Molecular Diagnosis of Human Papillomavirus Infection in Uterine Cervix

학위논문 (석사)-- 서울대학교 대학원 : 의학과, 2012. 2. 박성섭.자궁경부암은 여성 암 중에서 발병율 6위에 해당하는 주요 암으로, 자궁경부의 인유두종 바이러스의 지속적인 감염이 원인이다. 자궁경부암 선별검사에서 암을 유발할 가능성이 높은 고위험군 인유두종 바이러스 검사는 자궁경부암 또는 전암 병변을 조기에 진단하는데 중요한 과정이 되었다. 고위험군 인유두종 바이러스의 검사법 중에서 국내에서 보편적으로 사용되는 Hybrid Capture II, HPV DNA Chip 검사법과 새롭게 개발된 RealTime High-risk HPV검사법에 대해 임상적 유용성과 정확도를 평가하고 분석하였다. 2009년 12월 30일부터 2010년 9월 15일까지 서울대병원 진단검사의학과에 Hybrid Capture II 검사를 의뢰한 환자787명과 HPV DNA chip 검사를 의뢰한 환자 204명을 대상으로 각각의 검사와 함께 RealTime High-risk HPV 검사와 중합효소연쇄반응 및 직접염기서열 검사를 시행하여 유전형을 분석하였다. 검출 한계 평가는 CaSki cell-line과 HeLa cell-line을 사용하였고, 환자의 자궁경부 세포진 검사 결과와 생검 검사 결과는 의무기록을 조회하여 조사하였다. 자궁경부 세포진 검사 결과를 정상과 비정상 환자군으로 구분하여 분석했을 때 Hybrid Capture II의 임상민감도는 72.9%, RealTime High-risk HPV는 62.9%, HPV DNA Chip은 68.2% 였고, 경증과 중증 환자군으로 구분하여 분석했을 때 Hybrid Capture II의 임상민감도는 77.3%, RealTime High-risk HPV는 81.8%, HPV DNA Chip은 66.7%였다. 자궁경부 생검 검사 결과를 정상과 비정상 환자군으로 구분하여 분석했을 때 Hybrid Capture II의 임상민감도는 81.8%, RealTime High-risk HPV는 75.0%, HPV DNA Chip은 61.5% 였고, 경증과 중증 환자군으로 구분하여 분석했을 때 Hybrid Capture II의 임상민감도는 91.7%, RealTime High-risk HPV는 87.5%, HPV DNA Chip은 73.3%였다. PGMY primer를 이용한 중합효소연쇄반응 및 직접염기서열 검사로 분석한 결과 고위험군 인유두종 바이러스 검출에 대한 분석민감도는 Hybrid Capture II는 91.9%, %, RealTime High-risk HPV는 87.8%, HPV DNA Chip은 71.4%였다. 직접염기서열 검사로 밝힌 HPV 유전형과 HPV DNA Chip의 유전형 결과에서 일치율은 57.1%였다. RealTime High-risk HPV는 양성 기준이 되는 cycle threshold를 32 cycle에서 38 cycle로 변경했을 때 임상민감도와 분석민감도가 향상되어 Hybrid Capture II에 준하는 결과를 보였다. Hybrid Capture II는 임상민감도와 분석민감도에서 전체적으로 고른 결과를 보이며 우수한 성능을 보였다. 그러나 내부 대조군을 포함하고 있지 않아 검체의 적절성을 평가할 수 없었다. HPV DNA Chip은 임상민감도와 분석민감도가 가장 낮았으며, 유전형의 정확도가 낮아 개선이 필요한 것으로 판단된다. RealTime High-risk HPV는 임상민감도와 분석민감도가 우수하였고 내부 대조군을 포함하고 있으며, 감염 빈도가 높고 발암성이 높은 인유두종 바이러스 16과 18 유전형을 구분하여 검출할 수 있는 장점이 있어 기존의 인유두종 바이러스 검사를 대체할 수 있을 것으로 기대된다.Cervical cancer, as the sixth common cancer in Korean women, is mainly caused by persistent Human papillomavirus (HPV) infection in uterine cervix. The high-risk HPV test in cervical cancer screening has become important for early diagnosis of cervical cancer or pre-cancerous lesion, which indicates a higher probability of cervical cancer. Among high-risk HPV tests, Hybrid Capture II and HPV DNA Chip tests, which are widely used in Korea, as well as newly developed RealTime High-risk HPV test, were evaluated and analyzed in clinical and analytical performance. With the subjects of 787 patients, who requested a Hybrid Capture II test, and 204 who requested a HPV DNA chip test, Between Dec 30, 2009 and Sep 15, 2010, to the Department of Laboratory Medicine, RealTime High-risk HPV test and genotype analysis were performed, as well as the relevant test for them each. For an evaluation of limit of detection, CaSki cell-line and HeLa cell-line were applied. Medical informations for cervical cytologic and histologic examination were collected with reviewing of their electronic medical records. According to analysis of cervical cytology for the normal and the abnormal patient groups each, the Hybrid Capture II test showed 72.9% of clinical sensitivity, the RealTime High-risk HPV test, 62.9% and the HPV DNA Chip test, 68.2%. For the normal or mild, and the severe patient groups each, the Hybrid Capture II test showed 77.3% of clinical sensitivity, the RealTime High-risk HPV test, 81.8%, and the HPV DNA Chip test, 66.7%. In cervical histology for the normal and the abnormal patient groups each, the Hybrid Capture II showed 81.8% of clinical