Lab on a Chip : advances in packaging for MEMS and Lab on a Chip

Multi-Material Micro Manufacture W. Menz, S. Dimov and B. Fillon (Eds.) © 2006 Elsevier Ltd. All rights reserved

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Lab on a Chip : advances in packaging for MEMS and Lab on a Chip Dr. Fabien Sauter-Staracea, C. Puddaa, C. Delattrea, H. Jeansona, C. Gillotb, N. Sarruta, O. Constantina, R. Blanca a

: CEA, LETI, Department Microtechnology for Biology and Health-care, France b : CEA-LETI, Department Heterogeneous Silicon Integration, France

Abstract In the field of bioMems or Lab on a Chip, one may have to handle fluid exchanges even at high pressure, moving parts, temperature sensitive probes. This specificity triggers huge packaging issues because most of the packaging techniques inherited from the microelectronic require thermal cycles at temperature above 350°C. In this paper, we first present the requirement of representative lab on chip projects carried out at the LETI in order to introduce two specific solutions of this field. Afterwards we present a brief review of the packaging processes used in the MEMS facilities eventually and introduce low temperature packaging processes developed at the CEA Leti to process lab on chip with MEMS and BioMEMS. We intend to develop robust and collective solutions (wafer level packaging). The first solution relies on a thin film approach develop for MEMS using silicon nitride cap on a sacrificial layer. The second one was especially designed for temperature sensitive lab on chips hence can be carried out at room temperature. Keywords: packaging, lab on chip, thin film, in line screen-printing

Introduction The fabrication processes of MEMS (micro electro mechanical system) are largely based on silicon technology derived from the microelectronic industry. However several parameters remains quite different from the processes of microelectronics. First as they are structural elements made or derived of semi conductor materials, the thickness of theses layers whether they are dielectric or conductive can be in the range of tens of microns or hundreds of microns, whence specific etching procedures and longer runs. Second interactions between the macro world and these devices are not restricted to electrons or photons exchanges. In our department we may have to handle fluid exchanges even high pressure fluids, moving parts. This specificity triggers huge packaging issues. In this paper, we first present the requirement of representative biochip projects carried out at the LETI in order to introduce two specific solutions of this field afterwards we present a brief review of the packaging processes used in the MEMS facilities eventually we discuss low temperature packaging processes developed at the CEA Leti to process lab on chip for MEMS and BioMEMS. We intend to develop robust and collective solutions such as wafer level packaging. The first solution is based on an innovative in line glue process to package temperature sensitive biochips. A semi-automatic equipment is used to deposit through a mesh an accurate volume of UV curable glue of the top of a wafer with deep etched structures. Then the wafer is aligned with the top wafer (polycarbonate, SiO2 glass or Pyrex) using dedicated alignment features and then bonded and cured using insulation in vacuum contact. The second solution is an above IC process, this solution is a thin film packaging process and is well suited for ASIC or MEMS that can bare a 300°C process.

1. Several representative Constraints in projects using microfluidic 1.1

Biocompatibility Since our applications deals with lipid bilayer, DNA strands and even living cells we have to restrict ourselves to biocompatible materials. Hopefully silicon technologies are well-suited for these fields since silicon is naturally oxidized in air or in water to silicon dioxide which is the major

Fig. 1: Enzymatic protein digestion microreactor. component of glass. Based on a huge amount of data, we can use silicon for in-vitro and even in-vivo devices. Obviously glass substrate, synthetic silica or borosilicate such as Pyrex can also be used. Consequently the strait forward materials of microelectronic that are silicon, silicon dioxide and silicon nitride fit perfectly with the biocompatibility constraints with a small limitation for long term stability of silicon in saline solution. This problem is said 1 to be reduced by diffusing a boron etch stop[ ].

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Biochiplab- (high pressure)

This project is based on a liquid chromatography reactor. This biological sample is introduced in the reactor at high pressure commonly 20 bar and is forced to flow through a forest of pillars made by silicon deep etching. In order to obtain a high density reactor, micropillars of 10 µm diagonal, 15µm pitch and 50µm or 27µm height were etched in silicon[2]. Controlled thermal oxidation decreases the space between micropillars and allows electrical isolation of the channel essential for electroosmotic pumping. For digestion reactors, the micro-pillars have a hexagonal section (see in Fig. 1). For LC micro-columns, the micro-pillars have a square section and the pillar to pillar space is 1,5 µm (see in Fig. 2).

