstract
Lymphocytes are generally non-adherent. This makes it challenging to fabricate three-dimensional (3D) structures mimicking the three-dimensional lymphoma microenvironment in vivo. This study presents the fabrication of a hemispherical 3D lymphoma model using the on-chip Cell Dome system with a hemispherical cavity (1 mm [...] Read more.
Lymphocytes are generally non-adherent. This makes it challenging to fabricate three-dimensional (3D) structures mimicking the three-dimensional lymphoma microenvironment in vivo. This study presents the fabrication of a hemispherical 3D lymphoma model using the on-chip Cell Dome system with a hemispherical cavity (1 mm in diameter and almost 300 µm in height). Both the human brain lymphoma cell line (TK) and human B cell lymphoma cell line (KML-1) proliferated and filled the cavities. Hypoxic regions were observed in the center of the hemispherical structures. CD19 expression did not change in either cell line, while CD20 expression was slightly upregulated in TK cells and downregulated in KML-1 cells cultured in the Cell Dome compared to those cultured in two-dimensional (2D) flasks. In addition, both TK and KML-1 cells in the hemispherical structures exhibited higher resistance to doxorubicin than those in 2D flasks. These results demonstrate the effectiveness of the on-chip Cell Dome for fabricating 3D lymphoma models and provide valuable insights into the study of lymphoma behavior and the development of new drugs for lymphoma treatment. Full article
(This article belongs to the Special Issue Advances on Cancer-on-Chip Models)
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<p>A schematic illustration of the Cell Dome preparation process. The process includes the preparation of the core gel with horseradish peroxidase (HRP), followed by the formation of the hydrogel shell with alg-Ph and gela-Ph through HRP-mediated hydrogelation, and finally, the immersion in the medium containing catalase for cell culture.</p>
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<p>A confocal microscope image of the Cell Dome fabricated using a mixture of alg-Ph and gela-Ph as the hydrogel shell material. The image shows the uniform hemispherical structure of the Cell Dome. The bar in the panel represents 500 µm.</p>
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<p>Microscopic images of TK (<b>a</b>) and KML-1 (<b>b</b>) cells cultured in the Cell Domes. (<b>c</b>) Histological section images of TK and KML-1 cells cultured in the Cell Domes for 10 days, showing the cell distribution within the cavities. (<b>d</b>) The absorbance values attributed to the mitochondrial activities of TK and KML-1 cells in the Cell Domes. The bars in panels (<b>a</b>–<b>c</b>) represent 250 µm. The bars in panel d represent the standard deviation (<span class="html-italic">n</span> = 3).</p>
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<p>Microscopic images of TK (<b>a</b>) and KML-1 (<b>b</b>) cells cultured in the high-density Cell Domes. (<b>c</b>) The absorbance values attributed to the mitochondrial activities of TK and KML-1 cells in the high-density Cell Domes. The bars in panels (<b>a</b>,<b>b</b>) represent 250 µm. The bars in panel (<b>c</b>) represent the standard deviation (<span class="html-italic">n</span> = 3).</p>
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<p>Fluorescence microscope images of TK (<b>a</b>) or KML-1 (<b>b</b>) cells cultured in the Cell Dome for 10 days and in a 2D flask, stained with hypoxia probe solutions. Red fluorescence indicates hypoxic conditions. (<b>c</b>) Fluorescence microscope images of TK or KML-1 cells cultured in the high-density Cell Domes for 3 days stained with hypoxia probe solutions. Red fluorescence indicates hypoxic conditions. (<b>d</b>) The relative gene expression of HIF-1α in TK or KMl-1 cells cultured for 10 days in the Cell Dome and cultured for 3 days in the high-density Cell Domes. The bars in panels (<b>a</b>–<b>c</b>) represent 250 µm. The bars in panel (<b>d</b>) represent the standard deviation (<span class="html-italic">n</span> ≥ 3, * <span class="html-italic">p</span> &lt; 0.05, n.s.: <span class="html-italic">p</span> &gt; 0.05).</p>
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<p>Flow cytometry analysis of CD19 and CD20 expression on 2D cultured TK or KMl-1 cells immunostained without anti-CD19 or anti-CD20 (negative control) and with anti-CD19 or anti-CD20 (positive control). (<b>a</b>) Cell Dome cultured cells for 2, 7, and 10 days immunostained with anti-CD19 or anti-CD20, and (<b>b</b>) high-density Cell Dome cultured cells for 3 days immunostained with anti-CD19 or anti-CD20.</p>