sensitivity, the RealTime High-risk HPV test, 75.0%, and the HPV DNA Chip test, 61.5%, For the normal or mild, and the severe histology patient groups each, the Hybrid Capture II showed 91.7% of clinical sensitivity, the RealTime High-risk HPV test, 87.5%, and the HPV DNA Chip test, 73.3%. According to analysis of the conventional PCR and direct sequencing using PGMY primer, the Hybrid Capture II test showed 91.9% of analytical sensitivity for high-risk HPV detection, the RealTime High-risk HPV test, 87.8%, and the HPV DNA Chip test, 71.4%. The concurrence rate between HPV genotyping results from direct sequencing and genotyping results from the HPV DNA Chip test was 57.1%. The RealTime High-risk HPV showed an increase in clinical and analytical sensitivity, which corresponded to the Hybrid Capture II test, when the cycle threshold considered positive was adjusted from 32 to 38 cycles. The Hybrid Capture II test showed regular and excellent efficiency in clinical and analytical sensitivity on the whole. However, the improvement is needed, in view of inadequacy of evaluation of the relevance of specimen without internal control. The HPV DNA Chip test showed the lowest clinical and analytical sensitivity, and low genotyping accuracy, so its improvement is needed. The RealTime High-risk HPV test showed excellent clinical and analytical sensitivity and included internal control, as well as separate detection of HPV 16 and 18 with higher infection frequency and carcinogenicity. Accordingly, it is expected to be replaced with the conventional HPV test.Maste

Technological History of Laparoscopy: Transfer, Spread, and Influence of Laparoscopy in 1970–80s South Korea

This paper analyzes the transfer and spread of laparoscopy in Korea in the 1970–80s and its impact on Korean society from a historical perspective. It raises three questions: first, what was the reason that laparoscopy was introduced and spread in Korea, even though other contraceptive technologies were already in use? Second, what was the impact of laparoscopy on the Family Planning Program in Korea? Third, what subsequent effect did laparoscopy have on obstetricians in Korea? To clarify these points, this study examines government documents, NGO reports, and medical research papers produced in Korea and the United States of America (USA). There were three main reasons due to which laparoscopy was introduced and spread in Korea. Firstly, it was the necessity and the possibility of new contraceptive technology. The limitations of existing contraceptive technology led to the need for tubal sterilization. Intrauterine devices and oral contraceptives caused many side effects due to defects in the technology itself and baseless target amount; additionally, they were a substantial economic burden due to their long-term costs. Vasectomy and artificial abortion were suggested as alternatives, but the limitations were obvious; vasectomy could not overcome the psychological resistance among males, while artificial abortion was vulnerable to the ethical condemnation of sacrificing life. As intrauterine devices, oral contraceptives, vasectomy, and artificial abortion exposed several limitations, tubal sterilization, which had not been discussed as an alternative, began to emerge as a viable method. The Hospital Family Planning Program and the introduction of laparoscopy realized and expanded the possibilities of tubal sterilization, which until the early 1970s had been a difficult surgery, only available at hospital-level