STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

Not Applicable.

BACKGROUND OF THE INVENTION

As multiplexed analytical systems continue to be miniaturized in size, expanded in scale, and increased in power, the need to develop improved systems capable of such functionality becomes more important. For example, in optical analyses, increasing multiplex often poses increased difficulties, as it may require more complex optical systems, increased illumination or detection capabilities, and new reaction containment strategies. In some cases, systems seek to increase multiplex by many fold, and even orders of magnitude, which further complicate these considerations. Likewise, in certain cases, the analytical environment for which the systems are to be used is so highly sensitive that variations among different analyses in a given system may not be tolerable. These goals are often at odds with a brute force approach of simply making systems bigger and of higher power, as such steps often give rise to even greater consequences, e.g., inter-reaction cross-talk, decreased signal to noise ratios resulting from either or both of lower signal and higher noise, and the like. It would therefore be desirable to provide analytical systems that have substantially increased multiplex for their desired analyses, and particularly for use in highly sensitive reaction systems, and in many cases, to do so while minimizing negative impacts of such increased multiplex.

Conventional optical systems employ complex optical trains that direct, focus, filter, split, separate, and detect light to and from the sample materials. Such systems typically employ an assortment of different optical elements to direct, modify, and otherwise manipulate light entering and leaving a reaction site. Such systems are typically complex and costly and tend to have significant space requirements. For example, typical systems employ mirrors and prisms in directing light from its source to a desired destination. Additionally, such systems may include light-splitting optics such as beam-splitting prisms or diffraction gratings to generate two or more beams from a single original beam.

Alternatives to the conventional optical systems have been described, in particular, alternative systems having integrated optical components designed and fabricated within highly confined environments. There is, however, a continuing need to increase the performance of analytical systems, and to improve the transmission of optical energy through waveguides. There is also a continuing need to provide improved alignment between optical sources and target waveguide devices, in particular in integrated analytical devices comprising these components.

BRIEF SUMMARY OF THE INVENTION

The present disclosure addresses these and other needs by providing in one aspect systems for optical analysis, the system comprising:

an optical source, the optical source configured to emit a broadband, multi-longitudinal optical excitation beam into free space, and

a removable target waveguide device, comprising:at least one optical coupler, the at least one optical coupler configured to receive the optical excitation beam through free space from the optical source;at least one optical waveguide, the at least one optical waveguide comprising a first end; wherein the first end of the optical waveguide is configured to receive an optical excitation signal from the at least one optical coupler;at least one reaction region, the at least one reaction region optically coupled to the at least one waveguide; andat least one detector region, the at least one detector region configured to detect an optical emission signal from the at least one reaction region.

In some embodiments of these systems, the target waveguide device further comprises:at least one optical splitter;

wherein the at least one optical splitter comprises an optical input and a plurality of optical outputs, wherein the optical input of the at least one optical splitter is optically coupled to the at least one optical coupler; and

wherein the first end of the optical waveguide is configured to receive the optical excitation signal from the at least one optical coupler, through the optical input of the at least one optical splitter, and through a first optical output of the at least one optical splitter.

More specifically, in some of these systems, the at least one optical splitter comprises from 2 to 512 optical outputs.

In some system embodiments, the at least one optical waveguide comprises a second end; wherein the second end of the at least one optical waveguide is configured to receive the optical excitation signal from the optical source.

In more specific systems, the target waveguide device further comprises:at least one optical splitter;

wherein the at least one optical splitter comprises an optical input and a plurality of optical outputs, wherein the optical input of the at least one optical splitter is optically coupled to the at least one optical coupler; and

wherein the first end of the at least one optical waveguide is configured to receive the optical excitation signal from a first optical output of the at least one optical splitter, and the second end of the at least one optical waveguide is configured to receive the optical excitation signal from a second optical output of the at least one optical splitter.

In even more specific embodiments, the at least one optical splitter comprises from 2 to 512 optical outputs.

