Design and microfabrication of a miniature fiber optic probe with integrated lenses and mirrors for Raman and fluorescence measurements
Fiber optics coupled to components such as lenses and mirrors have seen extensive use as probes for Raman and fluorescence measurements. Probes can be placed directly on or into a sample to allow for simplified and remote application of these optical techniques. The size and complexity of such probes however limits their application. We have used microfabrication in polydimethylsiloxane (PDMS) to create compact probes that are 0.5 mm thick by 1 mm wide. The miniature probes incorporate pre-aligned mirrors, lenses, and two fiber optic guides to allow separate input and output optical paths suitable for Raman and fluorescence spectroscopy measurements. The fabricated probe has 70 % unidirectional optical throughput and generates no spectral artifacts in the wavelength range of 200 to 800 nm. The probe is demonstrated for measurement of fluorescence within microfluidic devices and collection of Raman spectra from a pharmaceutical tablet. The fluorescence limit of detection was 6 nM when using the probe to measure resorufin inside a 150-μm inner diameter glass capillary, 100 nM for resorufin in a 60-μm-deep × 100-μm-wide PDMS channel, and 11 nM for fluorescein in a 25-μm-deep × 80-μm-wide glass channel. It is demonstrated that the same probe can be used on different sample types, e.g., microfluidic chips and tablets. Compared to existing Raman and fluorescence probes, the microfabricated probes enable measurement in smaller spaces and have lower fabrication cost.
KeywordsMicrofabrication/microfluidics Miniaturized optical probe Spectroscopy Remote application Diagnostics
We acknowledge Professor Fred Terry (EECS, UMich) for measuring the refractive index of PDMS, Brian Johnson (CHE, UMich) for the assistance with multilayer mask alignment, Jim Tedesco (Kaiser Optical Systems) for the help with Zemax modelling, and Rafal Pawluczyk (Fiber Tech Optical) for the advice and donation of various supplies in support of this project. This work was supported by NIH R37DK46960 & R37EB003320 (R.T.K.) and R01AR056646 (M.D.M.).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 6.Shim MG, Song L-MWK, Marcon NE, Wilson BC. In vivo near-infrared Raman spectroscopy: demonstration of feasibility during clinical gastrointestinal endoscopy. Photochem Photobiol. 2000;72(1):146–50.Google Scholar
- 11.Grimbergen MCM, van Swol CFP, Draga ROP, van Diest P, Verdaasdonk RM, Stone N, Bosch JHLR. Bladder cancer diagnosis during cystoscopy using Raman spectroscopy. In SPIE; 2009;716114 – 6.Google Scholar
- 12.Latka I, Dochow S, Krafft C, Dietzek B, Bartelt H, Popp J. Development of a fiber-based Raman probe for clinical diagnostics. In: Ramanujam N, Jürgen P, editors. Clinical and biomedical spectroscopy and imaging II. Munich: SPIE and Optical Society of America; 2011. 80872D-1-8.Google Scholar
- 34.Rosenauer M, Vellekoop MJ. An adjustable optofluidic micro lens enhancing single cell analysis systems. In: Dössel O, Schlegel WC, editors. World congress on medical physics and biomedical engineering, September 7–12, 2009. Munich: Springer; 2010. p. 185–8. IFMBE Proceedings.Google Scholar
- 44.Sapuppo F, Schembri F, Fortuna L, Llobera A, Bucolo M. A polymeric micro-optical system for the spatial monitoring in two-phase microfluidics. Microfluid Nanofluid. 2011;12(1–4):165–74.Google Scholar
- 50.Free glycerol colorimetric/fluorometric assay kit. In: The BioVision index of manuals online. BioVision Incorporated. 2014. http://www.biovision.com/manuals/K630.pdf. Accessed 24 Jan 2015.