institutions. This constraint was resolved with the implementation of the Hospital Family Planning Program in response to the rise of the urban population problem. As hospitals, concentrated in cities, emerged as new centers of family planning, the technological limitations blocking the spread of tubal sterilization were naturally solved; further, laparoscopic surgery, introduced in the mid-1970s, expanded possibilities of tubal sterilization. With the introduction of laparoscopy, tubal sterilization changed from a complicated surgery requiring hospital-level institutions to a simple surgery available at clinic-level institutions. With both necessity and possibility in place, tubal sterilization became a key means of the Family Planning Program. The second reason is that laparoscopy met the interests of the governments and medical professionals of both the USA and Korea. In the late 1960s, the governments of both countries sought new means to replace the existing contraceptive technologies. As mentioned above, intrauterine devices and oral contraceptives caused frequent side effects and were quite expensive. Under these circumstances, laparoscopy emerged as a groundbreaking technology for popularizing tubal sterilization, decreasing the difficulty of the operation and increasing its safety. Although the problem of its high initial cost remained, a single surgery could have a permanent contraceptive effect, thus, it seemed to be an economical option. For both governments, laparoscopy was an excellent technical solution to overcome the technological and economic limitations of existing contraceptive technologies. Laparoscopy also met the interests of medical practitioners in both countries. Obstetricians in developed countries, leading the development and diffusion of contraceptive technology, were able to secure huge amounts of clinical cases through worldwide population control projects. Proving the effectiveness of new medical technologies required a sufficient number of cases; however, this was not an easy task in developed countries, where population problems were not prominent. The solution was the ‘extension of the operating room.’ If the surgical procedure could be standardized and the results could be reported in a systemized format, cases could be collected easily from various countries. Medical professionals in Korea also saw their benefits. Based on the network between Korea and the USA through the standardization of laparoscopic surgery, obstetricians in the former country received technology transfer and exerted authority as experienced surgeons. Behind the Johns Hopkins Program for International Education in Gynecology and Obstetrics lay the overlapping interests of the governments and medical professionals of both countries. Lastly, laparoscopy was technically improved to suit the situation of developing countries. When first used for tubal sterilization, laparoscopy was not an appropriate technique to be used in developing countries as it was neither safe nor cheap. Laparoscopic surgeries sometimes caused complications, such as perforation of the small intestine; furthermore, in developing countries, where medical personnel and facilities were scarce, such complications could threaten the lives of the patients. The lack of safety was a major flaw preventing the spread of laparoscopic sterilization, as it could not be implemented at the expense of people’s lives. The complexity and low economic efficiency of laparoscopy were also problematic. Although