- To the Agro-food Community: To demonstrate advantages of the MST, AmI and wireless solutions for new and/or current analytical tools and test methodologies, as well as their impact on improved farming. - To the Microsystems industrial community: To show that Agrofood is a good niche market for MST solutions. - To the SME and foundries: To develop demonstrators and market plans that show viability and lower the risks of future market access- To the MST scientific community: To give a path for take-ups, start-ups. A set of detection targets of vital importance has been also identified by the same relevant food industry representatives. In this direction, the presence of chemical substances (antibiotics, pesticides and mycotoxins) and of life organisms (pathogens ) has been considered the most relevant issues to be addressed from the safety point of view. The project restricts itself to a realistic limited number of applications that are nevertheless representative of a broad range of problematic involving solid and liquid products: milk, dairy products, fruits and fruit juices, wine, and fish[3]. Our lab is involved in the detection of antibiotics in milk which can trigger allergies or reduce the efficiency of human treatments based on antibiotics. Note the farmers are allowed to use antibiotics but the milk of these cows must be discarded for a strict period. A monitoring of the collected milk enable the control of this period of time. The analytical concept is based on heterogeneous sandwich immunoassay and planar optical Wave guides (see in Fig. 3): Label

Laser

Antibody Photoreceiver Magnetic bead Planar Wave guides Target antigen

Fig. 2: LC micro-columns A transparent Pyrex cap (CORNING 7740) containing inlet and outlet holes was then sealed on the microreactor by molecular bonding. Standard microfluidic connectors (NanoportTM assemblies) were glued on the top of the cap opposite to the etched holes; they can be used either for electroosmotic or hydrodynamic flows. For electroosmosis, platinum electrodes were introduced directly into the connectors while for hydrodynamic pumping, another connecting part allows the fixation of a silica capillary of 360µm external diameter. 1.3

GoodFood

The GoodFood project is an integrated project of the sixth framework program (information society technologies). This project deals with the security and the tracking for quality assurance for the agrofood industry. GoodFood aims at increasing awareness at different levels: - To the citizens: To show that Ambient Intelligence (AmI) and ubiquitous sensing can help on increasing food safety and quality.

Fig. 3: Micro- Analytical concept of sandwich immunoassay and planar optical Wave guides. An example of magnetic bead based immunoassay concept is shown in Fig. 4. Antibody coated beads are introduced to the micro component (1) and separated by applying a magnetic field (2). While holding the antibody coated beads, antibiotics are injected into the microchannel (3). Only target antibiotics are immobilized due to antibody/antibiotic reaction. Other antibiotic get washed out with the flow (4). Next, the antibody coated beads with the antibiotics are transported to the detection chamber (5). The antibody coated beads with the antibiotics bound at the secondary antibodies fix on planar optical Wave guides. (6) The evanescent field-based fluorescence detection is performed.

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(1)

(3)

(2)

(4)

(5)

(6)

Fig. 4: Conceptual illustration of magnetic bead based immunoassay procedure using magnetic bead approach The paradigm of the detection of the following: the milk sample is introduced in the microsystem, agitation or simple diffusion (depending on the authorized time) occurs so that the complementary antibody capture the antibiotics. The complementary antibody is a sandwich made of the complementary antigen with a fluorescent label and eventually the sandwich is grafted on a magnetic beads using an interaction such as biotin / streptavidine. Using a focused magnet the beads are gathered and driven to a smaller chamber which amounts to a 100 concentration factor. Then an elution based on thermal actuation or a change of the ionic force in the chamber break the link between the beads and the target labeled. Eventually the targets react with their complementary grafted on a wave guide. The evanescent wave excite the fluorophore and enable the detection of the antibiotics. The last sequence of capture is based on antigen grafted on the wave guides, which triggers a major constraint: the sealing of the silicon wafer and the glass substrate including the wave guide must be very friendly to the antigen, i.e. the sealing temperature remain as low as possible. 2

Standards wafer level Solutions

Hereafter we describe very briefly three wellknown bonding principles by decreasing temperature. Pros and cons of these techniques are highlighted and account for the development of new low temperature bonding process. 2.1

Silicon Direct Bonding, Pros and cons

Silicon direct bonding is by far the more strait forward way to obtain a bond between two silicon wafers. This process is well know and is described in Microfabrication handbook such as Microfabrication fundamentals of Dr. Marc Madou[4]. The principle is to create a hydrogen bond between two SiO2 surfaces treated with a Brown solution or an oxygen Plasma (silanol Si-OH), which after a high temperature stage (1000 °C) under secondary vacuum (10-6 Pa) turns to a Si-O-Si bond. The fracture strength of the obtained stack is in the range of 20 MPa. This process is front end compatible but very demanding on the cleaning processes to obtain a good bonding and there are obvious limits due to the bonding temperature. 2.2

Eutectic, Pros and cons

Eutectic bonding is based on the creation of a SiAu layer to bond two silicon wafers (with a gold interface) or silica with a gold deposit. The mean fracture is as high as 150 MPa according to Tiensuu5 which is much higher than the silicon direct bonding.

