| 1. |
- Kumar, Tharagan, 1990-
(författare)
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The application of microfluidic devices and multifunctional fibers in cancer diagnostics
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Efficient separation and detection of rare cells in a mixed population is important in many biomedical applications. For instance, isolating and detecting circulating tumor cells (CTCs) from whole blood samples could allow for early cancer diagnosis and prognosis during treatment. CTCs are rare cells circulating in blood detached from the primary tumor site, carrying important information such as the origin of cancer and metastatic information. The detection of CTC from blood samples, besides being a minimally invasive procedure, could be vital in case of difficulty to access the tumor site via traditional biopsies, such as colon and pancreatic cancer. Microfluidics is a research field with great promise towards the development of methods to isolate and separate cells for clinical applications. Microfluidic based cell separation has been demonstrated using biological approaches using cell surface markers, and biophysical approaches using cell size, shape, and deformability. This thesis will focus on developing passive strategy using inertial microfluidics (biophysical, paper 1-4) and affinity biomarker (biochemical, paper 5) based strategy to isolate and analyze CTCs. Inertial microfluidics relies on inherent hydrodynamic forces, inertial forces, in flow through the microfluidic channel. Depending on the geometry of the channel, inertial forces drive the particles and cells to a specific streamline position, allowing for focusing and separation. In contrast, affinity-based isolation relies on biomarkers expressed on the surface of the targeted cells, which is highly specific. In paper 1, using the elasto inertial microfluidic technique, high throughput particle focusing and separation was achieved in a curved rectangular channel with a separation efficiency of 89% for 10 μm and 99% for the 15 μm particles at a high volumetric flow rate (1 mL/min). In paper 2, a detailed analysis of particle focusing was studied experimentally and numerically in a circular cross-section. Using the FENE-P model simulating non-Newtonian fluid and an immersed boundary method to account for the particles, it was observed that a combination of inertia and elasticity leads to several intermediate focusing positions. In paper 3, we developed a portable microflow cytometer using fiberoptics capillaries. By combining elasto inertial microfluidics and optical fibers, we focused particles and cells and demonstrated particle counting at a throughput of 2500 particles/second. In paper 4, we built an all-fiber separation and detection component and demonstrated a separation efficiency of 100% for the 10 μm and 97% for the 1 μm particles as a proof of principle. In addition, the separated 10 μm particles could beiiiquantified in the all-fiber component. In paper 5, an affinity-based separation approach was carried out to utilize the surface markers to capture and release viable CTCs for downstream analysis. A novel layer-by-layer nanofilm coating strategy was developed using cellulose nanofibril (CNF) built into multiple layers and functionalized with antibodies to capture the cells. After capture, the CNF were enzymatically degraded to release the CTCs. HCT116 colon cancer cells were captured with an efficiency of more than 97%, and when spiked in whole blood, an approximately 200 fold average enrichment was achieved compared to white blood cells. 80% of the cancer cells spiked in whole blood were recovered with 97% viability in less than 30 minutes.In summary, this thesis presents different microfluidics-based separation of cancer cells based on biophysical and biochemical properties. Using elasto inertial microfluidics, we developed several approaches to separate and detect cells and particles. Using layer-by-layer coating of CNF, we successfully demonstrated capture and release of cancer cells with maintained high viability. While the thesis has focused on different properties of cells for separation and analysis, combining these methods will be important for efficient isolation and characterization of CTCs for improved diagnostics.
