Microchip for HBV testing using HIV-infected blood samples

使用感染艾滋病毒的血液样本进行乙型肝炎病毒检测的微芯片

• 批准号: 10767533
• 负责人: Hadi Shafiee
• 金额: $ 50万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-06 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10767533
• 关键词: Antibodies; Antigens; Biological Assay; Blood Volume; Blood specimen; Caring; Cellular Phone; Chronic; Cirrhosis; Complex; Cytomegalovirus; DNA; Detection; Development; Devices; Disease Management; Fingers; Fumarates; Gases; Goals; HIV; HIV Infections; Hepatitis; Hepatitis B Infection; Hepatitis B Virus; Hepatitis C; Herpesviridae; Human Herpesvirus 4; Human Herpesvirus 8; Hydrogen Peroxide; Individual; Infection; Influenza; Knowledge; Label; Laboratories; Link; Liver; Malaria; Methods; Microfluidic Microchips; Monitor; Morbidity - disease rate; Nanotechnology; Nucleic Acids; Optics; Patients; Performance; Persons; Platinum; Play; Point of Care Technology; Polymerase Chain Reaction; Primary carcinoma of the liver cells; Process; RNA; Regimen; Reverse Transcription; Risk; Role; Saliva; Sampling; Seminal fluid; Sensitivity and Specificity; Serology test; Services; Signal Transduction; Simplexvirus; Site; Specificity; System; Technology; Tenofovir; Testing; Treatment Efficacy; Treatment Failure; Treatment outcome; Urine; Venipunctures; Viral Load result; Virus; Virus Diseases; Whole Blood; Work; acute infection; clinically relevant; co-infection; cost; detection platform; diagnostic tool; disease diagnosis; empowerment; high risk; improved; infection risk; microchip; mortality risk; multiplex diagnostics; nanoparticle; nanoprobe; point of care; point of care testing; portability; rapid test; screening; technology platform; tool; transmission process

PROJECT SUMMARY It is estimated that more than 240 million people are living with HBV infection and more than 36 million people with HIV infection worldwide, of which up to 60% of HBV-infected and 30% of HIV-infected individuals are unaware of their infection status. HBV coinfcetion in HIV-infected patients is linked to increased risk of cirrhosis and Hepatocellular carcinoma (HCC), higher rate of chronicity and occult HBV, and higher rate of liver-related morbidity. Accurate and timely knowledge of HBV/HIV coinfection status is essential to select the optimal ART regimen and tenofovir disoproxil fumarate (TDF) as well as treatment monitoring to identify if treatment switch is required. Previous studies showed that simultaneous detection of HIV and HBV using on-site POC tests can significantly improve the screening process and linkage to care for individuals at high risk for chronic viral infections. In addition, the undiagnosed, untreated, infected individuals can play a significant role in infection transmission to others. If untreated, the infection can lead to advanced stages, which increases the risk of mortality. The lack of appropriate diagnostic tools especially for people at high risk of infection is one of the reasons for the infection unawareness. The development of point-of-care (POC) multiplexed diagnostics is crucial in expanding hepatitis testing and disease management services for individuals with HIV/HBV co- infection in a timely manner. Viral load testing is the most accurate and preferred approach for HIV and HBV detection and treatment monitoring. Nucleic acid-based assays are currently used for viral load testing for disease diagnosis and treatment efficacy monitoring, however, these assays are still relatively expensive, laboratory-based, and technically complex. Multiplexing HIV/HBV using nucleic acid-based methods is also challenging due to simultaneous detection of RNA (HIV) and DNA (HBV) target molecules. Furthermore, current POC rapid tests (dipsticks) target antibodies/antigens against HIV/HBV generated after infection, cannot detect treatment failure and acute infection, and have low sensitivity/specificity. Thus, to increase access to HIV/HBV care with regular treatment monitoring and to improve treatment outcomes, there is an urgent need for inexpensive, rapid, sensitive, and specific HIV/HBV viral load testing tools at the POC. The main goal of this highly interdisciplinary project is developing a portable nanotechnology-empowered cellphone-based system for rapid (<30 minutes) multiplexing HIV/HBV in fingerprick volume (<100 µL) of whole blood placed on an inexpensive (<$2), disposable, and mass-producible microfluidic device. In our proposed method, (i) target viruses are captured on-chip using highly specific envelope antibodies, (ii) captured viruses are labeled with Pt nanoparticles conjugated with respective antibodies, (iii) Pt-labeled captured viruses generate bubbles through gas formation of Pt nanoparticles in the presence of hydrogen peroxide on-chip, (iv) the bubbles can be quantified using a low-cost (<$4) cellphone optical attachment for quantitative/qualitative viral load testing.

