BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the b...BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the bench side to routine clinical practice.In this study,we present a method that uses Raman spectroscopy(RS)to detect cancer in unstained formalin-fixed,resected specimens of the esophagus and stomach.Our method can record a clear Raman-scattered light spectrum in these specimens,confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue.AIM To evaluate the use of Raman-scattered light spectrum for detecting endoscopically resected specimens of esophageal squamous cell carcinoma(SCC)and gastric adenocarcinoma(AC).METHODS We created a Raman device that is suitable for observing living tissues,and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues.We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility,ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions.Furthermore,a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed.RESULTS We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens.After data capture,the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations.Based on data analysis of molecular-level substrates,we established cut-off values for the diagnosis of esophageal SCC and gastric AC.By analyzing specific Raman shifts,we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses.CONCLUSION Our technique provides qualitative information for real-time morphological diagnosis.However,further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.展开更多
BACKGROUND Colorectal cancer(CRC) is an important disease worldwide, accounting for the second highest number of cancer-related deaths and the third highest number of new cancer cases. The blood test is a simple and m...BACKGROUND Colorectal cancer(CRC) is an important disease worldwide, accounting for the second highest number of cancer-related deaths and the third highest number of new cancer cases. The blood test is a simple and minimally invasive diagnostic test. However, there is currently no blood test that can accurately diagnose CRC.AIM To develop a comprehensive, spontaneous, minimally invasive, label-free, bloodbased CRC screening technique based on Raman spectroscopy.METHODS We used Raman spectra recorded using 184 serum samples obtained from patients undergoing colonoscopies. Patients with malignant tumor histories as well as those with cancers in organs other than the large intestine were excluded. Consequently, the specific diseases of 184 patients were CRC(12), rectal neuroendocrine tumor(2), colorectal adenoma(68), colorectal hyperplastic polyp(18), and others(84). We used the 1064-nm wavelength laser for excitation. The power of the laser was set to 200 mW.RESULTS Use of the recorded Raman spectra as training data allowed the construction of a boosted tree CRC prediction model based on machine learning. Therefore, the generalized R^2 values for CRC, adenomas, hyperplastic polyps, and neuroendocrine tumors were 0.9982, 0.9630, 0.9962, and 0.9986, respectively.CONCLUSION For machine learning using Raman spectral data, a highly accurate CRC prediction model with a high R^2 value was constructed. We are currently planning studies to demonstrate the accuracy of this model with a large amount of additional data.展开更多
We investigated single damascene integration with Porous MSQ (Methyl-Silsesqui-oxane, k value is 2.3) and Spin on Low k MSQ (k value is 2.9) as hard mask on Porous MSQ. Mechanical property of Low k material is improve...We investigated single damascene integration with Porous MSQ (Methyl-Silsesqui-oxane, k value is 2.3) and Spin on Low k MSQ (k value is 2.9) as hard mask on Porous MSQ. Mechanical property of Low k material is improved by Electron Beam (EB) Cure technology. And also One time cure of stacked Low k is successful without any problem. On integration issue of Low k material, we demonstrated low damage resist strip process by using reducing gas chemistry and clarified mechanism of new Cu corrosion mode during CMP process.展开更多
Thera no stic nano particles are integrated systems useful for simulta neous diag nosis and imaging guided delivery of therapeutic drugs, with wide ranging pote ntial applicati ons in the clinic. Here we developed a t...Thera no stic nano particles are integrated systems useful for simulta neous diag nosis and imaging guided delivery of therapeutic drugs, with wide ranging pote ntial applicati ons in the clinic. Here we developed a thera no stic nan oparticle (~24 nm size by dynamic light scatteri ng) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1,000-1,700 nm second near-infrared (NIR-Ⅱ) window and an an ti-ca ncer drug paclitaxel. Folic acid (FA) was conjugated to the nan oparticles to afford specific binding to molecular folate receptors on muri ne breast can cer 4T1 tumor cells. In vivo, the nan oparticles accumulated in 4T1 tumor through both passive and active targeting effect. Under an 808 nm laser excitation, fluorescence detection above 1,300 nm afforded a large Stokes shift, allowing targeted molecular imaging tumor with high signal to background ratios, reaching a high tumor to normal tissue signal ratio (T/NT) of (20.0±2.3). Further, 4T1 tumors on mice were completed eradicated by paclitaxel released from p-FE-PTA-FA within 20 days of the first injection. Pharmacokinetics and histology studies indicated p-FE-PTX-FA had no obvious toxic side effects to major organs. This represented the first NIR-Ⅱ theranostic age nt developed.展开更多