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| 2. |
- Maniewski, Pawel
(författare)
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Additive manufacturing of fused silica glass
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Additive Manufacturing, of both metals and polymers, has seen rapid development in recent years, whereas the progress in glass has been rather slow. Today, glass can be considered the last frontier without a specialized 3D printing method available. Among different glass-like materials, silica glass is a high-performance material used in many parts of society. It is commonly associated with high mechanical, chemical, and thermal stability. The importance of 3D printing and additive manufacturing in the modern industry lies in the benefits and opportunities it facilitates. These include high flexibility in design and geometry, simplified production of customized objects, reduced material waste, and the ability to fabricate complex structures, often not possible when using traditional subtractive manufacturing.In this thesis, a novel method for additive manufacturing of silica glass is presented. Experiments and printed objects were madeusing the developed, experimental method. Here, by utilizinga method similar to the typical laser cladding, sintering of submicron silica powders was performed, and three-dimensional glass structures have been printed. Furthermore, by careful mixing of powders, a tailored composition of printed glass has been achieved. The high density and homogeneity of the printed parts made the developed method suitable for several different applications demonstrated in the last part of this thesis.The thesis describes the road from just an idea to the successful development of powder-based additive manufacturing of silica glass. The four papers in this compilation thesis show, first the setup development together with early-stage experiments (Paper I and II), and then there are two papers focused on early applications of the developed technology: one strictly mechanical (all-silica spotwelding, Paper III), and one optical (fiber prototyping, Paper IV).
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| 3. |
- Levenius, Martin, et al.
(författare)
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Spectral and angular mapping of parametric generation in purely nonlinear lattices
- 2012
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Ingår i: CLEO. - Washington, D.C. : Optical Society of America (OSA). ; , s. 6325882-
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Konferensbidrag (refereegranskat)abstract
- We investigate experimentally the spectral and angular degrees of freedom of multi-resonant optical parametric generation in hexagonally poled LiTaO3 and demonstrate access to twin-beam output for either signal or idler waves by pump angle tuning.
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| 4. |
- Mølster, Kjell Martin, 1992-
(författare)
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Backward and Forward Nonlinear Optical Processes in Potassium Titanyl Phosphate
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Second-order nonlinear optical processes generate radiation across a broad spectrum, including UV and the far-infrared. In this thesis, new light sources in the near(NIR) and mid infrared (MIR) using three-wave mixing geometries in periodically poled potassium titanyl phosphate (PPKTP) is studied.Collinear three-wave mixing is of three types: forward, counter, and backward, defined from propagation directions. Backward mixing is achievable with quasi-phasematching (QPM) - in contrast to birefringent phase matching which only can phasematch co- and counter- propagating geometries. Focus has been on optical parametric oscillators (OPOs), backward wave optical parametric oscillators (BWOPOs), and backward second harmonic generation (BSHG). OPO and BWOPO sources are attractive due to the need for stable, narrowband, and tunable MIR radiation in nanosecond stand-off spectroscopy. The work also pushes the boundaries of nonlinear optics, where lack of efficient sources has limited research on backward processes.Type-0 forward ns-OPOs have broad bandwidth, especially close to degeneracy, due to identical polarization at the parametric wavelengths and moderate dispersion. Probing greenhouse gases, such as CO2, requires narrow bandwidths. Type-2 ns-OPOs with orthogonal polarizations can be used as these have a much-reduced acceptance bandwidth. We provide the design parameters for the QPM grating periodicities in type-2 DFG, and, demonstrate that simple type-2 PPKTP ns-OPOs produce transform-limited mJ pulses with a good beam profile. These type-2 PPKTP OPOs can find use as parametric source for narrowband spectroscopy. Moreover, the type-2 OPOs are also useful for studying other narrow acceptance processes.We used BWOPOs to efficiently