In alternative embodiments, the target waveguide device comprises:a first optical coupler and a second optical coupler,

wherein the first end of the optical waveguide is configured to receive the optical excitation signal from the first optical coupler, and the second end of the optical waveguide is configured to receive the optical excitation signal from the second optical coupler.

According to another aspect, the disclosure provides target waveguide devices, comprising:

at least one optical coupler, the at least one optical coupler configured to receive an optical excitation beam through free space from an optical source;

at least one optical splitter, the at least one optical splitter comprising an optical input and a plurality of optical outputs, wherein the optical input of the optical splitter is optically coupled to the at least one optical coupler;

at least one optical waveguide, the at least one optical waveguide comprising a first end and a second end, wherein the first end of the at least one optical waveguide is configured to receive an optical excitation signal from a first optical output of the at least one optical splitter, and the second end of the at least one optical waveguide is configured to receive the optical excitation signal from a second optical output of the at least one optical splitter;

at least one reaction region, the at least one reaction region optically coupled to the at least one optical waveguide; and

at least one detector region, the at least one detector region configured to detect an optical emission signal from the at least one reaction region.

In specific embodiments, the devices comprise a single optical coupler for delivering the optical excitation signal to the first end and the second end of the at least one optical waveguide.

In other specific embodiments, at least one optical splitter comprises from 2 to 512 optical outputs.

In another aspect are provided systems for optical analysis, the systems comprising:

an optical source, the optical source configured to emit an optical excitation beam into free space, and

a removable target waveguide device, comprising:at least one optical coupler, the at least one optical coupler configured to receive the optical excitation beam through free space from the optical source;at least one optical waveguide, the at least one optical waveguide comprising a first end; wherein the first end of the optical waveguide is configured to receive an optical excitation signal from the at least one optical coupler;at least one reaction region, the at least one reaction region optically coupled to the at least one waveguide; andat least one detector region, the at least one detector region optically coupled to the at least one reaction region and configured to detect an optical alignment signal from the at least one reaction region;

wherein either the target waveguide device or the optical excitation beam is movable relative to other; and

wherein the system is configured to monitor the optical alignment signal and to move either the target waveguide device or the optical excitation beam relative to one another to increase the optical alignment signal.

In some embodiments, the system does not include an alignment camera.

In other embodiments, the system is configured to move either the target waveguide device or the optical excitation beam relative to the other to increase the optical alignment signal to a maximum level.

In yet other embodiments, either the target waveguide device or the optical excitation beam is movable in two dimensions.

In some system embodiments, the at least one detector region is configured to detect both an optical alignment signal and an optical emission signal from the at least one reaction region.

In other system embodiments, the optical excitation beam is configured to project at least a coarse illumination spot and a fine illumination spot on the target waveguide device, and wherein the coarse illumination spot is larger than the fine illumination spot. More specifically, the optical excitation beam is configured to project the coarse illumination spot on the target waveguide device while the target waveguide device or the optical source is moved.

In some system embodiments, the target waveguide device further comprises at least one auxiliary alignment sensor or at least one auxiliary alignment coupler positioned on a surface of the target waveguide device at a distance from the at least one optical coupler. More specifically, the distance is defined using photolithography during manufacture of the target waveguide device, or the at least one auxiliary alignment sensor or the at least one auxiliary alignment coupler is configured for use in a coarse alignment process, or the target waveguide device comprises a plurality of auxiliary alignment sensors or a plurality of auxiliary alignment couplers. Even more specifically, the plurality of auxiliary alignment sensors or the plurality of auxiliary alignment couplers are arranged in a geometric pattern, such as a geometric pattern that includes the at least one optical coupler that is optically coupled to the at least one reaction region.

In some system embodiments, the target waveguide device comprises at least one alignment feature at a defined location on the device, and wherein the location of the alignment feature is stored in a readable format on the device. In other system embodiments, the system comprises at least one optical element positioned between the optical source and the target waveguide device, wherein the at least one optical element modulates the optical excitation beam between the optical source and the target waveguide device, for example wherein the at least one optical element is a lens, a polarizer, a wedge, a filter, a prism, a mirror, or a grating.

In another aspect, the disclosure provides methods for using all of the above systems and devices.