A quantum chemistry study of the first singlet(S_(1))and triplet(T_(1))excited states of phenylsulfonyl-carbazole compounds,proposed as useful thermally activated delayed fluorescence(TADF)emitters for organic light e...A quantum chemistry study of the first singlet(S_(1))and triplet(T_(1))excited states of phenylsulfonyl-carbazole compounds,proposed as useful thermally activated delayed fluorescence(TADF)emitters for organic light emitting diode(OLED)applications,was performed with the quantum Equation-Of-Motion Variational Quantum Eigensolver(qEOM-VQE)and Variational Quantum Deflation(VQD)algorithms on quantum simulators and devices.These quantum simulations were performed with double zeta quality basis sets on an active space comprising the highest occupied and lowest unoccupied molecular orbitals(HOMO,LUMO)of the TADF molecules.The differences in energy separations between S_(1) and T_(1)(ΔEST)predicted by calculations on quantum simulators were found to be in excellent agreement with experimental data.Differences of 17 and 88 mHa with respect to exact energies were found for excited states by using the qEOM-VQE and VQD algorithms,respectively,to perform simulations on quantum devices without error mitigation.By utilizing state tomography to purify the quantum states and correct energy values,the large errors found for unmitigated results could be improved to differences of,at most,4 mHa with respect to exact values.Consequently,excellent agreement could be found between values ofΔEST predicted by quantum simulations and those found in experiments.展开更多
基金Supported by MEXT KAKENHI,JP17K09022 and JP20K07643.
文摘BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the bench side to routine clinical practice.In this study,we present a method that uses Raman spectroscopy(RS)to detect cancer in unstained formalin-fixed,resected specimens of the esophagus and stomach.Our method can record a clear Raman-scattered light spectrum in these specimens,confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue.AIM To evaluate the use of Raman-scattered light spectrum for detecting endoscopically resected specimens of esophageal squamous cell carcinoma(SCC)and gastric adenocarcinoma(AC).METHODS We created a Raman device that is suitable for observing living tissues,and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues.We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility,ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions.Furthermore,a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed.RESULTS We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens.After data capture,the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations.Based on data analysis of molecular-level substrates,we established cut-off values for the diagnosis of esophageal SCC and gastric AC.By analyzing specific Raman shifts,we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses.CONCLUSION Our technique provides qualitative information for real-time morphological diagnosis.However,further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.
基金the Japanese Society for the Promotion of Science (JSPS),based on the JSPS KAKENHI Grants-in-Aid for Scientific Research (C),No. JP17K09022。
文摘BACKGROUND Colorectal cancer(CRC) is an important disease worldwide, accounting for the second highest number of cancer-related deaths and the third highest number of new cancer cases. The blood test is a simple and minimally invasive diagnostic test. However, there is currently no blood test that can accurately diagnose CRC.AIM To develop a comprehensive, spontaneous, minimally invasive, label-free, bloodbased CRC screening technique based on Raman spectroscopy.METHODS We used Raman spectra recorded using 184 serum samples obtained from patients undergoing colonoscopies. Patients with malignant tumor histories as well as those with cancers in organs other than the large intestine were excluded. Consequently, the specific diseases of 184 patients were CRC(12), rectal neuroendocrine tumor(2), colorectal adenoma(68), colorectal hyperplastic polyp(18), and others(84). We used the 1064-nm wavelength laser for excitation. The power of the laser was set to 200 mW.RESULTS Use of the recorded Raman spectra as training data allowed the construction of a boosted tree CRC prediction model based on machine learning. Therefore, the generalized R^2 values for CRC, adenomas, hyperplastic polyps, and neuroendocrine tumors were 0.9982, 0.9630, 0.9962, and 0.9986, respectively.CONCLUSION For machine learning using Raman spectral data, a highly accurate CRC prediction model with a high R^2 value was constructed. We are currently planning studies to demonstrate the accuracy of this model with a large amount of additional data.
