Low-noise current readout for in vivo fluorescence detection
Abstract/Contents
- Abstract
- Post-treatment follow-up protocols for cancer patients often call for periodic hospital visits for magnetic resonance (MR), positron electron tomography (PET) or computer tomography (CT) scanning. Continuous monitoring through an implantable device would provide doctors and patients with important information between visits. With continuous monitoring, disease progression can be tracked in real-time, therapeutic regimens can be evaluated and adjusted as needed, and abnormal activity can be detected and acted on in a timely fashion. Optical molecular imaging based on fluorescence detection can provide a quantitative measure of many cellular and molecular processes of interest. Fluorescence detection is emerging as a powerful preclinical research tool, and is an attractive candidate for continuous in vivo cancer monitoring. However, in vivo fluorescence imaging is presently possible only with bulky instrumentation that does not permit monitoring of freely-moving subjects. In order to make a fluorescence detection system implantable, and thus portable, a vertical-cavity surface-emitting laser (VCSEL), a detector and a readout circuit for measuring photocurrents need to be integrated in one package. In this work, the design, implementation and testing of a current measuring circuit for fluorescence imaging is presented. The readout architecture is based on current integration using a capacitive transimpedance amplifier (CTIA), followed by analog-to-digital (A/D) conversion based on sigma-delta modulation. Unlike conventional approaches of measuring the voltage signal at the end of the current integration period, the [Sigma][Delta] modulator oversamples the output of the CTIA directly while current integration takes place. Thus, the input to the [Sigma][Delta] modulator is a voltage ramp, and the digital filter at the output of the [Sigma][Delta] modulator implements a line-fitting operation. This technique offers an improvement in the estimation of the CTIA output slope, and removes the limitation introduced in existing architectures by the sample-and-hold (S/H) stage preceding the A/D converter. The tradeoffs among noise power, integration time and oversampling ratio are examined in detail, and a method for extending the dynamic range (DR) of the system by a factor of five, even when voltage saturation occurs, is described. As an experimental demonstration, a prototype readout circuit was integrated in a 0.18-[Mu]m CMOS technology and then interfaced to a fluorescence detector. In vitro fluorescence measurements were performed, and an implantable solution made possible with miniaturized packaging of the two chips was demonstrated. This miniature package was implanted in live animals, which enabled in vivo fluorescence detection in freely-moving mice.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Heitz, Roxana Trofin |
|---|---|
| Associated with | Stanford University, Department of Electrical Engineering |
| Primary advisor | Wooley, Bruce A, 1943- |
| Thesis advisor | Wooley, Bruce A, 1943- |
| Thesis advisor | Barkin, David |
| Thesis advisor | Shenoy, Krishna V. (Krishna Vaughn) |
| Advisor | Barkin, David |
| Advisor | Shenoy, Krishna V. (Krishna Vaughn) |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Roxana Trofin Heitz. |
|---|---|
| Note | Submitted to the Department of Electrical Engineering. |
| Thesis | Ph.D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Roxana Trofin Heitz
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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