For example, in some embodiments, the disclosure provides methods for alignment of an optical source with a target waveguide device comprising the steps of:

providing a system for optical analysis, the system comprising:an optical source, the optical source configured to emit an optical excitation beam into free space, anda removable target waveguide device, comprising:at least one optical coupler, the at least one optical coupler configured to receive the optical excitation beam through free space from the optical source;at least one optical waveguide, the at least one optical waveguide configured to receive an optical excitation signal from the at least one optical coupler;at least one reaction region, the at least one reaction region optically coupled to the at least one waveguide; andat least one detector region, the at least one detector region optically coupled to the at least one reaction region and configured to detect an optical alignment signal from the at least one reaction region;wherein either the target waveguide device or the optical excitation beam is movable relative to one another;

monitoring the optical alignment signal; and

moving either the target waveguide device or the optical excitation beam relative to one another to increase the optical alignment signal.

In yet another aspect, the disclosure provides systems for optical analysis, the systems comprising:

an optical source, the optical source configured to emit an optical excitation beam into free space,

a removable target waveguide device;wherein the target waveguide device comprises:at least one optical coupler, the at least one optical coupler configured to receive the optical excitation beam through free space from the optical source; andat least one optical waveguide, the at least one optical waveguide comprising a first end; wherein the first end of the optical waveguide is configured to receive an optical excitation signal from the at least one optical coupler; and

at least two translating lenses positioned between the optical source and the removable target waveguide device; wherein the translating lenses control delivery of the optical excitation beam from the optical source to the target waveguide in multiple directions.

Specifically, in some system embodiments, delivery of the optical excitation beam to the target waveguide device is controlled along a first direction, a second direction, and a first angle.

In some embodiments, the at least two translating lenses comprise a collimator lens and an objective lens, and more specifically, wherein translation of the collimator lens relative to the objective lens modulates delivery of the optical excitation beam to the target waveguide device along a first angle, or wherein translation of the objective lens in a first spatial direction relative to the target waveguide device modulates delivery of the optical excitation beam to the target waveguide device along a first spatial direction.

In some embodiments, translation of the objective lens in a first spatial direction and a second spatial direction relative to the target waveguide device modulates delivery of the optical excitation beam to the target waveguide device along a first spatial direction and a second spatial direction.

In still another aspect are provided systems for optical analysis, the systems comprising:

an optical source, the optical source configured to emit an optical excitation beam into free space,

a removable target waveguide device;wherein the target waveguide device comprises:at least one optical coupler, the at least one optical coupler configured to receive the optical excitation beam through free space from the optical source; andat least one optical waveguide, the at least one optical waveguide comprising a first end; wherein the first end of the optical waveguide is configured to receive an optical excitation signal from the at least one optical coupler;

a first translating lens positioned between the optical source and the removable target waveguide device; and

a first eccentric cam; wherein the first eccentric cam controls the position of the first translating lens in a first direction.

In embodiments, the first eccentric cam is driven by a first stepper motor, more specifically wherein the first stepper motor is stationary.

In other embodiments, the first eccentric cam controls the position of the first translating lens through a first stage attached to the first translating lens, or the first lens has a travel of at most 10 mm, or the first lens has a motion resolution of at least 1 μm.

In some embodiments, the system further comprises a second eccentric cam, wherein the second eccentric cam controls the position of the first translating lens in a second direction, more specifically wherein the second direction is orthogonal to the first direction or wherein the second eccentric cam is driven by a second stepper motor, and even more specifically wherein the second stepper motor is stationary, and in particular, wherein movement of the second eccentric cam does not affect the position of the first translating lens in the first direction. In specific embodiments, the second eccentric cam controls the position of the first translating lens through a second stage attached to the first translating lens.

Some system embodiments further comprise a third eccentric cam, wherein the third eccentric cam controls the position of a second translating lens, and more specifically further comprise a fourth eccentric cam, wherein the fourth eccentric cam controls the position of the second translating lens, in particular, wherein the first translating lens is a collimator lens and the second translating lens is an objective lens.