it was simple and inexpensive compared to open surgery, it was still complex and too expensive to be widely used in developing countries. To solve these problems, public and private organizations such as the United States Agency for International Development and the Ford Foundation, and several medical professionals dove into the improvement of laparoscopy; consequently, laparoscopy became affordable and safe enough for developing countries. With three conditions in place, the necessity and the possibility for tubal sterilization, overlapping of the interests in technology transfer, and technological improvement to suit the environment of the developing countries, laparoscopy could be transferred and spread rapidly. After laparoscopy was introduced in Korea, laparoscopic tubal sterilization quickly matched other contraceptive techniques and finally outpaced them in the early 1980s. The second and third questions correspond to the influence of laparoscopy on Korean society. Regarding the impact on the Family Planning Program, laparoscopy solidified and deepened the male-dominant gender order. The Family Planning Program had always targeted women. It was the result of the consensus of the two major powers, namely, government officials and doctors; most government officials viewed family planning as the job of a ‘housewife,’ and doctors also focused mostly on female contraception. It is no exaggeration to state that the Family Planning Program was a project to spread female contraceptive technologies. The budget was focused on the dissemination of intrauterine devices and oral contraceptives rather than vasectomy; in turn, it became evidence proving the effectiveness of targeting women, fixing them the subject of the program. Laparoscopy consolidated this flow. The side effects of intrauterine devices and oral contraceptives, ironically, could resolve gender inequality in family planning strategies. As the sustainability of the program became uncertain, a group of bureaucrats and doctors who had shifted all responsibility to women began to reorient the plan toward vasectomy. With the introduction of laparoscopy, however, the plan focused on women again. As laparoscopy popularized tubal sterilization, political will toward vasectomy decreased accordingly. In the circular logic by which the availability of technology determined the direction of the policy, and such policy proved the value of technology, women became the set target of the Family Planning Program, and laparoscopy became a driving force to maintain this vicious circle. The same was true for the initiative of the Family Planning Program. The program was designed and implemented by male doctors and policy-makers from the beginning. The women’s birth control movement, which existed until the end of the 1950s, came to an end with the military coup. The military regime excluded female organizations from the program, and the international organizations represented by the International Planned Parenthood Federation focused on population control projects under the order of Cold War rather than women’s right to control childbirth according to their will. Given the change of circumstances, the initiative of the plan was transferred to a group of male doctors who had acquired knowledge of preventive medicine, population theory, and had become proficient in English by studying abroad; they emerged as a point of contact between the international order and Korea. Furthermore, they took over key posts in the public