generate mJ of nanosecond pulses at 5 kHz repetition rate, corresponding to an average power of 5.65 W, with tunable forward pulses (1-to-1.001 Hz/Hz) and bandwidths ranging from 300 to 400 MHz. A BWOPO bandwidth as small as 274 MHz was obtained when pumped with a high M2 transform-limited laser. We show that the BWOPO is insensitive to temperature variations and is tuned at 2.48 GHz/K. The BWOPO can serve as a pump-tunable spectroscopy source using a single-pass crystal with reduced complexity.From the above, and earlier studies, PPKTP devices are found to be attractive as components for space-borne precision MIR spectroscopy. To study PPKTP's radiation hardness, we conducted experiments, using Type-0 OPO thresholds and transmission spectroscopy, on the long-term changes in linear and nonlinear properties of PPKTP when exposed to low- to mid-energy protons (10 and 60 MeV). The dosages and energies were similar to those in low earth orbit over a five-year period. The results showed no changes in nonlinearity or transmission.We also demonstrated the first efficient, purely backward χ(2) process, i.e., backward second-harmonic generation. The QPM period was Λ = 317 nm. The crystal generated frequency doubled pulses at 1154 nm with an efficiency of 18.7 % and energy of tens of microjoules. A narrowband type-2 ns-OPO was used as pump to measure the temperature bandwidth and confirm the quadratic output/input relationship in the undepleted pump regime. The significant difference in spectral acceptance between BSHG and second harmonic generation (SHG) in PPKTP - calculated to δλBSHG = 53 pm and δλSHG = 13.2 nm, respectively - is confirmed using a ps-BWOPO pump. The temperature tuning was 17.1 pm/K. This work establishes the feasibility of backward optical parametric amplification. We extended our research on potassium titanyl phosphate's (KTP) properties to the infrared and THz region by studying the transmission along the x and y crystallographic axis directions using THz pump-probe spectroscopy in reflection. Finally, backward THz polariton scattering was observed in Type-2 OPOs, along with polariton coupling into THz comb-lines when using an unpoled KTP as an off-axis oscillator.
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| 5. |
- Widarsson, Max, 1994-
(författare)
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Pulse Generation and Detection through Intra-Cavity Up-Conversion
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The work presented in this thesis concerns two main categories: pulse detection and pulse generation, however both utilise intra-cavity up-conversion. The work regarding pulse detection deals with up-conversion LIDAR and was split into two smaller projects, the first one focused on the resolution in measurements along one line with multiple reflections, and the second focused on measurements further into the MIR, as well as performing 3D imaging. The work on pulse generation was also split into two projects. In the first a solid-state laser was demonstrated that generated dark pulses, while the second project resulted in new way to achieve mode-locking and synchronously produced bright and dark pulses at two different wavelengths.The first LIDAR project utilised up-conversion detection 2.4 μm. The system had a temporal response of 42 ps (FWHM) and was able to detect two microscope slides separated by a few millimetres. In the second LIDAR project we pushed the LIDAR wavelength to slightly above 3 μm, and it was the longest wavelength that photon counting LIDAR had been performed at. The system could clearly resolve 1 mm deep features on a target and produce 3D images. Both the LIDAR systems used intra-cavity up-conversion with periodically poled rubidium doped KTiOPO4 (PPRKTP) in Nd:YVO4 lasers operating at 1064 nm.The dark pulse laser was based on sum-frequency generation (SFG) between a 1064 nm Nd:YVO4 laser and a mode-locked Yb-laser operating at 1040 nm. The mode-locked laser was focused into a PPRKTP placed inside the 1064 nm laser. By matching the cavity round-trip time of the 1064 nm laser to the repetition rate of the 1040 nm laser, the intensity dip produced by the SFG was enhanced for each round trip. The system could thereby produce dark pulses with a modulation depth of 90 % and a pulse width of 10 ps.In the last project bright pulses were produced by matching the cavity length of a 1064 nm Nd:YVO4 laser with that of a 1342 nm Nd:YVO4 laser. The two lasers formed a y-cavity, with a shared leg where a PPRKTP crystal was placed for phase-matched SFG between the two lasers. When the cavity lengths were matched, one laser produced bright mode-locked pulses and the other one dark pulses, synchronously. When the lasers enter this regime the SFG induced loss is significantly reduced due to the temporal overlap between the bright and dark pulse. The mode-locked pulses had a pulse width of 240 ps.