There are important drawbacks with this technique. First the process is not compatible with most of the microelectronic fab since gold contamination is a major issue in Front-end clean rooms. Second there are large thermal stress associated to the thermal cycle whence failure and reliability issues. 2.3

Anodic, Pros and cons

Anodic bonding requires the contact of the silicon and a borosilicate glass substrate. Under 350 °C degree, and a voltage between 300 and 500V (at the Léti), one create a very robust bond. Glass such as Pyrex Corning 7740 are perfect for this technique since they are borosilicate glass and their coefficient of thermal expansion match the one of silicon (round 3.4E-6 °K-1). Consequently there are no thermal stress in the wafers. Note that the electrochemical, electrostatic and thermal mechanism could be combined to explain the anodic bonding. The exact phenomena is not perfectly understood, but migration of the sodium ions of the borosilicate glass in the silicon creates depletion which results in a high electrostatic force. These three techniques require a wafer level packaging for sake of uniformity of the load, or the electrical field. This can be a drawback if to reduce costs a strategy of Multi Project Wafers (MPW) is chosen. 2.4

Polymer bonding using a laminated photoresist (Ordyl)

Laminated UV curable polymer such as Ordyl (SY 330 supplied by Elga Europe) gave good results when used to thermally bond above the glass transition a layer of Ordyl and to Indium Tin Oxide. It is also possible to bond two layers of Ordyl layers using thermo compression (load 6 kg.cm-2 at 70°C during half an hour and afterwards without load at 150 °C during two hours (see in Fig. 5[6]). This technique allows watertight packaging and relatively low bonding temperature and gives excellent results compared to a SU8 photo-resist in terms of flatness a control on the whole wafer with an Altisurf 500 (supplied by Cotec) give 0.7 µm for the Ordyl vs. 5 µm for the SU8[7]. However this requires a photography, i.e. the use of a photomask and possible misalignment and the post bake is still too high for some our bio-labels.

Fig. 5: a) Double bonded wafer and double bonded microscope glass. The wafer consists of a silicon substrate, two layers of SY550 dry resist in between and a glass wafer on top. The microscope slide had one layer of SY550 resist on top and was covered by a second microscope slide. The white arrow points to an ‘unbonded’ site, which can be recognized by a change in refractive index. b). Three-lane flow profile in a fluidic network (three layers of SY330)

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3.1

Specific solutions for low temperature sealing at the CEA Leti Thin film packaging

Silicon nitride has long been used for protection of ICs against moisture. All tests to date indicate that silicon nitride is an excellent thin-film material for hermetic encapsulation even in very thin layers so long as the films are pinhole free[8]. Another way to encapsulate MEMS at wafer level have been developed by MEMS engineers, called thin film packaging[9] see in Fig. 6.. Closed cavities are formed above the devices with surface-micromachining techniques. As thin film packaging uses standard IC technologies and consumes less die area, it should offer a lower system cost than wafer bonding packaging. Moreover, it does not require wafer to wafer alignment and backside process technologies, which are not common in IC fabs. The cavity above to device is formed with a sacrificial layer recovered by a cap. Holes are opened in the cap by a standard photolithography / dry etching process. Then, the sacrificial layer is removed through the holes. Finally, a film is deposited on the cap to seal the cap holes. Sealing can be performed by solder bumping, metal evaporation or dielectric deposit. In the technology developed at Leti, we use a polymer as the sacrificial layer. It is removed by dry etching (oxygen plasma) to avoid problems induced by wet etching such as sticking or pollution. The cap is formed by a silicon oxide deposition. Hermetic sealing under vacuum is obtained by a silicon nitride deposition. The main interest of our technology is the compatibility with IC and MEMS as it is a low temperature process (<350°C).

Wafer bonding package

Thin film package Top view of an oxide cap sealed by a nitride deposition Fig. 6: silicon nitride deposition 3.2

In-line screen-printing solution The in line glue process was especially developed to package chips including bio-label (antigen, antibodies or DNA strand). These species are dramatically sensitive to temperature. Packaging temperature must remain below 80°C unfortunately none of the classical packaging technique meets this requirement. The in-line screen-printing process is based on the transfer of an amount of glue through a stencil. This process is based on an in-line screen printer supplied by Ekra¤ (model E5 STS High-Precision semiautomatic screen printer). The stencil is a mesh of Polyester as shown on the sketch in Fig. 7. Where the mesh is blank the glue is transferred through the stencil on the upper part of the substrate (hereafter so-called bottom substrate). Note that feature can be drawn on the mesh to avoid glue punctually on the wafer or to

locate alignment marks. The volume transferred on the substrate depends on the parameter of the mesh and the characteristic of the squeegee such as angle, pressure, speed. The amount of glue is of secondary importance. A common formula (Eq. 1) is given to assess the amount of transferred glue:

( )

2

vth = W ⋅D W +d

(1)

, where d is the diameter of the fiber of the mesh, W the aperture between the fibers and D the thickness of the tissue.