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<p>Viability of TK (<b>a</b>) or KML-1 (<b>b</b>) cells cultured in Cell Domes for 10 days, in high-density Cell Domes for 3 days, and in 2D flasks, with exposure to 10, 100, and 1000 nM doxorubicin (DOX). Bars represent standard deviation <span class="html-italic">(n</span> = 3, * <span class="html-italic">p</span> &lt; 0.05, n.s.: <span class="html-italic">p</span> &gt; 0.05).</p>
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16 pages, 1400 KiB  
Article
On-Chip Sensor Utilizing Concatenated Micro-Ring with Enhanced Temperature Invariance Using Deep Learning
by Thomas Mikhail, Sarah Shafaay and Mohamed Swillam
Photonics 2024, 11(12), 1198; https://doi.org/10.3390/photonics11121198 - 20 Dec 2024
Viewed by 373
Abstract
An approach to measuring chemical concentrations using a slotted micro-ring resonator (sMRR) is proposed which is robust to spectral shifts caused by temperature variations. Two 1-D Convolutional Neural Network architectures, ResNet34 and VGG20, were trained for regression, achieving mean squared errors (MSEs) of [...] Read more.
An approach to measuring chemical concentrations using a slotted micro-ring resonator (sMRR) is proposed which is robust to spectral shifts caused by temperature variations. Two 1-D Convolutional Neural Network architectures, ResNet34 and VGG20, were trained for regression, achieving mean squared errors (MSEs) of 1.1251 ×104 and 1.2195 ×104, respectively. The models predict concentrations of water, ethanol, methanol, and propanol (0–100%) from the transmission spectra of a single-ring sMRR etched in heavily doped silicon, operating in the mid-infrared range (290–310 K). Transfer learning adapted the models for datasets with different temperature ranges, analytes (e.g., butanol), and sMRR designs, achieving comparable accuracy. Variations in accuracy across these datasets are also explored. Full article
(This article belongs to the Section Lasers, Light Sources and Sensors)
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<p><b>Left</b> shows a ResNet Block, while <b>right</b> is a VGG block.</p>
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<p>Figures displaying geometry of sMRR with important parameters labeled. (<b>a</b>) Full ring resonator, (<b>b</b>) shows the electric field distribution <math display="inline"><semantics> <mrow> <mo>|</mo> <mi>E</mi> <mi>x</mi> <mo>|</mo> </mrow> </semantics></math> inside the simultaneous rings at 6.295 μm in air. The color bar indicates the normalized field magnitude, with red representing regions of maximum intensity and blue indicating regions of minimum intensity. (<b>c</b>) Cross-section of suspended slot waveguide. (<b>d</b>) Real <math display="inline"><semantics> <mrow> <mo>|</mo> <mi>H</mi> <mi>y</mi> <mo>|</mo> </mrow> </semantics></math> mode profile of slot.</p>
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<p>Sample effect of temperature on normalized transmission for the resonator used in this study.</p>
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<p>Effect of temperature on the (<b>a</b>) real and (<b>b</b>) imaginary permittivity of the doped silicon used in the study.</p>
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<p>Effect of temperature on (<b>a</b>) the general design for a concentric ring resonator. The waveguide is similar to that in <a href="#photonics-11-01198-f002" class="html-fig">Figure 2</a>b. (<b>b</b>) shows the electric field distribution <math display="inline"><semantics> <mrow> <mo>|</mo> <mi>E</mi> <mi>x</mi> <mo>|</mo> </mrow> </semantics></math> inside the simultaneous rings at 6.295 μm in air. The color bar indicates the normalized field magnitude, with red representing regions of maximum intensity and blue indicating regions of minimum intensity.</p>
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<p>Comparison of responses of ring designs under water.</p>
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<p>Losses in resonators of different radii, and proportion of types of losses at <math display="inline"><semantics> <mrow> <mi>λ</mi> <mo>=</mo> <mn>6</mn> </mrow> </semantics></math> μm.</p>
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<p>MSE loss during training for both models in training and validation datasets.</p>
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9 pages, 2760 KiB  
Article
Bandwidth-Tunable Optical Amplifier with Narrowband Filtering Function Enabled by Parity-Time Symmetry at Exceptional Points
by Kunpeng Zhu, Xiaoyan Zhou, Yinxin Zhang, Zhanhua Huang and Lin Zhang
Photonics 2024, 11(12), 1188; https://doi.org/10.3390/photonics11121188 - 19 Dec 2024
Viewed by 520
Abstract
Integrated optical amplifiers are the building blocks of on-chip photonic systems, and they are often accompanied by a narrowband filter to limit noise. In this sense, a bandwidth-tunable optical amplifier with narrowband filtering function is crucial for on-chip optical circuits and radio frequency [...] Read more.