and private sectors. The introduction of laparoscopy strengthened the male dominance of the program. In the 1960s, although a group of male doctors led the plan’s design and supervision, it was the women who were tasked with its implementation in the field. Family planning agents were in charge of inserting the intrauterine devices and providing guidance on the usage of oral contraceptives as well as promoting and enlightening the program. The situation changed with the popularization of laparoscopic tubal sterilization. As the program was reorganized to focus on laparoscopic surgery, the role of female agents was reduced to promoting the new technology, while obstetricians—predominantly male—emerged as the main actors intervening in women’s bodies. Thus, laparoscopy was a technology that reproduced and reinforced gender inequality in terms of the plan’s targets and initiatives. Laparoscopy also had an impact on the Korean obstetrician community. In short, it was the basis of technological catch-up. Elite obstetricians in Korea who joined the international trends of obstetrics continued to face new technologies, such as surgical microscopes used for microsurgery (e.g., tubal reanastomosis) and in vitro fertilization (IVF). Encouraged by the introduction of laparoscopy, obstetricians in Korea once again tried to keep up with the trends in global obstetrics and attained some success. This was because laparoscopy created the necessity and the possibility of technological catch-up. The popularization of laparoscopic tubal sterilization meant an increase in the demand to restore fertility. Although the proportion of those who wanted reversal surgery was not significantly high, the absolute number was not small because sterilization was performed on hundreds of thousands of people every year. This resulted in the demand for tubal reanastomosis and IVF. Laparoscopy created the possibility of introducing new reproductive technologies also. Microscopic tubal reversal was transferred to Korea through the same network by which laparoscopic tubal sterilization had been introduced. The main agents of technical education and financial support, and the operation of the training programs, were identical. The case of IVF was slightly different. In the case of IVF, universities and laboratories were competing to achieve success first. In this competitive structure, nobody wanted to disclose their technology; therefore, it was not easy for medical professionals of developing countries to go abroad to learn new skills. However, the human network established during the introduction of laparoscopy enabled many Korean obstetricians to seek training overseas, thereby introducing IVF technology to Korea. In conclusion, laparoscopy was developed and spread through the unique social structures of the time, whilst reproducing and strengthening them at the same time. First, in the political order of the Cold War, laparoscopy was rediscovered and improved as a means of intervening in the population of developing countries and then became the basis for the continuation of population control projects. Second, in the patriarchal setup of Korea, laparoscopy was introduced through the Family Planning Program assuming women as the main target of the program; further, the spread of laparoscopic sterilization circularly strengthened this assumption and the dominance of male doctors. Finally, in the context of the aspirations to high technologies of medical professionals in Korea, laparoscopy could defeat competing technologies and spread quickly; moreover, it functioned as a basis for technological catch-up. In short, laparoscopy was a technology that mediated and reinforced the multilayered structures of the Cold War, gender politics, and technological aspirations. 