文摘We investigated single damascene integration with Porous MSQ (Methyl-Silsesqui-oxane, k value is 2.3) and Spin on Low k MSQ (k value is 2.9) as hard mask on Porous MSQ. Mechanical property of Low k material is improved by Electron Beam (EB) Cure technology. And also One time cure of stacked Low k is successful without any problem. On integration issue of Low k material, we demonstrated low damage resist strip process by using reducing gas chemistry and clarified mechanism of new Cu corrosion mode during CMP process.
文摘Thera no stic nano particles are integrated systems useful for simulta neous diag nosis and imaging guided delivery of therapeutic drugs, with wide ranging pote ntial applicati ons in the clinic. Here we developed a thera no stic nan oparticle (~24 nm size by dynamic light scatteri ng) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1,000-1,700 nm second near-infrared (NIR-Ⅱ) window and an an ti-ca ncer drug paclitaxel. Folic acid (FA) was conjugated to the nan oparticles to afford specific binding to molecular folate receptors on muri ne breast can cer 4T1 tumor cells. In vivo, the nan oparticles accumulated in 4T1 tumor through both passive and active targeting effect. Under an 808 nm laser excitation, fluorescence detection above 1,300 nm afforded a large Stokes shift, allowing targeted molecular imaging tumor with high signal to background ratios, reaching a high tumor to normal tissue signal ratio (T/NT) of (20.0±2.3). Further, 4T1 tumors on mice were completed eradicated by paclitaxel released from p-FE-PTA-FA within 20 days of the first injection. Pharmacokinetics and histology studies indicated p-FE-PTX-FA had no obvious toxic side effects to major organs. This represented the first NIR-Ⅱ theranostic age nt developed.
基金Q.G.,M.S.,H.C.W.,E.W.,Y.O.,H.N.and N.Y.acknowledge support from MEXT Quantum Leap Flagship Program Grant Number JP-MXS0118067285 and JP-MXS0120319794。
文摘A quantum chemistry study of the first singlet(S_(1))and triplet(T_(1))excited states of phenylsulfonyl-carbazole compounds,proposed as useful thermally activated delayed fluorescence(TADF)emitters for organic light emitting diode(OLED)applications,was performed with the quantum Equation-Of-Motion Variational Quantum Eigensolver(qEOM-VQE)and Variational Quantum Deflation(VQD)algorithms on quantum simulators and devices.These quantum simulations were performed with double zeta quality basis sets on an active space comprising the highest occupied and lowest unoccupied molecular orbitals(HOMO,LUMO)of the TADF molecules.The differences in energy separations between S_(1) and T_(1)(ΔEST)predicted by calculations on quantum simulators were found to be in excellent agreement with experimental data.Differences of 17 and 88 mHa with respect to exact energies were found for excited states by using the qEOM-VQE and VQD algorithms,respectively,to perform simulations on quantum devices without error mitigation.By utilizing state tomography to purify the quantum states and correct energy values,the large errors found for unmitigated results could be improved to differences of,at most,4 mHa with respect to exact values.Consequently,excellent agreement could be found between values ofΔEST predicted by quantum simulations and those found in experiments.