Integrated optical amplifiers are the building blocks of on-chip photonic systems, and they are often accompanied by a narrowband filter to limit noise. In this sense, a bandwidth-tunable optical amplifier with narrowband filtering function is crucial for on-chip optical circuits and radio frequency systems. The intrinsic loss and coupling coefficients between resonator and waveguide inherently limit the bandwidth. The parity-time symmetric coupled microresonators operating at exceptional points enable near zero bandwidth. In this study, we propose a parity-time symmetric coupled microresonators system operating near EPs to achieve a bandwidth of 46.4 MHz, significantly narrower than bandwidth of 600.0 MHz and 743.2 MHz achieved by two all-pass resonators with identical gain/loss coefficients. This system also functions as an optical bandwidth-tunable filter. The bandwidth tuning ranges from 175.7 MHz to 7.8 MHz as gain coefficient adjusts from 0.2 dB/cm to 0.4 dB/cm. Our scheme presents a unique method to obtain narrow bandwidth from two broadband resonators and serves as an optical bandwidth-tunable filter, thereby paving a new avenue for exploring non-Hermitian light manipulation in all-optical integrated devices. Full article
(This article belongs to the Special Issue Group IV Photonics: Advances and Applications)
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<p>The schematics of coupled microresonators and all-pass resonators. The red and grey represent structures with gain and loss, respectively. (<b>a</b>) Description of coupled mode theory in time for coupled microresonators. (<b>b</b>) Description of TMM for coupled microresonators. (<b>c</b>) Description of TMM for an all-pass microresonator with gain. (<b>d</b>) Description of TMM for an all-pass microresonator with loss.</p>
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<p>Transmission and phase spectra of output field of through port. (<b>a</b>) Coupled resonator system operating at an EP with a shift to PT symmetry. (<b>b</b>) An all-pass microresonator with the same gain coefficient at the EP with a shift to PT symmetry. (<b>c</b>) An all-pass microresonator with the same loss coefficient at the EP with a shift to PT symmetry.</p>
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<p>Combinations of gain and loss coefficients range from 0.001 dB/cm to 10 dB/cm are scanned to get coupling coefficients meeting the EP condition. Every point represents a parameter set of an EP. Then the parameter sets are put into all-pass resonators to get the Q-factor. (<b>a</b>) Q-factors varying gain and loss. (<b>b</b>) <span class="html-italic">κ<sub>rr</sub></span> varying gain and loss. (<b>c</b>) <span class="html-italic">κ<sub>rb</sub></span> varying gain and loss.</p>
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<p>The bandwidth-tunable optical amplifier based on coupled microresonators. (<b>a</b>) FWHM and group delay varying gain coefficient near the EP. (<b>b</b>) Transmission and group delay spectra when gain coefficient is 0.11 dB/cm. (<b>c</b>) Transmission and group delay spectra when gain coefficient is 0.2 dB/cm. (<b>d</b>) FWHM and group delay when gain coefficient ranges from 0.1 dB/cm to 0.6 dB/cm. (<b>e</b>) Transmission and group delay spectra when gain coefficient is 0.4 dB/cm; (<b>f</b>) Transmission and group delay spectra when gain coefficient is 0.5 dB/cm.</p>
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<p>Transmission and phase spectra of coupled microresonators at different gain coefficients. (<b>a</b>) Gain coefficient is 0.11 dB/cm. (<b>b</b>) Gain coefficient is 0.2 dB/cm. (<b>c</b>) Gain coefficient is 0.4 dB/cm. (<b>d</b>) Gain coefficient is 0.5 dB/cm.</p>
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17 pages, 3787 KiB  
Article
Direct On-Chip Diagnostics of Streptococcus bovis/Streptococcus equinus Complex in Bovine Mastitis Using Bioinformatics-Driven Portable qPCR