이 논문은 1970년대와 1980년대 한국에서 복강경 기술이 도입되고 확산하는 과정과 그것이 한국 사회에 미친 영향을 역사적으로 분석하였다. 문제의식은 다음의 세 가지였다. 첫 번째, 이미 다른 피임 기술이 보급되어 있던 상황에서, 복강경 기술이 한국으로 도입되고 확산할 수 있었던 까닭은 무엇인가. 두 번째, 이렇게 도입되고 확산한 복강경 기술은 한국 가족계획 사업에 어떤 영향을 주었는가. 세 번째, 복강경 기술은 이후 한국의 산부인과학계에 어떠한 영향을 주었는가. 이를 밝히기 위해 1970년대와 1980년대 당시 한국과 미국에서 생산된 여러 정부 문건과 비정부기구 보고서, 의학 연구 논문 등을 살펴보았으며, 그러한 탐구의 결과 다음과 같은 결론을 내릴 수 있었다. 먼저 복강경 기술이 한국으로 도입되고 확산할 수 있었던 이유는 크게 세 가지였다. 첫 번째는 난관 불임 수술이라는 새로운 피임 기술의 필요성과 가능성이 갖추어졌기 때문이다. 1970년대에 들어서면서 기존에 사용되던 자궁내장치와 경구피임약, 정관 불임 수술 등의 방법은 기술 자체의 결함과 근거 없는 목표량 설정에 따른 잦은 부작용, 심리적 저항 등의 한계를 노출했다. 이에 따라 많은 의학자와 인구학자는 난관 불임 수술이라는 대안 기술에 주목했다. 물론 난관 불임 수술은 수술실과 입원실이라는 물적 조건을 갖춘 병원에서만 시행 가능한 까다로운 기술이었다. 하지만 한국의 경우 도시 가족계획 사업의 시행으로 병원이 사업의 새로운 중심으로 부상하고, 여기에 1970년대 중반에 도입된 복강경이 수술의 물적 조건을 완화하면서, 이러한 한계는 상당 부분 극복될 수 있었다. 두 번째는 복강경 기술이 미국과 한국 양국 정부와 의학자의 이해관계에 고루 부합하였기 때문이다. 기존의 피임 기술이 한계를 노출하는 상황 속에서, 미국 정부와 한국 정부는 복강경 난관 불임 수술을 시행함으로써 인구 조절 사업을 통한 자유 진영의 수호와 경제 개발 계획을 지속할 수 있었다. 복강경 기술은 양국 의학자의 이해에도 합치하였다. 피임 기술의 개발과 확산을 주도하던 선진국의 여러 의학자는 수술법을 표준화하여 보급하고 규격화된 양식으로 결과를 보고받는 ‘수술실의 확장’을 통해 막대한 양의 임상례를 확보할 수 있었다. 한국의 의학자 역시 복강경 수술의 표준화로 이어진 양국의 연결망을 바탕으로 선진국의 기술을 이전받는 동시에, 다량의 임상례를 생산하는 자로서의 권위를 누릴 수 있었다. 마지막은 복강경이 개발도상국의 상황에 맞게 개량되었기 때문이다. 난관 불임 수술에 사용되기 시작한 초기만 해도, 복강경은 개발도상국의 환경에 적합한 기술이 아니었다. 복강경은 기대만큼 안전하지도, 기대만큼 저렴하지도 못했다. 이를 해결하기 위하여, 국제개발처와 포드 재단 등의 관민 기관과 여러 의학자가 복강경의 개량에 뛰어들었다. 복잡한 부품은 간단한 부품으로 교체되었고, 위험한 방식은 안전한 방식으로 대체되었다. 이렇게 난관 불임 수술의 필요성과 가능성이 갖추어지고, 기술 이전을 향한 이해관계가 중첩되는 동시에, 이전 대상국의 환경에 따라 복강경이 개량됨에 따라, 복강경은 급속도로 이전되고 확산할 수 있었다. 한국에 복강경 기술이 이전된 이후 복강경을 이용한 난관 불임 수술은 다른 피임 기술을 빠르게 추격하였고, 마침내 1980년대 초반에 이르러 수위(首位)를 차지했다. 두 번째와 세 번째 문제의식은 복강경 기술이 한국 사회에 미친 영향에 해당한다. 먼저 가족계획 사업에 끼친 영향이다. 요컨대 복강경은 남성으로 치우친 사업의 젠더 질서를 고착화하고 심화하였다. 복강경은 사업의 대상을 여성으로 고정하는 결과를 가져왔다. 사업을 주도하던 양대 세력인 정부 관료와 의사 집단은 사업의 초기부터 줄곧 여성을 대상으로 삼았다. 자궁내장치와 경구피임약의 확산이 정체하면서 정관 불임 수술이 대안으로 떠올랐지만, 복강경의 도입과 함께 사업은 다시 여성으로 집중되었다. 사업의 주도권 역시 마찬가지였다. 남성 의사 집단이 사업의 설계와 감독을 주도하였지만, 복강경이 도입되기 전까지만 해도 현장에서의 실행만큼은 여성의 몫이었다. 그러나 사업이 복강경을 중심으로 재편되며 여성 요원의 역할은 새로운 기술을 홍보하고 안내하는 수준으로 축소되었고, 남성이 다수이던 산부인과 의사가 여성의 신체에 개입하는 주요 행위자가 되었다. 이렇게 복강경은 사업의 대상과 주도권의 측면에서, 젠더 불평등을 재생산하고 확대하였다. 다음은 복강경 기술이 한국 산부인과학계에 미친 영향이다. 복강경을 계기로 산부인과학의 국제적 조류에 합류한 한국의 엘리트 산부인과 의사는 계속해서 수술 현미경이나 체외수정과 같은 새로운 기술을 도입하였다. 이는 복강경이 기술 추격의 필요성과 가능성을 만들어낸 결과였다. 먼저 복강경은 신기술이 도입되어야 할 필요성을 창출했다. 복강경의 확산에 따른 난관 불임 수술의 보급은 다시 생식능력을 복원하려는 수요의 성장으로 이어졌다. 복강경은 새로운 기술이 도입되는 가능성이기도 했다. 현미경을 이용한 난관 복원 수술은 복강경 난관 불임 수술을 도입하던 연결망을 통해 한국으로 이전되었고, 체외 수정 역시 복강경 기술의 이전 과정에서 생성된 인적 연결망을 바탕으로 도입될 수 있었다. 이처럼 복강경은 당대의 고유한 사회 구조를 매개로 만들어지고 퍼져 나갔고, 동시에 이러한 구조를 재생산하고 강화하였다. 먼저 오래된 기술인 복강경은 냉전의 정치 상황 속에서 개발도상국의 인구에 개입하는 수단으로 재조명되며 비로소 개량될 수 있었고, 이렇게 개량되어 보급됨으로써 다시 인구 조절 사업을 이어나가는 바탕이 되었다. 또한 남성으로 치우친 한국의 젠더 질서 속에서 복강경은 여성을 사업의 주요 대상으로 상정하는 사업 기조를 매개로 한국에 도입되어, 다시금 여성을 사업의 대상으로 고정하는 동시에, 남성 의사의 주도권을 강화하기도 했다. 마지막으로 복강경은 선진국을 향한 여러 엘리트 의학자의 열망에 힘입어 빠르게 이전되고 확산하였으며, 이는 이후 수술 현미경과 체외수정 기술을 추격하는 기반으로 작동하였다. 요컨대 복강경은 냉전과 젠더 불평등, 그리고 선진 기술을 향한 선망이라는 당대의 구조를 매개하고 강화하는 기술이었다.open박

HgCdTe 내부로의 인듐 고속열확산과 적외선 감지 소자 제작