项目总结 据估计，超过2.4亿人感染了乙肝病毒，超过3600万人感染了 全世界感染艾滋病毒的人，其中高达60%的乙肝病毒感染者和30%的艾滋病毒感染者是 不知道自己的感染状况。HIV感染患者中的乙肝病毒感染与肝硬变风险增加有关 和肝细胞癌，慢性和隐匿性乙肝的比率较高，与肝脏相关的比率较高 发病率。准确和及时地了解乙肝病毒/艾滋病病毒的感染状况对于选择最佳的抗逆转录病毒治疗至关重要。 方案和富马酸替诺福韦(TDF)以及治疗监测，以确定治疗是否切换 是必需的。以前的研究表明，使用现场POC测试同时检测艾滋病毒和乙肝病毒可以 显著改善筛查程序和联系，以照顾慢性病毒高危人群 感染。此外，未确诊、未治疗的感染者可能在感染中发挥重要作用。 传播给其他人。如果不治疗，感染可能会导致晚期，这增加了患上 死亡率。缺乏适当的诊断工具，特别是对感染高危人群而言，是 感染原因不明。医疗点(POC)多路传输诊断的发展是 为艾滋病毒/乙肝病毒携带者扩展肝炎检测和疾病管理服务至关重要 及时感染。病毒载量检测是检测艾滋病毒和乙肝病毒最准确和最受欢迎的方法 检测和治疗监测。目前，基于核酸的检测方法用于病毒载量检测 疾病诊断和治疗效果监测，然而，这些检测仍然相对昂贵， 以实验室为基础，技术复杂。使用基于核酸的方法来多路传输艾滋病毒/乙肝病毒也是 由于同时检测到RNA(艾滋病毒)和DNA(乙肝病毒)靶分子，因此具有挑战性。此外， 目前的POC快速检测(试纸)以感染后产生的针对HIV/HBV病毒的抗体/抗原为目标， 无法检测到治疗失败和急性感染，敏感性/特异性较低。因此，要增加 通过定期治疗监测获得艾滋病毒/乙肝病毒护理，并改善治疗结果，有 POC迫切需要廉价、快速、敏感和特定的艾滋病毒/乙肝病毒载量检测工具。这个 这个高度跨学科的项目的主要目标是开发一种便携式纳米技术-赋能 基于手机的快速(&lt；30分钟)指针量(&lt；100微米L)艾滋病毒/乙肝病毒复合系统 血液放置在一种廉价(2英镑)、一次性、可批量生产的微流控设备上。在我们提议的 方法，(I)使用高度特异的包膜抗体在芯片上捕获目标病毒，(Ii)捕获的病毒 用与相应抗体结合的铂纳米颗粒标记，(Iii)铂标记捕获的病毒 在片上过氧化氢存在下，通过铂纳米颗粒的气体形成产生气泡，(Iv) 可以使用低成本(4美元)的手机光学附件对气泡进行量化/定性 病毒载量测试。

项目成果

Advancements in the future of automating micromanipulation techniques in the IVF laboratory using deep convolutional neural networks.

使用深度卷积神经网络在 IVF 实验室中实现自动化显微操作技术的未来进展。

• DOI: 10.1007/s10815-022-02685-9
• 发表时间: 2023
• 期刊: Journal of assisted reproduction and genetics
• 影响因子: 3.1
• 作者: Jiang,VictoriaS;Kartik,Deeksha;Thirumalaraju,Prudhvi;Kandula,Hemanth;Kanakasabapathy,ManojKumar;Souter,Irene;Dimitriadis,Irene;Bormann,CharlesL;Shafiee,Hadi
• 通讯作者: Shafiee,Hadi

Consistency and objectivity of automated embryo assessments using deep neural networks.

• DOI: 10.1016/j.fertnstert.2019.12.004
• 发表时间: 2020-04
• 期刊: Fertility and sterility
• 影响因子: 6.7
• 作者: Bormann CL;Thirumalaraju P;Kanakasabapathy MK;Kandula H;Souter I;Dimitriadis I;Gupta R;Pooniwala R;Shafiee H
• 通讯作者: Shafiee H

Performance of a deep learning based neural network in the selection of human blastocysts for implantation.

• DOI: 10.7554/elife.55301
• 发表时间: 2020-09-15
• 期刊: eLife
• 影响因子: 7.7
• 作者: Bormann CL;Kanakasabapathy MK;Thirumalaraju P;Gupta R;Pooniwala R;Kandula H;Hariton E;Souter I;Dimitriadis I;Ramirez LB;Curchoe CL;Swain J;Boehnlein LM;Shafiee H
• 通讯作者: Shafiee H

Virus detection using nanoparticles and deep neural network-enabled smartphone system.

使用纳米颗粒和支持神经网络的智能手机系统的病毒检测。

• DOI: 10.1126/sciadv.abd5354
• 发表时间: 2020-12
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Draz MS;Vasan A;Muthupandian A;Kanakasabapathy MK;Thirumalaraju P;Sreeram A;Krishnakumar S;Yogesh V;Lin W;Yu XG;Chung RT;Shafiee H
• 通讯作者: Shafiee H

Adaptive adversarial neural networks for the analysis of lossy and domain-shifted datasets of medical images.

• DOI: 10.1038/s41551-021-00733-w
• 发表时间: 2021-06
• 期刊: Nature biomedical engineering
• 影响因子: 28.1
• 作者: Kanakasabapathy MK;Thirumalaraju P;Kandula H;Doshi F;Sivakumar AD;Kartik D;Gupta R;Pooniwala R;Branda JA;Tsibris AM;Kuritzkes DR;Petrozza JC;Bormann CL;Shafiee H
• 通讯作者: Shafiee H