by Jaewook Kim, Eiseul Kim, Seung-Min Yang, Si Hong Park and Hae-Yeong Kim
Biomolecules 2024, 14(12), 1624; https://doi.org/10.3390/biom14121624 - 18 Dec 2024
Viewed by 574
Abstract
This study introduces an innovative on-site diagnostic method for rapidly detecting the Streptococcus bovis/Streptococcus equinus complex (SBSEC), crucial for livestock health and food safety. Through a comprehensive genomic analysis of 206 genomes, this study identified genetic markers that improved classification and [...] Read more.
This study introduces an innovative on-site diagnostic method for rapidly detecting the Streptococcus bovis/Streptococcus equinus complex (SBSEC), crucial for livestock health and food safety. Through a comprehensive genomic analysis of 206 genomes, this study identified genetic markers that improved classification and addressed misclassifications, particularly in genomes labeled S. equinus and S. lutetiensis. These markers were integrated into a portable quantitative polymerase chain reaction (qPCR) that can detect SBSEC species with high sensitivity (down to 101 or 100 colony-forming units/mL). The portable system featuring a flat chip and compact equipment allows immediate diagnosis within 30 min. The diagnostic method was validated in field conditions directly from cattle udders, farm environments, and dairy products. Among the 100 samples, 51 tested positive for bacteria associated with mastitis. The performance of this portable qPCR was comparable to laboratory methods, offering a reliable alternative to whole-genome sequencing for early detection in clinical, agricultural, and environmental settings. Full article
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<p>Overview of the portable qPCR system and its components. (<b>A</b>) Portable qPCR device, illustrating the components and structure of the system. 1, LCD display; 2, heating plate; 3, groove for easy handling. (<b>B</b>) Microfluidic chip used for loading and processing samples in the qPCR device. (<b>C</b>) Thermal cycling temperature profiles of the portable qPCR system. (<b>D</b>) Real-time amplification screen of the portable qPCR system, displaying amplification progress in different channels. (<b>E</b>) Amplification curves generated by the portable qPCR system, representing the increase in fluorescence over cycles for different samples. (<b>F</b>) Melting curve analysis, showing the temperature-dependent dissociation of amplified products to assess specificity.</p>
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<p>Pangenome analysis of the SBSEC. (<b>A</b>) Phylogenetic tree and genome clustering. The circular phylogenetic tree displays the relationships between SBSEC strains based on whole-genome analysis. Each color in the outer ring represents different species within the complex. The tree branches indicate the evolutionary distance between the strains. The red squares in the outer ring highlight genomes that were misclassified. (<b>B</b>) The phylogenetic tree on the left shows the relationships among the 206 SBSEC strains, while the right panel displays a gene presence–absence matrix with 24,117 gene clusters. Each row corresponds to a strain and each column to a gene cluster, where dark blue indicates presence and light blue indicates absence. (<b>C</b>) This graph illustrates how the number of conserved genes declines as more genomes are analyzed, while the total number of genes continues to rise. (<b>D</b>) The plot shows that the number of new genes decreases steeply as additional genomes are added, but the count of unique genes stays nearly constant. (<b>E</b>) A pie chart categorizes the pangenome into core genes (99–100% of strains), soft-core genes (95–99%), shell genes (15–95%), and cloud genes (0–15%). The core genome contains 119 genes, the soft core has 222 genes, while the shell and cloud consist of 3772 and 20,004 genes, respectively.</p>