학위논문(박사) - 한국과학기술원 : 전기및전자공학과, 1997.2, [ iv, 129 p. ]A new p-n junction formation method on p-HgCdTe by indium rapid thermal diffusion and a new plausible structure of two color IR detector are proposed. Rapid thermal diffusion of indium into HgCdTe (x=0.30) is studied over the temperature range of 100 - 200 ℃, for 5 - 600 seconds. It is observed that there are two diffusion components, the first one being an erfc function fitted atomic component and the other being an exponentially fitted fast component. From the Arrhenius plot, the diffusion coefficients of indium by RTD in HgCdTe (x=0.30) were fitted by $D(T) = 1.45 × 10^{-2} \exp(-0.772(eV)/kT) ㎠/s$. The activation energy is 0.772 eV. From the differential Hall and conductivity measurements at 77K, it is observed that not all of the diffused indium is activated as donors and that the portion of activated indium depends heavily on the indium concentration. Large suppression of reverse bias leakage current is archived in the RTD photodiodes in comparison with ion implanted HgCdTe photodiode. The suppression of defects generation in junction formation by RTD might give the p-n junctions with reduced traps, resulting the suppression of reverse bias leakage current. The extracted minority carrier lifetime from plot of R0A versus 1000/T obtained from RTD diode is 6 times larger than that from ion implanted diodes. This means that the trap density in the RTD diodes is reduced by 6 times. This result suggest that junction formation by RTD is more advantageous than junction formation by ion implantation for the future high density IRFPA. We propose a new n-p-N structure simultaneously and independently operable two color (MW/LWIR and SW/MWIR combination) detector. The proposed two color detector has the back-to-back diode structure of the n-p-N-HgCdTe on CdZnTe substrate. The potential barrier in p-N heterojunction plays critical role in that it prevents photogenerated minority carriers in p-HgCdTe from diffusing to N-HgCdTe. The heterojunction analysis with ...한국과학기술원 : 전기및전자공학과

Development of a Method for Manufacturing External Quality Assessment Material for Genetic Testing of Solid Tumors Using Mutant and Wild-Type Cell Lines

Background: DNA extracted from mutant cell lines is frequently used as an external quality assessment (EQA) material for genetic testing of solid tumors because it is easy to obtain. However, the proportion of mutations in cell lines is different from that in actual tumor samples. In this study, mixtures of mutant DNA and wild-type DNA mimicking patient samples were analyzed to optimize the amount of mutant DNA in EQA specimens. Methods: Four cell lines harboring the selected mutation were cultured, and genomic DNA was extracted from cultured cells. Wild-type cell line DNA was prepared in the same manner. Diluted samples were prepared by mixing each mutant cell line DNA and wild-type cell line DNA at different ratios. Sanger sequencing of target variants was performed. For reliability, sequencing was repeated three times and read by two readers. The cutoff was based on the lowest proportion of mutant DNA that was determined to be positive in all three experiments. Results: The cutoffs of mutant cell line DNA ratios were 10%, 5%, 25%, and 25% for KRAS G12C, EGFR exon 19 deletion, EGFR T790M, and BRAF V600E, respectively. For the cell lines harboring EGFR T790M and BRAF V600E, the mutant fraction was not 100%. Conclusions: When manufacturing EQA material for solid tumor genetic testing, consistent results can be obtained if the mutant proportion is 10% or more. In addition, the mutant allele frequency of the cell line should be checked in advance to guarantee that EQA materials contain enough mutant DNA