Sketch of mesh 1

Sketch of mesh 2

Photograph of mesh 1 Photograph of mesh 2

Fig. 7: mesh designs In our group, a design of experiment (DOE) was carried out to minimize and control the thickness of the glue. The DOE was split in two studies for a 36 experiments trials. The study highlights the effect of the distance between the squeegee and the mesh. An optimized set of parameters allowed us to obtain a thickness in the range of 2.5 µm on 100 mm wafers with a standard deviation close to 0.5 µm. This value can be compared to the 8 µm obtained with a stamping process on 8’’ wafers. Note that the glue is an UV curable epoxy supplied by Delo and chosen to be biocompatible (with respect to USP class VI standard). After the deposit of the glue on the top of the bottom wafer, a mask aligner is used to align the top wafer with the bottom one using spacer similarly to a bond alignment process like Silicon Direct Bonding. Once the wafers are aligned, a pressure is homogeneously applied to the wafers by putting the whole wafers assembly under vacuum using either a flexible membrane or a blank mask. This amounts to a 80 daN force on the Z-axis for a 4’’ wafers set. Moreover the vacuum procedure prevents the trapping of air bubble during the stacking. Once the wafers are held in contact the UV curing begins. Afterwards, the polymerization is completed in a oven under vacuum, i.e. a soft bake of several hours at 50°C. 3.2.1

Application to the GoodFood project

The GoodFood project requires a very low temperature sealing procedure, consequently it is perfectly well suited for the in-line glue process described above. In Fig. 8, we present two results of a deposition of the glue. The feature of the mesh is still

7 very clear on the left picture and one can guess that there are unglued spots. Fortunately when the substrates are in contact and put under vacuum contact the glue spots merge and tend to create a continuous layer as shown on the right. Note that the width of the channel in the thinnest zone is 100 µm.

View of the glue on a regular surface

Microfluidic channels packaged using the inline glue process. Fig. 8: Results of glue deposit on structured and bulk silicon.

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Conclusions

In this paper after an brief presentation of the usual bonding process we focused on low temperature and above IC packaging techniques. The first solution is based on an innovative in line glue process to package temperature sensitive biochips. The second solution is an above IC process, this solution is a thin film packaging process and is well suited for ASIC or MEMS that can bare a 300°C process. These techniques may become standards in the field of BioMEMS and MEMS respectively since they address a recurrent need low temperature and versatile packaging. Acknowledgements These works are developed with the help of the Nanobio program. Reference: [1] K.D. Wise, D.J. Anderson, J.F. Hetke, D.R. Kipke and K. Najafi, “Wireless implantable Microsystems, high density electronic interfaces to the nervous system”, PROCEEDINGS OF THE IEEE, VOL. 92, NO. 1, JANUARY 2004 [2] Bing He, Niall Tait and Fred Regnier, Fabrication of nanocolumns for liquid chromatography, Anal. Chem. 70, 1998, 3790-3797. [3] GoodFood: Food Safety and Quality Monitoring with Microsystems IST2002-508774 [4] M. J. Madou, Fundamentals of Microfabrication, CRC Press, Boca Raton, 2000. [5] A.L. Tiensuu et al, “in situ investigation of precise high strength micro assembliy using Au-Si eutectic bonding”, in 8th international conference on solid-state sensors and actuators (Transducers 95). pp 236-39. [6] P.Vulto, N. Glade, L. Altomare, J. Bablet, L. Del Tin, G. Medoro, I. Chartier, N. Manaresi, M. Tartagni, R.Guerrieri, Microfluidic channel fabrication in dry film resist for production and prototyping of hybrid chips, www.rsc.org/loc | Lab on a Chip. [7] I. Chartier, C. Bory, A. Fuchs, D. Freida, N. Manaresi, M. Ruty, J. Bablet, K. Gilbert, N. Sarrut, F. Baleras, C. L. Villiers and L. Fulbert, Fabrication of hybrid plastic-silicon micro-fluidic

devices for individual cell manipulation by dielectrophoresis, Proc. SPIE-Int. Soc. Opt. Eng., 2003, 5345, 7–16. [8] K. Najafi, “Micropackaging technologies for integrated microsystems: Applications to MEMS and MOEMS,” presented at the SPIE. Micromachining and Microfabrication Symp., San Jose, CA, 2003. [9] B.H. Starck, K. Najafi, "A Low-Temperature ThinFilm Electroplated Metal Vacuum Package", Journal of Microelectromechanical Systems, Vol. 13, No. 2, pp. 147-157, April, 2004.