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<p>Specificity analysis of portable qPCR for SBSEC species detection. Amplification curves were generated for each target species. (<b>A</b>) <span class="html-italic">S. alactolyticus</span>, (<b>B</b>) <span class="html-italic">S. equinus</span>, (<b>C</b>) <span class="html-italic">S. gallolyticus</span> subsp. <span class="html-italic">gallolyticus</span>, (<b>D</b>) <span class="html-italic">S. gallolyticus</span> subsp. <span class="html-italic">macedonicus</span>, (<b>E</b>) <span class="html-italic">S. gallolyticus</span> subsp. <span class="html-italic">pasteurianus</span>, and (<b>F</b>) <span class="html-italic">S. lutetiensis</span> using species-specific primers. Each qPCR run was performed in triplicate, and the data represent mean values with error bars indicating standard deviations. The absence of amplification in nontarget (NT) and negative control (NC) samples demonstrates the high specificity of the portable qPCR assay for the target species.</p>
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<p>Limit of detection (LOD) for SBSEC using portable qPCR. (<b>A</b>) <span class="html-italic">S. alactolyticus</span>, (<b>B</b>) <span class="html-italic">S. equinus</span>, (<b>C</b>) <span class="html-italic">S. gallolyticus</span>, and (<b>D</b>) <span class="html-italic">S. lutetiensis</span> in pure culture. (<b>E</b>) <span class="html-italic">S. alactolyticus</span>, (<b>F</b>) <span class="html-italic">S. equinus</span>, (<b>G</b>) <span class="html-italic">S. gallolyticus</span>, and (<b>H</b>) <span class="html-italic">S. lutetiensis</span> in spiked food samples. Each bar represents qPCR signal intensity for serially diluted pure cultures, ranging from the highest concentration (left) to the lowest concentration (right), showing the sensitivity of detection for each species. The different bar colors represent the logarithmic CFU values (Log CFU per reaction) as indicated on the x-axis, with each color corresponding to a specific concentration step. All tests were conducted in triplicate, with standard deviation bars indicating variability between replicates.</p>
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<p>Standard curves for portable qPCR quantification of SBSEC species. Standard curves for SBSEC species detection using portable qPCR, showing the relationship between the logarithm of template concentration and Ct values. Each curve represents tenfold serial dilutions of DNA from the highest to lowest concentrations. (<b>A</b>) <span class="html-italic">S. alactolyticus</span>, (<b>B</b>) <span class="html-italic">S. equinus</span>, (<b>C</b>) <span class="html-italic">S. gallolyticus</span>, and (<b>D</b>) <span class="html-italic">S. lutetiensis</span> in pure culture. (<b>E</b>) <span class="html-italic">S. alactolyticus</span>, (<b>F</b>) <span class="html-italic">S. equinus</span>, (<b>G</b>) <span class="html-italic">S. gallolyticus</span>, and (<b>H</b>) <span class="html-italic">S. lutetiensis</span> in spiked food samples. All assays were performed in triplicate, with error bars representing the standard deviation of the replicates.</p>
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<p>Field diagnostic process of SBSEC using portable qPCR. (<b>A</b>) The farm where the samples were collected. (<b>B</b>) Swabbing of the udder surface for mastitis diagnosis. (<b>C</b>) Environmental sampling from the farm surroundings. (<b>D</b>) On-site diagnostic step performed immediately after sampling: 1, collected sample; 2, direct buffer for DNA extraction; 3, on-site diagnostic chip; 4, portable diagnostic device. (<b>E</b>) On-site DNA extraction performed immediately after sampling, taking less than 5 min at the farm site. (<b>F</b>) On-site analysis using the portable diagnostic device within 20 min.</p>
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