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| 6. |
- Barrett, Laura, et al.
(författare)
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High-contrast coercive field engineering for periodic poling of RbKTiOPO4 with Ba2+/K+ ion-exchange
- 2024
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Ingår i: Optics Express. - : Optica Publishing Group. - 1094-4087. ; 32:8, s. 14252-14260
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Tidskriftsartikel (refereegranskat)abstract
- We investigate a new method of coercive field engineering for periodic poling of RbKTiOPO4 (RKTP). By ion exchanging RKTP in a molten salt containing 7 mol% Ba(NO3)2 and 93 mol% KNO3 we achieve more than an order of magnitude difference in polarization switching time between the exchanged and non-exchanged regions. This method is used to fabricate periodic gratings of 2.92 µm in 1 mm thick bulk RKTP for second harmonic generation at 779 nm with a normalized conversion efficiency of 2%/Wcm. We show that the poled domain structures are stable at 300 °C, and that there is no bulk refractive index modification associated with the periodic ion exchange.
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| 7. |
- Barrett, Laura, et al.
(författare)
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Novel Coercive Field Engineering Method for Short Period KTiOPO4
- 2023
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Ingår i: 2023 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference, CLEO/Europe-EQEC 2023. - : Institute of Electrical and Electronics Engineers (IEEE).
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Konferensbidrag (refereegranskat)abstract
- The development of reliable periodic poling methods that allow for sub-µm quasi-phase matched (QPM) gratings and, at the same time, allow for waveguide implementation, is of paramount importance for a large number of applications. For instance, backward-wave optical parametric oscillators [1] are only viable if the QPM period is on the same order of magnitude as the wavelengths of the interacting waves. Furthermore, the integration of such QPM devices in a waveguide format would unveil countless possibilities in quantum optics employing the crystal as an ultrabright bi-photon source with unique spectral characteristics.
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| 8. |
- Brunzell, Martin, et al.
(författare)
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Free-Space Intra-Cavity Dark Pulse Generation
- 2021
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Ingår i: 2021 Conference On Lasers And Electro-Optics Europe & European Quantum Electronics Conference (CLEO/EUROPE-EQEC). - : Institute of Electrical and Electronics Engineers (IEEE).
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Konferensbidrag (refereegranskat)
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| 9. |
- Brunzell, Martin, et al.
(författare)
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Intra-cavity dark pulse generation through synchronized sum-frequency mixing
- 2022
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Ingår i: Optics Letters. - : Optica Publishing Group. - 0146-9592 .- 1539-4794. ; 47:5, s. 1105-1108
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Tidskriftsartikel (refereegranskat)abstract
- A Nd:YVO4 laser operating at 1064 nm generating a stable mode-locked train of 10 ps-long dark pulses with a 211 MHz repetition rate is presented. The mode-locking relies on a periodic loss modulation produced by intra-cavity sum-frequency mixing with a synchronous bright-pulse train from a mode-locked femtosecond Yb:KYW laser at 1040 nm. A modulation depth of 9050 was achieved for the dark pulses, confirmed by cross-correlation measurements. The ultrafast loss modulation injects power into the Nd:YVO4 laser cavity modes beyond the laser gain bandwidth. At proper laser cavity length, the detuning interaction of these modes with the lasing modes leads to the generation of periodic ultra-fast transients at frequencies above 1.5 THz.
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| 10. |
- Harish, Achar Vasant, et al.
(författare)
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Fiber Based Optofluidic Micro-Flow Cytometer Collecting Side-Scattered Light
- 2020
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Ingår i: Conference Proceedings - Lasers and Electro-Optics Society Annual Meeting-LEOS. - : Institute of Electrical and Electronics Engineers (IEEE).
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Konferensbidrag (refereegranskat)abstract
- A compact fiber capillary based microflow cytometer capable of detecting side-scattered-light is demonstrated by using a 45° angle-cleaved metal coated optical fiber tip.
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